4. You were offered kidneys from a 53-year-old male DBD (donor after brain stem death) donor who suffered from SAH (grade 5) complicating cerebral aneurysm. His retrieval S Cr was 78 µmol/L. Virology was reported as follows: HBsAg positive, HBsAb negative, HBcAb negative, both HBeAg and HBeAb are negative. Both HCV and HIV are negative.
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
What is your differential diagnosis?
How would you manage this case?
156 Comments
Murad Hemadneh
Will you accept this DBD donor?
According to the guidelines of the British Transplantation Society, kidneys from HBsAg positive donors can be used for any recipient after assessing the risks and benefits. Therefore, considering the recipient’s urgent need for a transplant, such as poor vascular access, uremia despite hemodialysis, or poor tolerability for dialysis, accepting this DBD donor seems appropriate. However, it is important to note that this donor should not be used if the recipient is co-infected with HBV and HDV.
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
If the recipient of the liver transplant is also HBsAg positive, it is possible to accept a live donor who is HBsAg positive as well. However, certain conditions need to be met. The recipient should be prescribed antiviral medications to control HBV replication after the transplant. It is important to note that there is a high risk of HBV reactivation, so even HBsAg positive patients who did not require antivirals before the transplant should start taking antiviral medications (such as tenofovir or entecavir) at the time of the transplant and continue taking them indefinitely, regardless of HBV DNA levels.Regular monitoring of liver enzymes and HBV DNA should be conducted every 3 to 6 months, and an abdominal ultrasound should be performed every 6 months.
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management? What is the differential diagnosis? How would you manage this case?
If the donor tests positive for HBsAg, HBeAg, and HBeAb, I would still accept the donor for liver transplantation if the recipient urgently needs the transplant due to specific circumstances.
The treatment protocol for the recipient remains the same in this scenario.
The recipient should receive Hepatitis B Immunoglobulin (HBIG) along with antiviral drugs (Tenofovir or Entecavir) as prophylactic treatment for HBV, particularly if they have non-protective anti-HBsAb titres or if the HBV DNA status of the donor is unknown.
If the recipient is already immune to HBV, post-transplant antivirals may not be necessary, but close monitoring is important, and antivirals should be initiated if HBsAg appears.
Regular monitoring of liver enzymes, HBsAg, and HBV DNA should be conducted every three months for at least one year post-transplant, and subsequently based on test reports.
This donor after DBD can be accepted only if there is history indicative of HBV.
However according to current guidelines accepting such kidneys from donors with positive hepatitis B surface antigen (HBsAg) is still debatable. Yet many suggest that these organs be discarded.
Provided that the recipient has positive history of vaccination or proper previous immune response this transplantation only after patient counselling, approving to administer chemoprophylaxis prior to transplantation.
Exclusion of any abnormalities of liver function test, history of liver disease, not habitant of endemic areas of HBV.
Special consideration to the fact that fulminant hepatitis B infection had been reported in a naïve recipient who received kidneys from donors with HBsAg (+)/HBeAg (+) donors
Recipient ought to accept administration long term prophylaxis with antiviral prophylaxis with tenofovir or entecavir can be given as well as checking the affordability of treatment from the insurance besides being counselled about risk of de novo infection.
Regular frequent post-transplant monitoring of Liver enzymes and HBV PCR should be done every 3 months in year 1 and during periods of heavy immunosuppression.
Multidisciplinary team including hepatologists as well as the need to consider their opinion for fibroscan prior to transplantation and exclusion of HCC or liver cirrhosis.
Other hepatotropic viruses screening should be performed.
I would not accept donors confirmed to be HBV positive. Hepatitis B e antigen (HBeAg) and hepatitis B e antibody (anti-HBe) positivity are indicative of viral replication and infectivity.
Differential diagnosis include the following:
Early stage of HBV infection or HBV and HDV co-infection or false positive HBsAg.
Further management:
Other hepatotropic viruses, liver enzymes, ultrasound screening should be performed.
Antiviral prophylaxis with tenofovir or entecavir can be given as this recipient is only HBcAb positive.
Regular frequent post-transplant monitoring of Liver enzymes, HBsAg and HBV PCR should be done every 3 months in year 1 and during periods of heavy immunosuppression.
Multidisciplinary team including hepatologists as well as the need to consider their opinion for vaccination.
Optimization of immunosuppressive regimen as well as avoidance of B and T cell depleting agents if possible.
the given donor is a SCD after brain death due to SAH….there is normal renal function of the donor….the donor is HbsAg positive…. other serological tests like anti HbsAb, HbcAb, HBeAg are negative…It signifies Chronic Hepatitis B infection.. There is no active infection in the donor as HbeAg is negative….As per the BTS guidelines kidneys from HBsAg positive donors can be used for any recipient after the risk benefit assessment…It is useful to accept the kidney to a recipient who is on the waiting list for a long time with vascualr access failure and in whom the life expectancy on dialysis isn short….the recipient should be counselled for the risk of acquiring the HBV infection…the risk of infection from HbsAg positive donor is higher than risk from HBcAb positive recipient…The recipient immune system should be checked for anti HBS titre and history of prior vaacination… It would be useful if the donor HBV DNA is avaialble and it is nnot available in this history… If the recipient is immune to HBV (anti HBs titre >100 IU/ml), there is no need for anti viral treatment in the recipient…but he requires regualr monitoring of HBV DNA levels 1 week, 2 weeks, 3 weeks and then monthly after transplant…If the donor HBV DNA is not known or if the recipient is not vaccinated or if the patients are not immune, recipient should receive antivirals namely tenofovir or lamivudine for 6 months with rigorous monitoring of the viral load…there are few recommendations to suggest that HBVIG to be used in addition to antivirals if the recipient are not immune when there is a HBsAG positive donor, but the use of IVIG may fear immunomodulation and graft rejection
.
will you accept this donor as a live donor if the recipient is also HbSAg positive ?
Yes HBsAg positive donor organs can be transplanted to HbsAg positive recipients.. The only condition is the the recipient should be started on anti virals soon after transplant and they should conitnue this for 6 months to 1 year as there is high risk of reactivation of HbsAg after renal transplant….irrespective of HBV DNA level the patient should be started on antivirals ..there should be monitoring of the liver function regularly after transplant
Assuming the donor is positive for HbsAg, HbeAg and HbeAb this indicated acute on chronic infection..There is high chances off disease transmission to the recipient. But as per the BTS guidelines and KDIGO guidelines, HbsAg positive donors can be transplanted irrespective of the recipient status..If the recipient is not immune to HBV before by vaccination, this patient is at highest risk of acquiring HBV and should receive antivirals and HBIG after transplant…If the recipient is in dire need for the kidney he may accept this risk rather than waiting on hemodialysis with poor life expectancy and poor vascular access…
if the recipient is positive for HbeAg, HbeAb, HbsAg it indicates that the patient has underlying acute or chronic hepatiis b with active infection…patient should be monitored for viral load, cirrhosis of liver and may have features of parenchymal damage..
☆ Transplanting an HBsAg-positive allograft into an HBsAg-negative recipient carries a significant risk of de novo infection .
☆ Transplantation of HBsAg-positive kidneys into HBV-naïve recipients may result in primary infection of the recipient, who may achieve long-term HBV suppression with NA antiviral drugs (entecavir and tenofovir), which prevents progression to cirrhosis and liver failure
☆ However, these patients remain at higher risk for hepatocellular carcinoma
● Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
☆ Kidney transplantation from HBsAg-positive donor kidneys may be safely allocated in HBsAg-positive recipients. All transplant recipients should undergo prophylaxis with lamivudine or, in case of failure, with adefovir or entecavir, which can confer long-term survival benefits
☆ Kidney transplantation in HBsAb-positive recipients with an anti-HBs titer of at least >10 IU/L could be performed safely with post-transplant HBV monitoring and, eventually, with the use of antivirals to prevent the risk of hepatitis B progression. In this setting, there appears to be no adverse impact on graft or patient survival.
☆ Transplantation of a non-liver solid organ from an HBsAg positive donor to a non-immune recipient will result in chronic infection of the recipient. In this setting, antivirals should be given to prevent HBV-related liver damage
● Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
☆ So this donor has fulminate infection and he will not be acceptable for donation
● What is your differential diagnosis?
Other concomitant virus hepatitis as HDV
● How would you manage this case?
☆ Evaluated recipient for full HBV serology
HBs Ag, HBs Ab, HBc Ab , HBe Ag, HBe Ab, PCR (HBV), PCR ( HCV), PCR ( HIV )
☆ Well vaccination for recipient
☆ Antiviral prophylaxis
☆ HBIG
☆ Monitoring for reactivating HBV or de novo infection
● Assume that the potential recipient is not desperate for a kidney from HsAg positive titre and also HeAg. Will still go ahead and accept this infected organ?
☆ In this situation I will go ahead after discussing the effects of this transplantation with the recipient ( the high risk of transmission the HBV and it’s morbidity ( graft failure and increased mortality
☆ In case of living donor I will treat him before transplantation
☆ Recipients with anti HBs Ab > 10 must receive antiviral prophylaxis with or without HBIG
☆ If HBs Ab < 10 he needs both antiviral prophylaxis and HBIG .
● Regarding a life donor with HsAg positive. What are the kidney diseases that could happen due to HBV infection?
** Renal vasculitis due to HBV related PAN
** MPGN
** Membranous nephropathy
** IgA nephropathy
References:
1) .Guidelines for Hepatitis B & Solid Organ Transplantation. BTS. March 2018.
2) .Massimiliano Veroux,Vincenzo Ardita, Daniela Corona, Alessia Giaquinta, Burcin Ekser, Nunziata Sinagra, Domenico Zerbo, Marco Patanè, Cecilia Gozzo, and Pierfrancesco Veroux1 .Kidney Transplantation From Donors with Hepatitis B . Med Sci Monit. 2016; 22: 1427–1434.
Q1: if the patient was remaining on the waiting list for a long time and there is not good vascular access, yes, however, should explain the situation and evaluate risks/benefits and start antiviral therapy and HBIg. complete the vaccination if low titer HBS Ab.
Q2: after the exclusion of HDV infection, the transplant could be performed but the recipient should take prophylaxis with tenofovir or entecavir until HBS DNA became negative but there is no need for HBIg. Q3: in this situation, there is a high risk of transmission and there is a need to receive both antiviral and HBIg. Q4: ΔΔ includes HBV and HDV co-infection or early stage of HBV.HBS infection transmission and needs antiviral prophylaxis and close monitoring and hepatologist consultation.
Q5: In this condition, recipient should know about the probability of HBS infection transmission and needs antiviral prophylaxis and close monitoring and hepatologist consultation.
Deceased donor with HBsAg positive, HBs-AB negative, HBc-Ab negative, HBe-Ag and Ab were negative, HCV and HIV negative. I won’t accept this donor as utilizing kidneys from donors with positive hepatitis B surface antigen (HBsAg) [HBsAg (+)] remains controversial, and it is generally suggested that such organs be discarded unless the recipient has HBsAg positive or anti-HBs AB positive>10 IU/ml which indicate immunity in this condition the donor would be accepted in case of desperate need for the organ . KT from living HBsAg (+) donors can be donated to anti-HBs (+) recipients with protection who have no abnormalities of liver function test, no history of liver disease within the previous 28 days, and who are not living in the area of possible mutation strain of HBV. It is important to note that fulminant hepatitis B infection had been reported in a naïve recipient who received kidneys from donors with HBsAg (+)/HBeAg (+) donors Recipient should receive long term prophylaxis with lamivudine and to be counselled about risk of de novo infection . Will you accept this as a living donor if the recipient is also HBsAg positive? If yes what are the condition that you should met? Yes I will accept him. – For both donor and recipient : Liver function, AFP and imaging including fibroscan should be done to fully evaluate hepatic state and exclude cirrhosis and HCC . -complete virology profile (HBV-DNA , HBeAG….) – antiviral treatment should start for both of them. – vaccination to recipient to protect against fulminant hepatitis Assume both HeAg and HBeAb are positive. Will this change your management? Hepatitis B e antigen (HBeAg) and hepatitis B e antibody (anti-HBe) are additional tests to identify viral replicative activity as HBeAg positivity which indicates active viral replication (i.e., usually a viral load > 10000 IU/mL). In contrast, anti-HBe positivity indicates the presence of the non-replication phase (i.e., a viral load < 10000 IU/mL).
so donor with positive HBVeAg carries a high risk of infectivity, so he is not accepted Management:
– full screening of virology in both donor and recipient. -hepatologist consultation about the risk of infection transmission and future risk of HCC. -receive either prophylaxis with vaccine and antiviral regimens. – frequent monitoring for HBV every three months in the first year and thereafter every six months.
References Guidelines for Hepatitis B & Solid Organ Transplantation, British Transplantation Society Guidelines, March 2018 First Edition Praopilad Srisuwarn et al, Kidney transplant from donors with hepatitis B: A challenging treatment option. August 27, 2021 Volume 13 Issue 8
If need demands, HBsAg positive donor can be used for any recipient, after an individualised assessment of risk and benefit.
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
– Yes, i would accept this donor as a live donor if the recipient is also HBsAg positive.
– Antivirals should be used as long as possible to suppress HBV after transplantation. Regular monitoring of HBV DNA & SGPT. In this setting, there appears to be no adverse impact on graft or patient survival.
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
No change regarding management if DBD donor is positive for HBsAg, HBeAg & HBeAb. I would accept this donor though the risk of infection is high if need demands and after individualized assessment of risk & benefit.
Antivirals (entecavir or tenofovir) from the time of transplantation and regular monitoring of HBV DNA & LFT.
What is your differential diagnosis?
– Early stage of HBV infection
– HBV and HDV coinfection
– False positive HBsAg
How would you manage this case?
– Counselling the recipient regarding chronic HBV infection, liver failure, graft failure, drug complication & death.
– Refer for hepatology consultation.
– HBV vaccination
– Antiviral from the time of transplantation
– Monitoring of LFT, HNV DNA
Yes,I will accept this donor.HBsAg positive is not a contraindication to donation.
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
yes,i will accept.Presence or absence of cirrhosis and complications of portal hypertension if presenent should be noted.The presence of chronic HBV infection, including in patients with compensated cirrhosis (ie, without complications and no evidence of portal hypertension), is not a contraindication to kidney transplantation. Antiviral therapy has been shown to reduce the risk of HBV reactivation associated with the use of immunosuppressive therapy, with improvements in survival approaching that of HBsAg-negative kidney transplant recipient.By contrast, those with decompensated cirrhosis and portal hypertension may be considered for combined liver and kidney transplantation.
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
Main concern here is Hepatitis B reactivation .Hepatitis B e antigen (HBeAg) status and HBV DNA level prior to transplantation do not reliably predict the occurrence or timing of subsequent HBV reactivation.(Among HBsAg-positive patients, reactivation of HBV replication is generally defined by the appearance of HBV DNA in a patient who has had undetectable HBV DNA previously or by a >1 to 2 logarithmic (10- to 100-fold) increase in HBV DNA.) .There is High risk of reactivation when transplantation done in HbsAg Positive patient but my managment will be same whether or not he is HBeAg positive or not.Recipient will need life long antiviral in either case.Monitoring may be done more frequently .
What is your differential diagnosis?
Chronic hepatitis B
How would you manage this case?
Antiviral therapy has been shown to reduce the risk of HBV reactivation associated with the use of immunosuppressive therapy, with improvements in survival approaching that of HBsAg-negative kidney transplant recipients. Lifelong Antiviral needed.
For most kidney transplant recipients who require antiviral therapy to prevent HBV reactivation/infection, preferred antiviral regimens include entecavir and tenofovir. We typically administer Entecavir since it is not associated with kidney toxicity; dose adjustments are required for those with reduced kidney function If tenofovir is used, we generally prefer Tenofovir alfaenamide to tenofovir disoproxil because it is associated with a lower risk of kidney toxicity.Entecavir and tenofovir are preferred over mivudinela , which had previously been the mainstay of treatment, because lamivudine has been associated with a high rate of drug resistance with long-term use.
Assume that the potential donor is not desperate for a kidney from HsAg positive and also HeAg. Will still go ahead and accept this infected organ?
I will not accept as this highly infectious with seroconversion condition with active disease.
If recipient is enthusiastic than I will inform the pros and cones.
Will consider IVIG. Regarding a life donor with HsAg positive. What are the kidney diseases that could happen due to HBV infection?
There is possibilities of polyarthritis nodosa, MPGN, MNG, treatment related MCD, FSGS.
I will accept only if the donor HBV DNA was negative by PCR , and the patient must be informed of the risk of HBV infection and the risk of graft loss.
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
Yes I will accept but before transplanting the viral load for both the donor and recipient should be suppressed and the recipient receives vaccines and antiviral therapy before and after transplantation.
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
No, this is highly infective condition.
What is your differential diagnosis?
Chronic active hepatitis
Co infection with HDV
Infections with other hepatitis viruses like A,C,and E.
How would you manage this case?
Consultation for GIT specialist , antiviral for 6 months , regular monitoring of graft function and HBV PCR monthly during the first year post transplant. Reference
BTS guidelines 2018.
As per BTS guidelines kidney of the HBsAg positive donor can be used for any recipient, after an individualised assessment of risk and benefit, with Lamivudine prophylaxis for six months after transplantation, although the risk of transmission is very low. (2C) Lots of literature described favourable outcome of HBsAg positive kidney donated to HBV immune recipients. Chronic HBV infection was infrequent outcome in most of cases where antiviral prophylaxis used (at least for short period). Yes, this DBD kidney is acceptable, if – falls into standard immunological risk (HLA, X matching and DSA) – the donor HBV DNA PCR is negative, – the recipient agrees after proper counselling – the recipient has been immunized against hepatitis-B (vaccinated with adequate HBsAb). Proper counselling of the risks of HBV infection, need for antiviral prophylaxis and long-term monitoring; marginal risk of graft failure, liver failure, and mortality, should be explained.
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
Yes, HbsAg positive donor can donate kidney to HbsAg positive recipient. In that case, donor HBV DNA has to be suppressed (undetectable with SVR) by using antivirals before transplant and recipient has to be placed on antivirals post-transplant. The risk of reactivation and CHB is moderate to high, and needs life-long antiviral and monitoring. Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management? This indicates high risk of infectivity, so donation should be deferred. What is your differential diagnosis? Co-infection with HDV infection Chronic active hepatitis B infection Acute on chronic (hepatitis A, E and C) How would you manage this case? Hepatologist consultation – involvement on treatment decision The recipient should be counselled in detail about the risks Immunization status (HBsAb >10IU/ml) should be ensured, else vaccination series be repeated. – If the recipients antiHBs is < 10 and is receiving HBsAg +/ HBeAg + donor kidney, it carries the highest risk of seroconversion àHBIG +Antiviral has to be administered Antivirals (entecavir or tenofovir) should be started immediately after transplant, continued for at least 1 year Steroid should be minimized (or avoided, if possible), Tac dose to be kept minimum allowed. Close monitoring of PCR for HBV DNA, LFTs, RFT and Tacrolimus drug level
References: 1. British Transplantation Society Guidelines: Guidelines for Hepatitis B & Solid Organ Transplantation 2018. 2. Yap DY, Tang CS, Yung S, et al. Long-term outcome of renal transplant recipients with chronic hepatitis B infection-impact of antiviral treatments. Transplantation 2010; 90:325 Dear All
Assume that the potential recipient is not desperate for a kidney from HsAg positive titre and also HeAg. Will still go ahead and accept this infected organ?
Regarding a life donor with HsAg positive. What are the kidney diseases that could happen due to HBV infection?
Please substantiate your answer. Reply to Prof Halawa’s questions If the patient is not desperate, it is better to decline the donor benefit of transplant vs waiting on dialysis for the next negative donor out ways the risk of transmission HBV infection, antiviral and its side effects, potential graft failure, morbidity and mortality. 2- What are the kidney diseases that could happen due to HBV infection?
The kidney diseases associated with HBV infection include: most commonly: Membranous nephropathy, MPGN and polyarteritis nodosa (PAN). Membranous glomerulonephritis Other less common: Mesangial proliferative glomerulonephritis, IgA Nephropathy, FSGS, Minimal Change Disease and Amyloidosis. References: · Lai KN, Lai FM. Clinical features and the natural course of hepatitis B virus-related glomerulopathy in adults. Kidney Int Suppl 1991; 35:S40. · Johnson RJ, Couser WG. Hepatitis B infection and renal disease: clinical, immunopathogenetic and therapeutic considerations. Kidney Int. 1990 Feb;37(2):663-76. doi: 10.1038/ki.1990.32. PMID: 1968522 · Shah AS, Amarapurkar DN. Spectrum of hepatitis B and renal involvement. Liver International 2018; 38(1): 23-32.
This kidney carries many risks as the donor is HBsAg positive, which means active infections. The recipient should know the risk of liver disease, high mortality, and graft disease risk.
if this recipient is not desperate for this kidney, i will reject the kidney.
Another approach is to treat the donor before RTX (in the case of a living donor) with sustained HBVsAg negative for six months before considering transplantation.
Need to check for AntiHBVsAb titer, especially if the donor is HBVsAg positive.
The main risk will come from the donor who is HBsAg , HBeAg and HBe Ab were positive as this type of donor means he is having chronic active hepatitis B and carry with him infected kidney to the recipient and on this situation vaccination status of the reciepent will affect out further decision regarding to immunize the recipient with HBIG adding to antiviral therapy . Regarding a life donor with HBsAg positive. What are the kidney diseases that could happen due to HBV infection?
a) Membranous nephropathy
b) MPGN
c) Polyarteritis nodosa
d) IgA nephropathy
Will you accept this DBD donor?
Yes , but only if the donor has PCR negative and recipient agrees and has been immunized against hepatitis B i.e., either naturally or acquired and falls into standard immunological risk and counseling of the risks of infection and graft failure should be explained to the patient. Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
Yes, HbsAg positive donor can donate kidney to HbsAg positive recipient but the viral load should be suppressed with antivirals before transplant and placed on antivirals post-transplant .Also the patient should be counseled in detail about the risks of hep b related kidney diseases after transplant. However, if the recipient is HbsAg negative , then donation of HbsAg positive should not be done unless the patient he agrees to it. Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
This indicates high risk of infectivity, so donation should not be done. And donation can only be done if the recipient agrees and has been counseled about the risks related to hepatitis B infection post transplant. What is your differential diagnosis?
Co-infection with HDV infection
Chronic active hepatitis B infection
Acute on chronic(hepatitis A,E and C) How would you manage this case?
Gastroenterologist should be consulted and taken on board. The patient should be counseled in detail about the risks and should be vaccinated and patient should be placed on antivirals (entecavir or tenofovir alafenamide) immediately after transplant and close monitoring of PCR for HBV DNA along with other tests like LFTs, and graft function must
References:
1- British Transplantation Society Guidelines: Guidelines for Hepatitis B & Solid Organ Transplantation 2018.
2- Yap DY, Tang CS, Yung S, et al. Long-term outcome of renal transplant recipients with chronic hepatitis B infection-impact of antiviral treatments. Transplantation 2010; 90:325
A DBD donor with isolated HBsAg with other negative serological makes signifies a past infection and is not a contraindication for Transplantation.
If the recipient was HBV immune so he shall not receive antivirals or IVIG
But if not HBV immune he shall receive Antivirals and IVIG
Recipient shall be examined for liver enzymes, HBsAg and HBV PCR as well as ultrasound for at least the 1st year post-transplant.
If recipient is HBsAg positive, i shall accept this transplantation yet continue antivirals for life
If the Donor is HBeAg this means active viral replication and high risk of virus transmission. Tx may proceed if extreme urgency for tx with long term antivirals and IVIG
If recipient is HBeAg we shall exclude the possibility of liver affection and he may require both liver and kidney transplant
This kidney carries many risks as the donor is HBsAg positive, which means active infections. The recipient should know the risk of liver disease, high mortality, and graft disease risk.
if this recipient is not desperate for this kidney, i will reject the kidney.
Another approach is to treat the donor before RTX (in the case of a living donor) with sustained HBVsAg negative for six months before considering transplantation.
Need to check for AntiHBVsAb titer, especially if the donor is HBVsAg positive.
The main risk will come from the donor who is HBsAg , HBeAg and HBe Ab were positive as this type of donor means he is having chronic active hepatitis B and carry with him infected kidney to the recipient and on this situation vaccination status of the reciepent will affect out further decision regarding to immunize the recipient with HBIG adding to antiviral therapy .
Regarding a life donor with HBsAg positive. What are the kidney diseases that could happen due to HBV infection?
a) Membranous nephropathy
b) MPGN
c) Polyarteritis nodosa
d) IgA nephropathy
Assume that the potential recipient is not desperate for a kidney from HsAg positive titre and also HeAg. Will still go ahead and accept this infected organ?
in low endemic area – there is chance of getting a DBD with negative serology in endemic are – we can accept this with RISK FOR TRANSMISSION in recipient
FOR LIVE DONOR treatment with antiviral is given to make serology virus free and proceed with transplant
HBV associated membranous nephropathy in recipient is to be looked for
If the patient is not desperate for that offer, I prefer to decline that donor.
HBV infection is associated with the following renal diseases: include:
Commonly: Membranous nephropathy, MPGN &PAN.
Less commonly: mesangial proliferative GN, Ig AN , FSGS, MCD & amyloidosis.
References:
-Lai KN, Lai FM. Clinical features and the natural course of hepatitis B virus-related glomerulopathy in adults. Kidney Int Suppl 1991; 35:S40.
-Johnson RJ, Couser WG. Hepatitis B infection and renal disease: Clinical, immunopathogenetic and therapeutic considerations. Kidney Int. 1990 Feb;37(2):663-76.
· Will you accept this DBD donor? Yes, provided that the recipient is immuned, accepted the low risk and will receive prophylactic anti viral treatment. This is because The risk of donor-transmitted HBV infection is lower in kidney transplant recipients compared with liver transplant recipients with similar serologic marker positivity. · Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met? If donor is HB s Ag positive, before we decide to accept we have to make sure that: -There is no active liver disease in the donor, by checking liver function, HBV DNA, liver ultrasound, etc -No active renal disease related to HBV infection, like membranous nephropathy, MPGN. · How would you manage this case? Check HBV DNA in the donor, HBs Ab in recipient. Check HCV, HDV, HEV. The recipient needs to receive anti viral prophylaxis, frequent monitor of liver function test, HBV DNA. Recipient has low titer of HBs Ab <100 to consider HBV IVIG. References:
1-World J Hepatol 2021 August 27; 13(8): 853-86
Will you accept this DBD donor?
Yes, with adequate prophylaxis using Tenofovir alafenamide (TAF) or Entecavir for twelve to eighteen months and monitoring post-transplant hepatitis B viral load.
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
Yes, would procceed for treatment using Tenofovir alafenamide (TAF) or Entecavir until negative and monitoring post-transplant hepatitis B viral load.
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
In this case we have Hepatitis B activity. I would not accept the donor.
What is your differential diagnosis?
Drugs interaction, CNI toxicity, other hepatitis infections, autoimmune diseases
How would you manage this case? Since the donor is HBsAg positive, the recipient should be checked for
HBs Ag and antibodies,
HBVeAg and antibodies
HBV DNA level
If HbsAb < 10 vaccine and immunoglobullin If HBeAg is positive, do not proceed with transplantation
If HBV DNA positive should call a hepatologist or Infectologist to assure management
first will assess the recipient’s status by LFT, liver enzyme,HBAb.HBeAg, HBe Ab .HBcAb.HBDNA.
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
yes, according to the recipient should be counseled about the risk of transmission of hepatitis B .active hepatitis B in donors is usually contraindicated to living donors in kidney transplantation, however, the donation can be considered in some urgent situations such as multiaccess failure.
hepatitis sAg and HBC Ab positive if HBCAb positive if HBSAb>100iu/l and HBV DNA is not detected the infection risk of the donor is low, antiviral prophylaxis should be given(entecavir &adefovir) at least 6-12 month posttransplant and follow up every three months by HBsAg HBV DNA and liver enzyme for 1 year
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
avoid this type of donor as has an active hepatitis B infection and a high risk of transmission infection
What is your differential diagnosis?
occult hepatitis B infection or hepatitis B and HDV co-infection
If need demands, the non-liver solid organs of the HBsAg positive organ donor can be used for any recipient, after an individualised assessment of risk and benefit. (2C)
The donation of non-liver solid organs from an HBsAg positive donor to an HBsAg positive recipient can be undertaken as long as antivirals are used to suppress HBV after transplantation. In this setting, there appears to be no adverse impact on graft or patient survival.
Transplantation of a non-liver solid organ from an HBsAg positive donor to a non-immune recipient will result in chronic infection of the recipient. In this setting, antivirals should be given to prevent HBV-related liver damage.
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
Yes,,,,
Without appropriate prophylactic treatment, HBV recurrence is almost universal
Recipients with evidence of past HBV infection (HBcAb positive alone) are at risk of HBV reactivation post-non-liver transplant and could be considered for prophylactic antiviral treatment; although monitoring for HBV recurrence is an equally acceptable strategy. (2B)
There is also the precedent of using HBsAg positive kidneys in patients with HBsAb immunity, showing good graft and patient survival using a combination of HBIG and lamivudine prophylaxis .
In carefully selected patients with appropriate consent, the use of HBsAg positive donor organs may be a useful strategy to further expand the donor pool.
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
,,, chronic active hepatitis,,,, I will not accept such donor
What is your differential diagnosis?
False positive result
Co infection with HDV
Chronic HBV
How would you manage this case?
MDT including hepatologist and infectious
Recipient counseling
In first year post transplantion every three months LFT and HBV serology should be monitored
Vaccination according to HBs AB should be done
HBIG and lamivudine prophylaxis
• Individuals undergoing non-liver solid organ transplantation who are HBsAg positive must have liver disease staging and suppression of HBV DNA by either tenofovir or entecavir before transplantation if there is a standard clinical indication. (1B)
4. You were offered kidneys from a 53-year-old male DBD (donor after brain stem death) donor who suffered from SAH (grade 5) complicating cerebral aneurysm. His retrieval S Cr was 78 µmol/L. Virology was reported as follows: HBsAg positive, HBsAb negative, HBcAb negative, both HBeAg and HBeAb are negative. Both HCV and HIV are negative.
– yes, I would, due to the growing demand for organ donors
– organs from donors with HBsAg positive (active HBV infection) have a high risk of transmission resulting in primary infection hence the need for prophylaxis
– the potential recipient should also be made aware of the increased risk of disease transmission since it may actually result in graft rejection and loss
– HBsAg positive donors can safely donate to: –
HBsAg positive recipients who will need antiviral prophylaxis with entecavir
successfully immunized recipients i.e., anti-HBs titer >10 IU/ml) – such recipients do not need prophylaxis
– organs from donors who are HBsAg positive should be avoided in naïve recipients (HBsAg negative, HBcAb negative, HBsAb negative) unless the benefit outweighs the risk of post-transplant de novo hepatitis B infection
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met? (1, 3)
– yes, I would if in dire need
– the donor would need to do HBV DNA viral load
– but the recipient would need to do HBV DNA viral load, HBcAb, HBsAb, HBeAg, liver enzymes, liver fibroscan, HDV Ab, HDV RNA, HCV Ab, HIV Ab prior
– assuming the above serologies are unremarkable, the recipient should be initiated on antiviral therapy with entecavir or tenofovir (entecavir preferably) aiming for undetectable HBV DNA level i.e., virological suppression
– the recipient will need to monitor HBV DNA viral load and liver enzymes so as to assess response to treatment
– previously, lamivudine was the primary antiviral agent for chronic HBV before and after transplant
– currently, entecavir and tenofovir are preferred/ superior to lamivudine since they have a high genetic barrier to resistance and as such have very low resistance rates
– entecavir and tenofovir are highly potent nucleos(t)ide analogs which are safe and effective and are given once daily orally
– however, if we have elevated HBV DNA levels, positive HBeAg, negative HBsAb: avoid transplantation due to the high risk involved
– if the recipient has features of liver cirrhosis consider a liver and kidney transplant
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management? (1)
– in this case, the priority is to treat the active infection since this is a highly infectious patient
– check HBV DNA levels, HBsAb, HBcAb IgM IgG
– offer antiviral therapy, HBIG can be considered if there is no response to treatment with antiviral therapy
– once virologically suppressed then we can consider donation
– HBeAg and HBeAb tests are used to identify viral replicative activity
– a positive HBeAg indicates active viral replication usually a viral load >10,000 IU/ml
– on the other hand, a positive HBeAb indicates the presence of a non-replication phase i.e., viral load <10,000 IU/ml
– HBsAb is a marker of immune status as a result of either naturally-acquired or vaccine-acquired immunity
– NAT (nucleic acid test) for HBV, HCV and HIV – it is done to improve the sensitivity of screening tests, it has been proposed as an optional screening test among donors
What is your differential diagnosis?
– HBV reactivation
– Past infection
– False positive HBsAg
– HBV/ HDV coinfection
How would you manage this case?
– multidisciplinary approach: engage a hepatologist, infectious disease specialist
– recipient would need to do HBV DNA viral load, HBcAb, HBsAb, HBeAg, HDV Ab, HDV RNA, liver enzymes, liver fibroscan, HCV Ab, HIV Ab prior
– the patient should be initiated on antiviral therapy with entecavir or tenofovir (entecavir preferably) aiming for undetectable HBV DNA level i.e., virological suppression
– monitor HBV DNA PCR viral load to assess response to therapy
– HBIG can be considered if there is no response to antiviral therapy
References
1. Srisuwarn P, Sumethkul V. Kidney transplant from donors with hepatitis B: A challenging treatment option. World journal of hepatology. 2021 Aug 27;13(8):853-67. PubMed PMID: 34552692. Pubmed Central PMCID: PMC8422915. Epub 2021/09/24. eng.
2. Huprikar S, Danziger-Isakov L, Ahn J, Naugler S, Blumberg E, Avery RK, et al. Solid organ transplantation from hepatitis B virus-positive donors: consensus guidelines for recipient management. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2015 May;15(5):1162-72. PubMed PMID: 25707744. Epub 2015/02/25. eng.
3. Song JE, Kim DY. Diagnosis of hepatitis B. Annals of translational medicine. 2016 Sep;4(18):338. PubMed PMID: 27761442. Pubmed Central PMCID: PMC5066055. Epub 2016/10/21. eng.
Will you accept this DBD donor? Yes. But only if potential recipient is very desperate. Patient counselling regarding risk of HBV infection is very important. He will need immune globulins and nucleoside analogue therapy.
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met? Yes He will be at high risk for recurrence. Combinition treatment with immune globulins and nucleoside analogue therapy will be needed from transplant time . Long term prophylaxis with lamuvidine can confer survival benefits. Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management It will be high risk case. I will check HBV DNA positivity at the time of transplant Assessment of liver functions is required. Likely chronic active phase. He should receive Hep B immune globulins and nucleoside analogue.
What is your differential diagnosis? Occult Hepatitis B infection, HDV coinfection,
How would you manage this case? Recipient need to be screened for HBsAg , HBeAg, HBeAb, HDV, HBV DNA levels Discussion with Hepatologist Counselling the patient about the risk of post transplant reactivation, Reinfection, References BTS Guidelines 2018
Will you accept this donor?
Yes, I will accept this case as potential donor. According to British society of kidney transplantation this HBV donor can be accepted as potential kidney donor but special precautions including HBeAg negative PCR and HDV PCR negative. Regarding recipient he should be vaccinated with sufficient antibodies titer at least above 10iu/ml (preferred above 100iu/ml). Will you accept this donor as alive donor if the recipient is also HBsAg positive No, donor should be healthy individual with low risk of developing ESRD and HBV is associated with cryoglobinemia and GN that’s why I will only accept this condition from deceased donor. Suppose the donor is deceased and recipient also is HBsAg positive I will accept but with special precautions because the risk of reactivation -Regarding recipient should be not of viremia at the time of transplant (PCR negative and HBeAg negative), not decompensated liver , he is already on lifelong prophylactic treatment and low immunological risk to avoid use of heavy immunosuppression induction therapy.
–Regarding donor: he should have no high viral load detected by PCR, HBeAg -ve and negative HDV Co-infection. Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
I will discard this kidney What is your differential diagnosis?
-past infection (HBVsAg – ve and HBC antibody +ve)
-chronic state (HBVs Ag +ve and HBC antibodies +ve) How would you manage this case? I will do labs for bith donor and recipient including -Donor:HDV PCR, HBVe Ag and HBV PCR
· If all positive I will reject the donor
· If all negative, I will accept the donor
· If HBV PCR positive, I will accept this graft for immune recipient with antibodies titer above 100 iu/ml or desperate non immune recipient with urgent need for transplantation (like failed vascular access) after proper counseling of the risk of transmission and post-transplant HBIg and prophylactic antiviral therapy for 1year post transplant and frequent moitoring of liver enzymes and viral load by PCR every 3 months.
· If HBVeAg or HDV PCR positive I will reject the donor. -Reciepient: HBV antibody titer
· If below 10iu/ml: revaccinated pretransplant if possible and follow up titre 4weaks if not he may need antiviral treatment with or without HBIg based on donor viral status.
· If more than 100 IU/ml go ahead for transplant with no need for revaccination but antiviral prophylactic based on donor viral status. References
1- Chan TM, Fang GX, Tang CS, et al. Preemptive lamivudine therapy based on HBV DNA level in HBsAg-positive kidney allograft recipients. Hepatology 2002; 36:1246.
2- Yap DY, Tang CS, Yung S, et al. Long-term outcome of renal transplant recipients with chronic hepatitis B infection-impact of antiviral treatments. Transplantation 2010; 90:325.
3- Liaw YF, Sung JJ, Chow WC, et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med 2004; 351:1521.
4- Loomba R, Rowley A, Wesley R, et al. Systematic review: the effect of preventive lamivudine on hepatitis B reactivation during chemotherapy. Ann Intern Med 2008; 148:519.
5- Han DJ, Kim TH, Park SK, et al. Results on preemptive or prophylactic treatment of lamivudine in HBsAg (+) renal allograft recipients: comparison with salvage treatment after hepatic dysfunction with HBV recurrence. Transplantation 2001; 71:387.
6- Chancharoenthana W, Townamchai N, Pongpirul K, et al. The outcomes of kidney transplantation in hepatitis B surface antigen (HBsAg)-negative recipients receiving graft from HBsAg-positive donors: a retrospective, propensity score-matched study. Am J Transplant 2014; 14:2814.
7- Shaikh SA, Kahn J, Aksentijevic A, et al. A multicenter evaluation of hepatitis B reactivation with and without antiviral prophylaxis after kidney transplantation. Transpl Infect Dis 2022; 24:e13751.
Will you accept this donor as a live donor if the recipient is also HBsAg positive?
If yes, what are the conditions that should be met?
The donation of non-liver solid organs from an HBsAg positive donor to an HBsAg positive recipient can be undertaken as long as antivirals are used to suppress HBV after transplantation.
Pre-transplant suppression for patients with HBsAg positive disease should be given with tenofovir or entecavir . Also can donate to immune-recipients with anti-HBs at least 10 mIU/mL is a key factor in overcoming the risk of HBV transmission.
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
Yes ,this high infectious risk donors better to be avoided.
What is your differential diagnosis?
Acute or chronic HBV infection.
How would you manage this case?
Blood tests for HBV DNA, HBe Ag, HBe AB and liver function tests should be routinely
monitored after transplantation and when there is a change of immunosuppression.
accordingly HB virus drugs can be given.
References:
1-Guidelines for Hepatitis B & Solid Organ Transplantation. BTS 2018.
Will you accept this donor? -No , I will not accept him except in emergenct situations as recipient running out of vascular access. This donor with HBsAg positive, negative ( HBsAb, HBcAb, HbeAg and HBe Ab) mostly has acute HBV infection and still in window phase and has high risk for HBV transmission ,so further risk assessment is needed including risk of HBV infection as previous blood transfusion , liver function status and HBV DNA PCR. – Will you accept this donor if living donor and recipient is also HBsAg positive? Yes , I will and start prophylactic treatment immediately after transplantation. – If yes what conditions should be met? I would prefer to give this graft toelderly recipient with no other hepatic risk factors as no fatty liver and normal liver function tests , in addition , low immunological risk so no need for heavy IS protocol . .
Yes; I would accept esp if recipient has same Hep B status or if he has Antibody titer more than 10iu/ml which would confer some immunity, thereafter 3TC prophylaxis for a long duration post transplant should be given. The recipient should have extensive counselling sessions on risks of developing de novo infection post transplant. Conversely if recipient has HBsAG -ve, unless really desperate and this is the last option I would not transplant.
Acceptance of living donor if recipient is also HBsAG +VE and the recommendations to be met;
I would transplant but use an MDT approach with a gastro brought on board to screen for poor prognostic factors in Hep B and decide on initiation of treatment ; Hep B DNA,LFTS,AFP and fibro scan to exclude cirrhosis and HCC. Ideally the recipients should have low viral loads or undetectable levels to improve prognosis post transplant. Donor should have undetectable viral loads to decrease risk of reactivation with hepatitis. Hep D coinfection does occur in Hep B pts and this too should be screened and with a PCR and ruled out. Antivirals to be considered -3TC,adefovir or entecavir.
Both HBeAG and HBeAB + VE, will this mgt change?
This predisposes recipients to high risk of severe hep B infection and as such I would not allow donor to donate.
DDX;
Acute Hep B.
Chronic Hep B
MGT.
The recipient should be investigated and risk stratified with ;HBsAG, HBsAB, HBV DNA,LFTS and treated appropriately(Antivirals, vaccination or immunoglobulin).HDV RNA too done to R/O any coinfection.
REF;
HEP B and SOT – BTS
Srisuwarn et al ;Kidney transplant from donor with Hep B;A challenging TX option.World J hEPATOL.2021aUG 27;13(8);853-867
I will accept infected kidney if recipient is desperate but should be counselling regarding transmission of disease and risk of rejection and loss graft.
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
Yes I will accept this case for transplant but should do HBV DNA viral load and HbsAb and should receive anti viral therapy with monitoring of HBV DNA
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
It’s means highly infected hepatitis B , should be treated first with anti viral therapy and receive HB immunoglobulin
What is your differential diagnosis?
Reactivated HBV
Past infection
How would you manage this case?
Serial monitoring of HBV DNA PCR and HbsAB
Start Antiviral therapy tenofovir and entecavir
👉 HBV SAg postive means active infection so HBV PCR is essential, and only used for HBV postive recipient after high risk consent , counseling about risk of activation and treatment with antiviral therapy , tenofovir is indicated
👉 we can accept. But with PCR follow up and commencing antiviral therapy.
👉 In case of postive HB eAg and antibodies, indicating active infection with high viral replication (corresponding mainly to high PCR viral titer ), it is CI to accept the donation offer.
👉 Differential diagnosis is either early acute infection or chronic HBV infection.
👉 use the offer with prophylactic vaccination or immunization until Ig reaches protective level and starting anti viral therapy with close monitoring of HBV PCR.
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
Yes, in following conditions
If both recipient develop immunity due to natural infection
If HBV DNA is documented negative and recipient is vaccinated to develop protective antibody levels.
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management? This is chronic HBV infection with persisting replicating virus. I will not accept this person as donor
What is your differential diagnosis?
Recovering infection if anti HBs is also positive
Regarding a life donor with HsAg positive. What are the kidney diseases that could happen due to HBV infection?
Membranous nephropathy
The use of HBsAg positive donor organs may be a useful strategy to further expand the donor pool.
The donation of non-liver solid organs from an HBsAg positive donor to an HBsAg positive recipient can be undertaken as long as antivirals are used to suppress HBV after transplantation.
There is a significant published literature describing the outcome of HBsAg positive kidney donation to HBV immune recipients
Therefore in this setting we should evaluate the immune status of the recipient
In the majority of cases, antiviral prophylaxis has been given after transplantation.
Will you accept this DBD donor?
Yes if the condition of the recipient is urgent for transplant. We can ,recently and depending on some expertise, go toward renal transplantation. However, HBIG and antiviral should be started. The close monitoring serology and HBV DNA should be performed routinely
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
It is preferable not to accept this patient
However, if we can’t delay renal transplantation, in this case we should perform HBV DNA for the donor
And
HBsAB for the recipient to evaluate the immune state in addition to HBsAg
A- If the recipient has HBsAb
antivirals are stopped after a period of prophylaxis, the recipient should receive long-term monitoring for the appearance of HBsAg.
B- if it is a non-immune recipient this will result in chronic infection of the recipient. In this setting, antivirals should be given to prevent HBV-related liver damage
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
A- THIS positivity indicates the activity of desease.
Then it is preferable to perform HBV DNA and Stop renal transplantation
B- If it is the case of living donation
treatment should be started before transplant.
What is your differential diagnosis?
– Early HBV infection – HDV co-infection with HBV – False positive HBsAg results
How would you manage this case?
We should inform the patient about the risk of this transplantation
We should indicate the level of risk depending
1- if the recipient has HBsAg pos or neg
2- if the recipient has HBsAb pos or neg
If the recipient had HBsAg neg or if the patient has HBsAg pos with no immune state (HBsAb neg) ==> high risk==> HBIG + antiviral
if the patient has HBsAg pos with immune state (HBsAb pos) ==> less risk==> prophylaxis antiviral
1- we have to assess the donor for HBV RNA, liver enzymes and imaging of the liver
if positive HBV RNA and elevated liver enzymes : it is acute hepatitis and I will not accept.
If negative test: it is chronic infection and can be accepted wit matching to recipient with HBs Ag positive or immunized patient after discussing with the recipient regarding the risks of transmission of infection and maintain on prophylactic antiviral drugs (provided the recipient has no HDV infection)
2- if live donor and the recipient is HBs Ag positive:
exclude the recipient concomitant HDV infection
Recipient must have liver disease staging and suppression of HBV DNA by either tenofovir or entecavir before transplantation
accept with possible transmission risk and combination therapy with HBIg and/or a potent nucleotides analogue (NA) is recommended from the time of transplantation to prevent HBV reinfection post-liver transplant.
3- both HBeAg and HBeAb are positive indicate viral replication —- I will not accept 4- DD:
acute hepatitis (elevated enzymes and positive HBV RNA)
chronic hepatitis (isolated HBs Ag)
5- Management
assess liver enzymes, HBV RNA and liver imaging in the donor
recipient evaluation for HBs Ag, HBc Ab and HDV RNA
if the donor is negative for HBV RNA: accepted
in immunized recipient: prophylactic lamuvidine for 6-12 month
in HBsAg positive recipient and negative HDV RNA:
combination therapy with HBIg and/or a potent nucleotides analogue (NA) is
recommended from the time of transplantation to prevent HBV reinfection post-
liver transplant.
Will you accept this DBD donor?
A positive HBsAg test indicates active infection and HBV carefully selected patients with
appropriate consent, the use of HBsAg-positive donor organs may be a useful strategy to
further, expand the donor pool as it could be transmitted by any organ or tissue in this setting. HBsAg-positive donors can be considered for HBsAg-positive recipients, or in exceptional
circumstances after specialist advice, informed consent, or for HBcAb-positive
recipients which Indicate a low risk of reactivation Most guidelines exclude them from donation unless the recipient is also HBs Ag positive in urgent cases. Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
He is at high risk of recurrence,
combination therapy with HBIg and/or a potent NA is recommended from the time
of transplantation to prevent HBV reinfection post-liver transplant. (1B)
so, the answer is Yes, provide the HBV DNA < 200 and rule out HDV co-infection in the recipient with the use of a combination of HBIG and lamivudine prophylaxis. Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
Need to check the HBV DNA if positive at the time of transplant,
Any evidence of HDV co-infection by HDV antibodies serology and if positive HDV serology e need to do HDV RNA testing must be performed in potential transplant recipients where HDV
serology is positive or equivocal. (1B).
What is your differential diagnosis?
occult HBV or HDV co-infection also another viral screen like HIV and HCV screen How would you manage this case? As the donor HBsAg positive need to screen the recipient with HBs Ag, HBe Ag, and AB, HDV serology, and HBV DNA level and refer to a hepatologist as part of the MDT approach with proper counseling for the recipient about the risk of Post transplantation re-infection or reactivation or eve denovo HBV infection including the risk of HBV related de nonvo nephropathies like MGN or MPGN.
I will not accept this donor as neither DBD nor living donor because it is high risk and associated with higher mortality……
waiting more better than treatment of complications
53- year DBD, HBsAg positive, HBsAB negative, HB cAb negative, HBeAg and Ab were negative, HCV and HIV negative.
1. Will you accept this deceased donor?
· Yes if the recipient is having HBsAg positive as well
If the recipient is having natural or acquired immunity (anti-HBs concentration of >10 IU/ml)
· In both conditions the recipient should receive long term prophylaxis with lamivudine or, in case of failure, with adefovir or entecavir.
· In HBV naïve recipient the risk is high, it depends on the organ demand, but still can go for transplantation.
2. Will you accept this as a living donor if the recipient is also HBsAg positive? If yes what are the condition that you should met?
Yes
· Referred to see a hepatologist to asses HepBV DNA, liver function, fibroscan/ liver biopsy, give antiviral treatment and exclude HCC.
· This patients should receive long term prophylaxis with lamivudine, with adefovir or entecavir, as this can confer long-term survival benefits.
3. Assume both HeAg and HBeAb are positive. Will this change your management?
· The acceptance of donors with HBV infection depends on risk assessment of HBV infectivity risk.
· Since this donor with HBVeAg carries a high risk of infectivity and fulminant hepatitis B infection, this donor should not be used.
Management:
· Since the donor is HBsAg positive, the recipient should be checked for HBs Ag and antibodies, HBVeAg and antibodies, and HBV DNA level and be assessed by a hepatologist if any abnormal results
· Then according to risk, the recipient should receive either prophylaxis with vaccine, HBIG, and antiviral regimens.
· Monitoring for HBV Recurrence or De Novo Infection: HBV DNA and HBsAg should be monitored every three months in the first year and thereafter every six months.
References
1. Guidelines for Hepatitis B & Solid Organ Transplantation, British Transplantation Society Guidelines, March 2018 First Edition
2. Huprikar1, et al, Solid Organ Transplantation From Hepatitis B Virus–Positive Donors: Consensus Guidelines for Recipient Management, American Journal of Transplantation 2015; 15: 1162–1172
3. Praopilad Srisuwarn et al, Kidney transplant from donors with hepatitis B: A challenging treatment option. August 27, 2021 Volume 13 Issue 8
Will you accept this DBD donor?
Yeas I will accept ,after informed the recipient about the disease and possibility of transmission and reactivation and what is role of immune supressions.
Management
First assessment of immune status of the recipient
CBC ,RFT ,LFT ,LIVER ENZYMES , HBsAg , HBsAb , HBeAg , HBeAb , HBcAb , HBV DNA ,
Investigate for co infection HDV infection.
If recipient immune and vaccinated we proceed to transplant, HBV immunoglobulin and anti viral should be started.
Monitor the recurrence with :
HBV DNA positive at time of transplant.
HBeAg positive patients.
Those transplanted for hepatocellular carcinoma.
HIV co-infected.
If recipient had no history of prior infection and not immune when donor has HBsAg positive ,the transplantation is complicated and not advice. Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
After assessment of serum ALT, HBV DNA, is it active disease and HBV DNA is high that need treatment with anti viral till HBV DNA is getting low then answer is yeas and will accept, In addition, hepatitis flare was defined by rising of serum ALT more than 3 times the baseline level and > 100 U/L with evidence of hepatitis B reactivation monitoring liver enzymes, HBsAg, and HBV DNA every 3 mo for at least 12 mo post-transplantation. Subsequent management was based on the evolution of test results over the first year.
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
No change , In patient positive HBsAg ,positive HBeAg, positive HBeAb we need to do ALT , AST to asses the active disease which need urgent treatment with antiviral for live donor to decrease the infection and lowering the transmission ,and also assessing the immune status of the recipient, if vaccinated and immune well we proceed . The transplant recipient should receive Hepatitis B Immunoglobulin (HBIG) with antivirals (Tenofovir/ entecavir) as prophylactic treatment for HBV, especially non-protective anti-HBsAb titres and if the HBV DNA status of the donor is not known. What is your differential diagnosis?
Acute viral hepatitis
Acute on chronic HBV infection
Reactivation of chronic hepatitis B References
1. BTS Guidelines for Hepatitis B & Solid Organ Transplantation, 2018
2 . Wachs ME, Amend WJ, Ascher NL, Bretan PN, Emond J, Lake JR, Melzer JS, Roberts JP, Tomlanovich SJ, Vincenti F. The risk of transmission of hepatitis B from HBsAg(-), HBcAb(+), HBIgM(-) organ donors. Transplantation. 1995;59:230–234. [PubMed] [Google Scholar]
3 . Schieck A, Schulze A, Gähler C, Müller T, Haberkorn U, Alexandrov A, Urban S, Mier W. Hepatitis B virus hepatotropism is mediated by specific receptor recognition in the liver and not restricted to susceptible hosts. Hepatology. 2013;58:43–53. [PubMed] [Google Scholar
Will you accept this DBD donor?
Normally a deceased donor who is HBsAg positive will not be accepted. However, if there is a potential recipient who has been fully vaccinated against hepatitis B and has acceptable titers of the HBsAb and has exhausted his access sites, may be considered to get the kidney after counseling and explaining the risks
Living donor:
if this was a live donor who is HbsAg positive and the recipient is also HBsAg positive, then the transplant can proceed after meeting the following criteria:
The donor should have an undetectable viral load
The recipient should have an undetectable viral load
The recipient should not have liver cirrhosis. If the recipient has liver cirrhosis, then a dual liver and kidney transplant should be considered
The recipient should get antiviral prophylaxis and the liver enzymes as well as the hepatitis B viral load should be monitored
If both HBeAg and HBeAb are positive in addition to HBsAg:
Hepatitis B e Ag is a secretory protein that is processed from the precode protein. It is an early antigen and not an envelope antigen. The presence of HBeAg is usually associated with high levels of HBV DNA and higher rates of transmission.
HBeAg to HBeAb seroconversion occurs early in patients with acute infection, prior to HBsAg to HBsAb conversion. So the presence of all three being positive could suggest that it is an acute infection and the transplant will have to be postponed to asses for HbsAg seroconversion to HBsA. So one would need to do the HBcAb. If the IgM is positive it would signify an acute infection and the transplant would need to be postponed
Assume that the potential recipient is not desperate for a kidney from HsAg positive titre and also HeAg. Will still go ahead and accept this infected organ?
Regarding a life donor with HsAg positive. What are the kidney diseases that could happen due to HBV infection?
Assume that the potential recipient is not desperate for a kidney from HsAg positive titer and also HeAg. Will still go ahead and accept this infected organ?
At this situation, I will accept the case with the following considerations
The recipient should be informed about the high risk of transmission of the virus with possibility of liver failure, graft loss and increased mortality.
Treatment of the donor and providing functional cure (sustained absence of HBsAg with or without the development of anti-HBs) before transplantation is the best option for the recipient (applicable for living donor only)
If the recipients antiHBs is < 10 and is receiving HBsAg (+)/HBeAg (+) donor kidney, this carry the highest risk of seroconversion and he/she should receive both antiviral and HBIG.
If the recipients antiHBs is≻ 10 and is receiving HBsAg (+)/HBeAg (+) donor kidney, he/she should receive prophylaxis using antiviral with or without HBIG
Regarding a life donor with HsAg positive. What are the kidney diseases that could happen due to HBV infection?
HBV related glomerulonephritis, membranous nephropathy (1) or MPGN (2) are the most common forms, less common forms includes mesangial proliferative glomerulonephritis (3), IgA nephropathy (4), MCD (5), FSGS (6) and amyloidosis (7).
Polyarteritis nodosa (PAN) (8)
References
1. Johnson RJ, Couser WG. Hepatitis B infection and renal disease: Clinical, immunopathogenetic and therapeutic considerations. Kidney Int 1990; 37:663.
2. Lai KN, Lai FM. Clinical features and the natural course of hepatitis B virus-related glomerulopathy in adults. Kidney Int Suppl 1991; 35:S40.
3. Chung DR, Yang WS, Kim SB, et al. Treatment of hepatitis B virus associated glomerulonephritis with recombinant human alpha interferon. Am J Nephrol 1997; 17:112.
4. Sun IO, Hong YA, Park HS, et al. Clinical characteristics and treatment of patients with IgA nephropathy and hepatitis B surface antigen. Ren Fail 2013; 35:446.
5. Zhou TB, Jiang ZP. Is there an association of hepatitis B virus infection with minimal change disease of nephrotic syndrome? A clinical observational report. Ren Fail 2015; 37:459.
6. Sakai K, Morito N, Usui J, et al. Focal segmental glomerulosclerosis as a complication of hepatitis B virus infection. Nephrol Dial Transplant 2011; 26:371.
7. Saha A, Theis JD, Vrana JA, et al. AA amyloidosis associated with hepatitis B. Nephrol Dial Transplant 2011; 26:2407
8. Takekoshi Y, Tochimaru H, Nagata Y, Itami N. Immunopathogenetic mechanisms of hepatitis B virus-related glomerulopathy. Kidney Int Suppl 1991; 35:S34.
If the potential recipient is not desperate to receive a kidney, then the kidneys should not be transplanted
The kidney diseases that could happen due to HBV infection include:
Q1. In case the recipient is not desperate, then there is no urgent demand and the best for us is to wait for a better kidney for a HBsAg negative recipient.
1- Assume that the potential recipient is not desperate for a kidney from HsAg positive titre and also HeAg. Will still go ahead and accept this infected organ?
If the recipient is not desperate on the HBsAg/HBeAg +ve ( high risk for reactivation), i will not proceed transplanting the infected organ to the patient.
2- Regarding a life donor with HsAg positive. What are the kidney diseases that could happen due to HBV infection?
he diseases could happen due to hepatitis B infection form a donor HBsAg +ve are:
If patient is not desperate and no urgency for transplantation, it is better to decline the donor.
The kidney diseases associated with HBV infection include:
Most commonly: Membranous nephropathy, MPGN and polyarteritis nodosa (PAN).
Other less common: mesangial proliferative glomerulonephritis, IgAN , FSGS, MCD and amyloidosis.
References: -Lai KN, Lai FM. Clinical features and the natural course of hepatitis B virus-related glomerulopathy in adults. Kidney Int Suppl 1991; 35:S40.
-Johnson RJ, Couser WG. Hepatitis B infection and renal disease: clinical, immunopathogenetic and therapeutic considerations. Kidney Int. 1990 Feb;37(2):663-76. doi: 10.1038/ki.1990.32. PMID: 1968522.
1: I will not accept a kidney from a donor with active viral HBV in replication.
As long as there is no emergency, the risk-benefit is that I will not expose the recipient to this high risk of transmission of infection.
2- What are the kidney diseases that could happen due to HBV infection? Renal diseases resulting from HBV infection are membranous glomerulonephritis, membranoproliferative glomerulonephritis (MPGN), Polyarteritis nodosa (PAN), mesangial proliferative glomerulonephritis, IgA nephropathy, and amyloidosis.
Shah, A. S., & Amarapurkar, D. N. (2018). Spectrum of hepatitis B and renal involvement. Liver International, 38(1), 23-32.
Eckardt, K. U., Kasiske, B. L., & Zeier, M. G. (2009). KDIGO clinical practice guideline for the care of kidney transplant recipients. American Journal of Transplantation, 9, S1-S155.
No; -If recipient is not desperate for kidney from doner who is HBsAg positive and also HBe Ag (high risk for infection), and without informed consent for acceptance the risk for HBV infection and for acceptance for life-long combination therapy with HBIG and a potent NA can potentially be given to this patient. -So as no urgency, I will not accept this infected organ and I will ask recipient to sign refusal form and keep him on waiting list for cadaveric KTx. Kidney diseases that could happen due to HBV infection: -Infection with hepatitis B virus (HBV) may be associated with a variety of kidney diseases. -The three most common types of kidney disease resulting from HBV infection are: ●Membranous nephropathy
●Membranoproliferative glomerulonephritis (MPGN) ●Polyarteritis nodosa (PAN) -In addition, HBV infection has been associated with mesangial proliferative glomerulonephritis, immunoglobulin A (IgA) nephropathy, crescentic glomerulonephritis, focal segmental glomerulosclerosis (FSGS), minimal change disease, and amyloidosis, although the causative role of HBV has been debated for some of these conditions. -Rapidly progressive glomerulonephritis (RPGN); In rare patients with RPGN with extensive crescentic disease, presumed to be due to HBV infection. References; -Johnson RJ , Couser WG. Hepatitis B infection and renal disease:Clinical, immunopathogenetic and therapeutic coniderations. Kidney Int 1990;37:663. -Lai KN, Lai FM. Clinical features and the natural course of hepatitis B virus-related glomerulopathy in adults. Kidney Int Suppl 1991;35:S40. -Kupin WL. Viral-Associated GN:Hepatitis B and Other Viral Infections. Clin J Am Soc Nephrol 2017; 12:1529 .
No , I will not accept this donor if the recipient was not desperate as there is ariskof HBV transmission to the recipient , this must be explained clearly to the recipient.
2- Kidney diseases caused by HBV
a- Membranous glomerulopathy.
b-Mesangioproliferative GN with or with out cryoglubulinemia.
c-Polyarteritis nodosa.
d- less common IgA nephropathy.
1. Assume that the potential recipient is not desperate for a kidney from HBsAg positive titre and also HBeAg. Will still go ahead and accept this infected organ? In case the prospective recipient is not willing for such a donor, the transplant should not be proceeded with. But the patient needs to be counselled regarding the status/ risks and benefits of transplantation with respect to such a donor before taking a decision.
Positive HBsAg signifies past HBV infection. Positive HBeAg and HBeAb signify HBeAg positive chronic hepatitis with active viral replication. Such patients have high HBV DNA levels usually with liver damage, and progression to cirrhosis is possible (1).
As per the British Transplantation Society guidelines, kidneys from HBsAg positive donors can be used for any recipient, after risk and benefit assessment (1).
If the donor is positive for HBsAg, HBeAg and HBeAb, I will discuss in detail with the patient regarding this DBD donor, and only if the recipient has urgent need of transplant (poor vascular access, uremia despite adequate hemodialysis, poor tolerability for dialysis), would go ahead with transplant after counselling and consent (2).
The transplant recipient should receive Hepatitis B Immunoglobulin (HBIG) with antivirals (Tenofovir/ entecavir) as prophylactic treatment for HBV, especially non-protective anti-HBsAb titres and if the HBV DNA status of the donor is not known (1-3). If the recipient is HBV immune (Anti HBsAb >10mU/ml), post-transplant antivirals need not be given, but the patient should be monitored closely and antivirals should be given on appearance of HBsAg. Patient should be monitored with liver enzymes, HBsAg and HBV DNA once in 3 months for at least 1 year post-transplant, and subsequently as per the test reports (1,3).
2. Regarding a life donor with HBsAg positive. What are the kidney diseases that could happen due to HBV infection?
The renal disease which can be seen with chronic HBV infection include (4-6):
Srisuwarn P, Sumethkul V. Kidney transplant from donors with hepatitis B: A challenging treatment option. World J Hepatol. 2021 Aug 27;13(8):853-867. doi: 10.4254/wjh.v13.i8.853. PMID: 34552692; PMCID: PMC8422915.
Te H, Doucette K. Viral hepatitis: Guidelines by the American Society of Transplantation Infectious Disease Community of Practice. Clin Transplant. 2019 Sep;33(9):e13514. doi: 10.1111/ctr.13514. Epub 2019 Apr 14. PMID: 30817047.
Kamimura H, Setsu T, Kimura N, Yokoo T, Sakamaki A, Kamimura K, Tsuchiya A, Takamura M, Yamagiwa S, Terai S. Renal Impairment in Chronic Hepatitis B: A Review. Diseases. 2018 Jun 19;6(2):52. doi: 10.3390/diseases6020052. PMID: 29921773; PMCID: PMC6023337.
Shah AS, Amarapurkar DN. Spectrum of hepatitis B and renal involvement. Liver Int. 2018 Jan;38(1):23-32. doi: 10.1111/liv.13498. Epub 2017 Jul 5. PMID: 28627094.
Jaryal A, Kumar V, Sharma V. Renal disease in patients infected with hepatitis B virus. Trop Gastroenterol. 2015 Oct-Dec;36(4):220-8. doi: 10.7869/tg.295. PMID: 27509699.
What are the kidney diseases that could happen due to HBV infection?
1—Membranous nephropathy —
A- secondary membranous nephropathy,
B- Compared with patients who have idiopathic or primary membranous nephropathy, patients with HBV-associated membranous nephropathy are more likely to have microscopic hematuria and lower complement levels
C- The histologic presence of mesangial cell proliferation or mesangial or subendothelial immune deposits, in addition to the typical subepithelial localization, may be a clue to suggest secondary rather than primary membranous nephropathy.
D- low prevalence of anti-PLA2R antibodies and/or PLA2R staining of the immune deposits
2– Membranoproliferative glomerulonephritis (MPGN)
Compared with hepatitis C infection, HBV infection is a rare cause of mixed cryoglobulinemia, which can be associated with MPGN
3– Polyarteritis nodosa (PAN)
HBV-associated PAN typically occurs within four months after the onset of HBV infection.
The presence of HBV-associated disease is suggested by the findings of HBsAg, HBeAg, and HBV DNA (an indicator of viral replication) in the serum
REFERENCES
Kidney disease associated with hepatitis B virus infection (UpToDate)
⭐ I think it is not wise to accept graft from HBsAg postive donor, with higher risk of disease transmission and consequently liver cell failure and higher mortality (once starting immunosupressives therapy).
👉 HBV infection is associated with membranous nephropathy , mesangioproliferative GN, MPGN and cryoglobulinemia.
No i will not accept this donor
Condition associated with hepatitis B is Poly arteries nodsum , cryoglobulinemia and membranous nephropathy and membranoproliferative glomerulonephritis
1- I will not accept this infected organ
2- HBV- related renal disease:
glomerulonephritis, membranous nephropathy, MPGN , Ig A nephropathy, mesangio-proliferative GN
References: 1- Zhang Y, Zhou JH, Yin XL, Wang FY. Treatment of hepatitis B virus-associated glomerulonephritis: a meta-analysis. World journal of gastroenterology: WJG. 2010 Feb 2;16(6):770.
Even with HBsAg positive donor/HBsAg -ve recipients, excellent Ktx can be done.
(Wang XD, Liu JP, Song TR, Huang ZL, Fan Y, Shi YY, Chen LY, Lv YH, Xu ZL, Li XH, Wang L, Lin T. Kidney Transplantation From Hepatitis B Surface Antigen (HBsAg)-Positive Living Donors to HBsAg-Negative Recipients: Clinical Outcomes at a High-Volume Center in China. Clin Infect Dis. 2021 Mar 15;72(6):1016-1023. doi: 10.1093/cid/ciaa178. PMID: 32100025.). So I prefer to go ahead with transplantation after discussing this with potential recipients. Regarding the donor, as he is anti-HeV negative (carrier), I will also check HBV DNA.
No , I will not accept this donor if the recipient was not desperate as there is ariskof HBV transmission to the recipient , this must be explained clearly to the recipient. 1- Kidney diseases caused by HBV a- Membranous glomerulopathy. b-Mesangioproliferative GN with or with out cryoglubulinemia. c-Polyarteritis nodosa. d- less common IgA nephropathy.
Assume that the potential recipient is not desperate for a kidney from HsAg positive titre and also HeAg. Will still go ahead and accept this infected organ?
No ,its high risk of infection ,specially HBV DNA positive and no desperate need or no
HBVS ag positive recipient .
What are the kidney diseases that could happen due to HBV infection?
Better not to transplant if potential recipient is not desperate Diseases due HBV infection include, Membranous nephropathy, Polyarteritis Nodosa -PAN MPGN
1-I will not proceed to transplant the recipient with the patient with hepatitis BsAg positive as the risk of hepatitis, hepatic failure, graft loss, and even death.
2- most common glommularnephritis caused by hepatitis B virus are membranous nephropathy and MPGN
others such as amyloidosis, IgA nephropathy, FSGS MCD
Assume that the potential recipient is not desperate for a kidney from HsAg positive titre and also HBeAg. Will you still go ahead and accept this infected organ?
– no, I would not since there is a high-risk for HBV transmission
Regarding a live donor with HBsAg positive. What are the kidney diseases that could happen due to HBV infection? (1-3)
– Membranous nephropathy
– MPGN (membranoproliferative glomerulonephritis)
– Polyarteritis nodosa (PAN)
– Mesangioproliferative glomerulonephritis
– IgA nephropathy
– Crescentic glomerulonephritis
– FSGS (focal segmental glomerulosclerosis)
– Minimal change disease
– Amyloidosis
Please substantiate your answer.
References
1. Johnson RJ, Couser WG. Hepatitis B infection and renal disease: clinical, immunopathogenetic and therapeutic considerations. Kidney Int. 1990 Feb;37(2):663-76. PubMed PMID: 1968522. Epub 1990/02/01. eng.
2. Lai KN, Lai FM. Clinical features and the natural course of hepatitis B virus-related glomerulopathy in adults. Kidney international Supplement. 1991 Dec;35:S40-5. PubMed PMID: 1770709. Epub 1991/12/01. eng.
3. Kupin WL. Viral-Associated GN: Hepatitis B and Other Viral Infections. Clinical journal of the American Society of Nephrology : CJASN. 2017 Sep 7;12(9):1529-33. PubMed PMID: 27797900. Pubmed Central PMCID: PMC5586580. Epub 2016/11/01. eng.
Assume that the potential recipient is not desperate for a kidney from HsAg positive titre and also HBeAg. Will you still go ahead and accept this infected organ?
– no, I would not since there is a high-risk for HBV transmission
Regarding a live donor with HBsAg positive. What are the kidney diseases that could happen due to HBV infection? (1-3)
– Membranous nephropathy
– MPGN (membranoproliferative glomerulonephritis)
– Polyarteritis nodosa (PAN)
– Mesangioproliferative glomerulonephritis
– IgA nephropathy
– Crescentic glomerulonephritis
– FSGS (focal segmental glomerulosclerosis)
– Minimal change disease
– Amyloidosis
Please substantiate your answer.
References
1. Johnson RJ, Couser WG. Hepatitis B infection and renal disease: clinical, immunopathogenetic and therapeutic considerations. Kidney Int. 1990 Feb;37(2):663-76. PubMed PMID: 1968522. Epub 1990/02/01. eng.
2. Lai KN, Lai FM. Clinical features and the natural course of hepatitis B virus-related glomerulopathy in adults. Kidney international Supplement. 1991 Dec;35:S40-5. PubMed PMID: 1770709. Epub 1991/12/01. eng.
3. Kupin WL. Viral-Associated GN: Hepatitis B and Other Viral Infections. Clinical journal of the American Society of Nephrology : CJASN. 2017 Sep 7;12(9):1529-33. PubMed PMID: 27797900. Pubmed Central PMCID: PMC5586580. Epub 2016/11/01. eng.
Assume that the potential recipient is not desperate for a kidney from HsAg positive titre and also HeAg. Will still go ahead and accept this infected organ?
No ,its high risk of infection ,specially HBV DNA positive and no desperate need or no
HBVS ag positive recipient . What are the kidney diseases that could happen due to HBV infection?
membranous nephropathy ●
Membranoproliferative glomerulonephritis (MPGN) ●
Polyarteritis nodosa (PAN)
Assume that the potential recipient is not desperate for a kidney from HsAg positive titre and also HeAg. Will still go ahead and accept this infected organ?
Only if need demands and potential donor agree to receive this donor kidney after counselling regarding future risk, i wiil go ahead and accept this infected organ. (Actually after individualized assessment of risk and benefit)
Regarding a life donor with HsAg positive. What are the kidney diseases that could happen due to HBV infection?
if the patient is not desperate. There is no emergent situation and can wait for a better donor. Associated HBV infection kidney involvements are: membranaceous nephropathy, MPGN, and polyarteritis nodosa (more common) Less common: mesangioproliferative GN, IgA nephropathy, FSGS, and amyloidosis. Reference: Kidney disease associated with hepatitis B infection in UPtoDate 2023.
Will you accept this donor?
Donor with HBsAg positive, negative HBsAb, HBcAb, HbeAg and HBeAb.
Yes I would accept this donor however the recipient should be informed about the risk of de-novo infection.
Will you accept this donor if LDD and recipient is also HBsAg positive? If yes what conditions should be met?
Yes I would accept this donor.
Additional conditions;
Recipient HBV DNA should be undetectable.
In case of high viral load recipient should be on entecarvir/ tenofovir alafenamide to reduce before transplantation.
HDV DNA and anti-HDV should be done due to risk of HDV super infection.
Assume HBeAg and HBeAb are positive
HBeAg indicates viral replication and presence of HBeAb indicates this is a chronic infection.
No, it would not not change my management.
I would still accept the donor and give lamivudine prophylaxis post-transplant.
What is your differential diagnosis?
HBsAg positive is the serological marker of HBV infection.
Hence this can occur in acute infection and if it persists for more than 6 months will indicate chronic infection.
This donor also has HBeAg is negative could indicate HBeAg negative chronic infection.
This donor with HbsAg positive could also have co-infection with HDV.
How would you manage this case?
DBD with HBsAg positive in both donor and recipient.
HBsAg positive with negative antibodies.
Requires NAAT for HBV and HDV.
Liver aminotransferase levels- ALT and AST should be done to rule out hepatitis.
Imaging of the liver- Abdominal U/S for any features of cirrhosis.
Antivirals- entecarvir/ Tenofovir alafenamide should be given life long due to risk of reactivation due to IS therapy.
References
Diagnosis of hepatitis B Jeong Eun Song, Do Young Kim
Guidelines for Hepatitis B & Solid Organ Transplantation First Edition March 2018
Solid Organ Transplantation From Hepatitis B Virus–Positive Donors: Consensus Guidelines for Recipient Management
Yes, I will accept this donor. However, the recipient should be well informed about the risk of HBV infection.
=========================== Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
Yes, I will also accept him.
Conditions to be met include:
Knowledge of HBV status of the potential recipient. Pre-transplant recipient HBV immunity appears to protect against de novo infection.
Understanding of the appropriate donor-recipient matching. This should be discussed with a viral hepatitis specialist.
Post-transplant anti-HBV prophylaxis to suppress viral activity.
=========================== Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
No, it will not change my management as long as as antivirals are going to be used to suppress HBV after TX. In this setting, no adverse impact on graft or patient survival is expected.
=========================== What is your differential diagnosis? HBe Antigen Negative Chronic Infection (previously “inactive phase”):
Characterized by HBeAg negativity, HBeAb positivity with normal ALT levels & HBV DNA levels being <2000 IU/mL.
Immune escape mutations & HBV viral replication increases, resulting in HBV DNA levels >2000 IU/mL.
Serum ALT levels are raised & can fluctuate significantly. Resultant liver damage can progress rapidly towards cirrhosis & HCC.
=========================== How would you manage this case?
Referral to a specialist in viral hepatitis for full evaluation, including assessment of HBV status, targeted antiviral therapy or prophylaxis, and follow-up.
The current guidelines recommend prophylactic antiviral for HBsAg positive patients when they need IS therapy; however, most of the evidence is based on patients undergoing chemotherapy.
Entecavir is the most commonly used prophylactic antiviral.
Other agents include lamivudine, adefovir, & telbivudine.
HBV DNA load: HBV reactivation is defined as ≥2 log10 increase in HBV DNA levels from baseline, detection of HBV DNA with level >100 IU/ml in a person with undetectable HBV DNA at baseline, or detection of HBV DNA with level ≥100,000 IU/ml in a person with no baseline.
Close monitoring of HBV DNA is required in patients with high titers before KTX.
References
British Transplantation Society Guidelines for Hepatitis B & Solid Organ Transplantation, March 2018
Hyejin Mo, Sangil Min, Ahram Han, In Mok Jung & Jongwon Ha, Outcome after kidney transplantation in hepatitis B surface antigen‑positive patients, Scientifc Reports | (2021) 11:11744 | https://doi.org/10.1038/ s41598-021-91331-y
Donor virology – HBsAg positive, HBsAb negative, HBcAb negative, both HBeAg and HBeAb negative. Both HCV and HIV are negative.
Positive HBsAg indicates current infection and that the person can infect other people. HBsAg is the antigen used to make hepatitis B vaccine.
HBsAb indicates recovery and immunity from hepatitis B viral infection. However, this donor is HBsAb negative.
HBcAb appears at the onset of symptoms in acute hepatitis B infection and persists for life. It indicates previous or ongoing infection with hepatitis B. T his donor is HBcAb negative.
1.DBD donor
Because of the scarcity of donors, I would accept this donor. However, I would inform the recipient about the risk of infection being transferred from the donor. I would allow the recipient to decide whether he/she prefers taking the risk or going back on the transplant waiting list, given that no other donors are available at present.
Recipient needs to be vaccinated. Antiviral prophylaxis is very important in this case and will be given for 6 months post transplant. HBsAg and HBsAb monitoring is crucial, and patient may need second series of vaccination depending on levels of HBsAb being less than 100 units/ml.
British Transplantation Society guidelines recommend using HBsAg positive donor for any recipient in the case of urgent transplant requirement, provided the transplant team does risk assessment and finds appropriate to proceed for transplant. This is the 2018 guideline recommendation.
2.Live donor, recipient HBsAg positive
I would accept this donor, with some amount of risk assessment in the form of the following tests :
liver enzymes monitoring
check for active liver disease, liver biopsy may be indicated
testing for HDV, HCV co infection
HBV DNA, if positive, start antiviral therapy
3.Positive HBeAg, HBeAb and HBsAg
Positive HBsAg along with HBeAg indicates current infection. Positive HBeAb in this setting indicates that the infection has been chronic.
Fulminant HBV infection can occur in naive recipient when they are transplanted with HBsAg positive and HBeAg positive donor grafts. Antiviral medication regimen is crucial in this case. Recipient would have to be vaccinated prior to transplant and given antiviral therapy for 6 months post transplant. Using a different donor may be recommended.
However, if the recipient also has chronic hepatitis, then donor can be accepted with antiviral therapy such as tenofovir with careful monitoring for HBV DNA, HDV and HCV co infection, and liver enzymes.
4.Differential diagnosis
HBV acute
HDV
Chronic active infection HBV
Chronic silent infection if no symptoms
5.Management
HDV RNA and HBV DNA
Vaccination if recipient is naive along with monitoring of HBsAb levels. If below 100 units/ml then second series of vaccination may be needed.
Coordinate with liver specialist.
Monitor liver enzymes
References :
Srisuwarn P, Sumethkul V. Kidney transplant from donors with hepatitis B: A challenging treatment option. World J Hepatol. 2021 Aug 27;13(8):853-867. doi: 10.4254/wjh.v13.i8.853. PMID: 34552692; PMCID: PMC8422915.
Mo, H., Min, S., Han, A. et al. Outcome after kidney transplantation in hepatitis B surface antigen-positive patients. Sci Rep 11, 11744 (2021). https://doi.org/10.1038/s41598-021-91331-y
Will you accept this DBD donor?
–Yes, this donor can be accepted, informed consent about the risk of transmission. If here is no absolute contraindication.
BTS guidelines 2018: If need demands, solid organs of the HBsAg positive organ donor can be used for any recipient, after an individualized assessment of risk and benefit, especially if urgent need for KT (exhausted multiple vascular access, with ongoing uremia despite adequate hemodialysis prescription).
Recipients should be counselled and check their willingness to receive a kidney from donors with HBsAg positivity and discussed the risk of viral transmission to be balanced against continuing on waiting list Management of this condition:
*Evaluate recipient HBV immune status;
– Check for : HBsAg, HBsAB, HBeAg, HBeAb, HBcAb, HBV DNA, HDV
– HBsAg positive donors should not be used for HBV/HDV co-infected or HCV recipients.
– All HBV naive recipients who are must be vaccinated and the response documented.
– If HBsAb are <100 IU/mL, should be vaccinated to decrease reactivation risk ,high dose accelerated vaccine schedule given and second series can be given if no documented response.
– In HBV immune recipients of an anti‐HBc‐positive non‐hepatic organ, no prophylaxis is needed.
– HBIg is not recommended in the prevention of HBV peri‐transplant in non‐hepatic recipients. However, can be used in non-immune recipients along with antiviral therapy.
– Antiviral prophylactic given for 6-12 months after transplantation.
– Monitoring with liver enzymes, HBsAg, and HBV DNA at least every 3 months for at least 12 months post‐transplant
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met? Yes, can proceed with transplantation with the following consideration:no abnormalities of liver function test, no history of liver disease within the previous 28 days, and who are not living in the area of possible mutation strain of HBV
*Additional testing required;
– Including HBeAg, anti‐HBeAb, HBcAb, quantitative HBV DNA
– liver enzymes.
– Check for HDV con-infection. HCV.
– Baseline US surveillance for HCC according to standard guidelines, with or without AFP every 6 months
– Liver biopsy maybe needed to exclude
* if HBV DNA positive should be treated with appropriate antiviral therapy.
* if HDV cannot receive organ from HBsAg positive donor.
*Treatment:
– In HBsAg‐positive KTR, the risk of reactivation of HBV, in the absence of antiviral prophylaxis, ranges from 50% to 94%.
Indicated as untreated HBsAg‐positive dialysis and KTR patients have worse survival rates compared to HBsAg‐negative with rise in HBV DNA, accelerated progression to cirrhosis and occasionally fibrosing cholestatic HBV.
– HBV DNA suppression can significantly improve the survival, ideally to be started pre-transplant.
– Potent NA is recommended; tenofovir or entecavir or lamivudine.
-Tenofovir or entecavir are preferable to lamivudine; due to their potency and high barriers to resistance.
– In those with renal impairment, Entecavir (ETV) or tenofovir alafenamide (TAF) is preferred over tenofovir disoproxil fumarate (TDF).
-Therapy should be continued up to the time of transplant and indefinitely posttransplant as long as the patient remains on IS therapy.
– Peg‐interferon is not recommended in transplant candidates due risk of rejection.
*Monitoring:
– Regular follow‐up and monitoring for response to antiviral therapy HBV DNA, HBVsAg and continue HCC surveillance Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
HBeAg positivity which indicates active viral replication. While anti-HBe positivity indicates the presence of the non-replication phase. The presence of these markers with HBsAg indicates chronic active hepatitis
Donor with chronic active hepatitis:
-Fulminant hepatitis B infection had been reported in a naïve recipient who received kidneys from donors with HBsAg (+)/HBeAg (+) donors due to high infectivity rate.
-This organ can be accepted in urgent need for KT under the cover of antiviral therapy and HBIG.
– Discard the organ if recipient is naïve individual.
Recipient with chronic active hepatitis:
It will be managed the same ensure the following:
– Viral load HBV DNA must be checked.
– Co-infection with HDV. HCV
– Recipient must be referred to hepatologist and specialist in viral hepatitis for full evaluation.
-Must have liver disease staging, liver US
-Antiviral therapy tenofovir or entecavir should be initiated.
– If patient had decompensated liver disease may benefit from combined organ transplantation.
How would you manage this case?
-All candidates must have the following tests:HBsAg,HBeAb, HBeAg, HBeAb and HDV Ab serology, and HBV DNA levels.
– Naïve recipient ideally to be vaccinated pre-transplantation.
– Post-Tx antiviral prophylaxis and monitoring of viral load, liver enzymes and US.
References:
– Mahboobi N, Tabatabaei SV, Blum HE, Alavian SM. Renal grafts from anti-hepatitis B core-positive donors: a quantitative review of the literature. Transpl Infect Dis. 2012 Oct;14(5):445-51. doi: 10.1111/j.1399-3062.2012.00782.x. Epub 2012 Sep 12. PMID: 22970743.
– Guidelines for Hepatitis B & Solid Organ Transplantation British Transplantation Society Guidelines 2018.
– Srisuwarn P, Sumethkul V. Kidney transplant from donors with hepatitis B: A challenging treatment option. World J Hepatol. 2021 Aug 27;13(8):853-867. doi: 10.4254/wjh.v13.i8.853. PMID: 34552692; PMCID: PMC8422915.
– Song JE, Kim DY. Diagnosis of hepatitis B. Ann Transl Med. 2016 Sep;4(18):338. doi: 10.21037/atm.2016.09.11. PMID: 27761442; PMCID: PMC5066055.
Will you accept this DBD donor?
o If need demands, kidney transplantation of the HBsAg positive organ donor can be used for any recipient, after an individualised assessment of risk and benefit
o There is a significant published literature describing the outcome of HBsAg positive kidney donation to HBV immune recipients. In the majority of cases, antiviral prophylaxis has been given after transplantation. Chronic HBV infection appears to be an infrequent outcome, and the need for post-transplant antiviral treatment is not clearly established. If antivirals are not used or if antivirals are stopped after a period of prophylaxis, the recipient should receive long-term monitoring for the appearance of HBsAg
o Kidney transplantation from HBsAg positive donor to a non-immune recipient will result in chronic infection of the recipient. In this setting, antivirals should be given to prevent HBV-related liver damage
o Tuncer and colleagues demonstrated the safety of the use of HBsAg-positive organs in 35 recipients with an anti-HBs titer greater than 10 mIU/mL and negative donor HBV DNA. Recipients with an anti-HBs titer less than 10 mIU/mL were vaccinated to raise their titer to greater than 10 mIU/mL. HBIG and lamivudine were not used in this study. No recipient developed de novo HBV infection or HBV-attributed complications over the 2-year duration of the study
o Transplantation of a HBsAg-positive graft into a HBsAg-negative patient carries a significant risk of de novo infection without adequate prophylaxis. Despite the protection acquired from HBV vaccination or prior exposure to HBV infection, many centers remain reluctant to use HBsAg-positive grafts
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
o All HBsAg positive patients undergoing transplant work up must have the following tests: HBeAg, HBeAb and HDV Ab serology, and HBV DNA levels
o HDV RNA testing must be performed in potential transplant recipients where HDV serology is positive or equivocal
o In patients with positive HBsAg and undetectable HBV DNA, prophylactic therapy is recommended. In patients with HBsAg positivity and HBV DNA less than 2000 IU/mL, preemptive therapy is recommended. In patients with HBV DNA greater than 2000 IU/mL, treatment is recommend. Treatment with an antiviral HBV agent with a high genetic barrier to resistance is preferred ( Tenofovir Entecavir)
o In case of seropositivity, additional serologic markers including anti-HBc (IgM and IgG), HBeAg/ anti-HBeAb, anti-HbsAb, quantitative HBV-DNA PCR and liver biochemistry including transaminases, ALP, GGT and bilirubin to differentiate between active and inactive liver infection
o Active carrier state is defined as HBsAg(+) in the presence of HBeAg(+) or HBeAb, with HBV viral load above 20000 IU/mL with or without elevated alanine aminotransferase (ALT) levels whereas inactive carriers are HBsAg(+) and negative for HBeAg(-) with persistently low viral load, normal liver enzymes and low anti-HBc IgM or anti-HBc IgG levels
o In active HBV carriers, antiviral therapy is indicated until HBeAg becomes negative and viral replication is suppressed. Inactive carriers should be monitored with HBV-PCR and liver enzymes
o The donation of non-liver solid organs from an HBsAg positive donor to an HBsAg positive recipient can be undertaken as long as antivirals are used to suppress HBV after transplantation. In this setting, there appears to be no adverse impact on graft or patient survival
o HBsAg positive and/or HBV DNA positive candidates should be referred to a specialist with expertise in the management of liver disease and HBV infection to determine appropriate antiviral treatment
o CHBV and past HBV are not contraindications for SOT
o Individuals undergoing non-liver SOT who are HBsAg positive must have liver disease staging and suppression of HBV DNA by either tenofovir or entecavir before transplantation if there is a standard clinical indication
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
No, management is the same
What is your differential diagnosis?
1. False positive HBSAg
2. HBV/HDV
3. Early stage of HBV infection
How would you manage this case?
o Discuss with a specialist in viral hepatitis
o Recipient counseling
o Do HDV RNA
o Vaccination according to HBsAb titres
o HBsAg and undetectable HBV DNA, give therapy is recommended
o HBsAg positivity and HBV DNA less than 2000 IU/mL give pre-emptive therapy
o If HBV DNA greater than 2000 IU/mL treatment is recommend
o Treat with an antiviral HBV agent that have a high genetic barrier to resistance (Tenofovir Entecavir)
o Antiviral medications include: Lamuvidine, entecavir, adefovir dipivoxil, tenofovir disoproxil fumarate, telbivudine
References
1. BTS/RA Living Donor Kidney Transplantation Guidelines 2018
2. Guidelines for Hepatitis B & Solid Organ Transplantation. British Transplantation Society Guidelines, 2018.
3. Song JE, Kim DY. Diagnosis of hepatitis B. Ann Transl Med. Sep;4(18):338. doi: 10.21037/atm.2016.11. PMID:27761442;PMCID: PMC5066055.
4. Marinaki S, Kolovou K, Sakellariou S, Boletis JN, Delladetsima IK. Hepatitis B in renal transplant patients. World J Hepatol. 2017 Sep 8;9(25):1054-1063. doi: 10.4254/wjh.v9.i25.1054. PMID: 28951777; PMCID: PMC5596312.
5. Walid S. Ayoub, Paul Martin, Kalyan Ram Bhamidimarri. Hepatitis B Virus Infection and Organ Transplantation
Thanks, Mohamed Excellent answer, but what is the accepted level of HBsAb (immune patient) in order to proceed with transplantation from HBsAg positive donor?
Will explain in more depth what would you do if the DBD donor is HBsAg and HBeAg positive.
In the current index case of potential HBVsAg positive donor and presumed HBVsAg negative recipient: I will not accept the offer since transplanting an HBsAg-positive allograft into an HBsAg-negative recipient carries a significant risk of de novo infection. Even in the presence of preexisting acquired immunity after vaccination or after previous HBV infection should protect the recipient from primary de novo HBV infection, most transplant centres do not transplant kidneys from HBsAg-positive donors, and in most countries these donors can be transplanted only in matched HBsAg-positive recipients.
Will you accept this donor as a live donor if the recipient is also HBsAg positive?
The donor has HBVsAg positive to recipient with HBVsAg positive, The answer is yes, I can accept the offer provided that:
-With use of long life prophylactic anti-viral therapy entecavir which can confer long-term survival benefits.
-Or successfully immunized recipients (HBs Ab > 10 IU/ml and no need for prophylaxis.
Individuals undergoing non-liver solid organ transplantation who are HBsAg positive must have liver disease staging and suppression of HBV DNA by either tenofovir or entecavir before transplantation (BTS).
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
Evidence of chronic HBV, if confirmed on two samples six months apart. We can proceed for transplantation with prophylaxis anti viral to prevent replication with close monitoring.
What is your differential diagnosis?
HBVsAg in the deceased donor can be active HBV infection or if it more than 6 months denoting chronic infection.
How would you manage this case?
-The appropriate matching of recipient with a donor positive for HBsAg should be discussed with a specialist in viral hepatitis.
-All potential recipients should be counselled during the assessment process about the possibility of receiving a kidney from a donor with past or current HBV infection.
-Commence anti-viral prophylaxis for recipient mostly long life to prevent viral replication with close monitoring with virology markers ,ALT and DNA.
Thanks, Mohamed I disagree with the first part of the answer. I would accept HsAg positive deceased donor into an immune recipient (adequate HBsAb preferable >100 unit/ml) or into HBsAg positive recipient. Surprisingly, you came nicely regarding the rest of the scenario in spite being difficult
If need demands, the non-liver solid organs of the HBsAg positive organ donor can be used for any recipient, after an individualised assessment of risk and benefit(1).
Will you accept this donor as a live donor if the recipient is also HBsAg positive?
I will proceed in the transplant process provided that both the recipient and donor are positive for HBsAg and no evidence of HDV infection. Based on BTS guidelines as it is recommended that the kidneys, heart and lungs from the HBcAb positive organ donor can be used for any recipient, and the risk of de novo HBV infection is low. HBsAg positive donors should not be used for HBV/HDV co-infected recipients(1).
If yes, what are the conditions that should be met?
The following conditions have to be met(2):
a) Liver disease staging and suppression of HBV DNA: Individuals undergoing non-liver solid organ transplantation who are HBsAg positive must have liver disease staging and suppression of HBV DNA by either tenofovir or entecavir before transplantation if there is a standard clinical indication(1).
b) Individualised assessment of risk and benefit: If need demands, the non-liver solid organs of the HBsAg positive organ donor can be used for any recipient, after an individualised assessment of risk and benefit.
c) Antiviral prophylaxis(lamivudine prophylaxis): lamivudine prophylaxis may be given for six months after transplantation, although the risk of transmission is very low.
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
HBeAgpositivity reflects the ongoing viral replication. This test is mostly replaced by the quantitative viral load(HBV DNA). Positive HBeAg or detectable viral load put the recipient at high risk of having post-transplant HBV infection. So, waiting for HBV DNA level to be undetectable is advisable. If need demands, antiviral medications and HBIG can be used while proceeding in the transplant process(2).
What is your differential diagnosis?
a) Acute HBV infection.
b) HBeAg-negative chronic HBV infection.
How would you manage this case?
1. To screen for co-infection with HDV.
2. The patient is immunocompromised, so antiviral medications (entecavir or tenofovir) should be started. Antiviral treatment is indicated in certain subgroups of patients with acute HBV infection:
a) Fulminant hepatitis B
b) Severe AHB – based on the presence of at least two of the following criteria:
· bilirubin >100 μmol/L
· international normalised ratio (INR) ≥1.6
· hepatic encephalopathy
c) Protracted disease course – persistent symptoms or marked jaundice for more than four weeks after presentation
d) Immunocompromised host
Therapy should be continued for at least three months after seroconversion to HBsAb or 12 months after anti-HBe seroconversion without HBsAg loss(1).
References
1. Guidelines for Hepatitis E & Solid Organ Transplantation; first edition (BTS guidelines)
2. Srisuwarn P, Sumethkul V. Kidney transplant from donors with hepatitis B: A challenging treatment option. World J Hepatol. 2021 Aug 27;13(8):853-867. doi: 10.4254/wjh.v13.i8.853. PMID: 34552692; PMCID: PMC8422915.
Thanks, Safi for your excellent answer Regarding a living donor with HsAg positive. What are the kidney diseases that could happen due to HBV infection?
Will you give the kidney with high HBV DNA to any recipient with a cover of antiviral treatment? Support your answers by evidence, please.
Will you accept this DBD donor?
Yes, but before that need to know the recipient status
If recipient is HBsag +ve and don’t have active infection and there is no co infection with HDV- can proceed for transplant
If recipient is HbsAg -ve the donation can be accepted in special circumstances judging the risk against benefit like viral transmission, vascular access problem, long waiting time for transplantation, age of patients, comorbidities, degree of sensitization, vaccination status, most important is inform consent of HBV infection and need of antiviral medication
Antiviral for prevention of infection and reactivation to be given for life long and in case of vaccinated individual for one year. Pre transplant booster vaccination.
With monitoring of HBsAg and HBcAb 3 monthly for 1 year then and HBV DNA (NAT) 6 monthly
Moreover, meanwhile the transplantation is ongoing we need to recheck the HbsAg if it false positive or need to do viral DNA PCR from store donor sample
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
Yes, first of all the donor and recipient should have HBV DNA PCR for virus load, if it is positive and high, better to treat the donor and recipient with antiviral before the transplantation.
Both should not have active HBV infection, coinfection with HDV and liver enzyme are in normal limits.
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
Yes
The recipient should be treated with HBV immunoglobulin if anti Hbs is less than 100 IU
What is your differential diagnosis?
1.Early HBV infection
2.Results can be falsely positive for HBsAg
3.Recent vaccinated donor with false positive result
How would you manage this case?
MDT meeting with hepatologist or microbiologist or infectious disease specialist
Counseling the recipient and take inform consent for the possibility of HBV infection
A pre-transplant vaccine booster should be administered
Antiviral for prevention of infection and reactivation to be given for life long and in case of vaccinated individual for one year. Pre transplant booster vaccination.
Start entecavir or tenofovir alafenamide at transplant for DCD or before in living donation if HBV load is high
Close monitoring of HbsAg, Anti HBc 3 monthly then HBV DNA (NAT) 6 monthly along with LFT monitoring post-transplantation.
HBVv immunoglobulin to be administer if recipient immune status is not known or vaccinated with anti HBs <100 IU
References:
1.Lecture : Prof May A Hassbola: kidney transplant in patient with HBV
2.Veroux, M., Ardita, V., Corona, D., Giaquinta, A., Ekser, B., Sinagra, N., … & Veroux, P. (2016). Kidney transplantation from donors with hepatitis B. Medical Science Monitor: International Medical Journal of Experimental and Clinical Research, 22, 1427.
Membranous glomerulopathy Membranoproliferative GN Iga Nephropathy Polyarthritis nodosa Acute hepatitis- pigment nephropathy Chronic hepatitis- cirrhosis- HRS
Acute hepatitis – Herbal medication for Jaundice in our region- AIN
so, we need to counsel the donor as well for the risk of these disease due to hepatitis B virus.
Will you accept this DBD donor? Yes. Recipients with HBV immunity from vaccination may receive kidney transplant from donors with chronic infection. However, prophylaxis with antiviral agents and hepatitis B immunoglobulin is necessary. Recipients without prior infection or immunity should generally avoid transplant from donors with positive HBsAg except in extreme and urgent circumstances such as vascular access exhaustion. Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met? Yes, and the conditions will include:
1. Rule out an active infection in both the donor and recipient using the HBV DNA. If DNA level is high, it’s better to treat to undetectable viral loads before transplantation except in extreme circumstances.
2. A donor or recipient with active infection should also be screened for other viruses such as HIV, HCV, HEV. Do liver scan, LFT to also assess for cirrhosis. Presence of decompensated cirrhosis might require simultaneous liver and kidney transplantation.
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management? No, it won’t. Though, this signifies active replication, HBV does not replicate in the kidneys, so if the recipient is immune from vaccination or previous infection transplant can still go ahead. However, in a recipient without prior infection or vaccination, transplant should occur in extreme cases only.
What is your differential diagnosis?
Acute hepatitis
Exacerbation of chronic HBV infection
Reactivation of chronic hepatitis B
Superinfection of hepatitis B carrier with acute hepatitis A, C, D or E
Acute hepatitis from other drugs or toxins on background of hepatitis B carrier
How would you manage this case? Recipients with HBV immunity from vaccination may receive kidney transplant from donors with chronic infection. However, prophylaxis with antiviral agents using either entecavir or tenofovir alafenamide and hepatitis B immunoglobulin is necessary. Recipients without prior infection or immunity should generally avoid transplant from donors with positive HBsAg except in extreme and urgent circumstances such as vascular access exhaustion. They should also receive prophylaxis.
Reference
Kidney transplantation in adults: Hepatitis B virus. Up-to-Date [database on the internet]. Waltham(MA):UpToDate;2022[cited 7 March 2023]. Available from: http://www.uptodate.com
Anna SF Lok. Hepatitis B virus: Screening and diagnosis. Up-to-Date [database on the internet]. Waltham(MA):UpToDate;2022[cited 7 March 2023]. Available from: http://www.uptodate.com
You were offered kidneys from a 53-year-old male DBD (donor after brain stem death) donor who suffered from SAH (grade 5) complicating cerebral aneurysm. His retrieval S Cr was 78 µmol/L. Virology was reported as follows: HBsAg positive, HBsAb negative, HBcAb negative, both HBeAg and HBeAb are negative. Both HCV and HIV are negative. Will you accept this DBD donor? Yes; I will accept this donors kidneys, and well consider them to HBs Ag +ve recipient whom HDV co-infection is excluded. Otherwise can be given to HBsAg +ve recipient is special conditions- not tolerating dialysis, persistent uremia, or long time on list with prolonged dialysis time, or no dialysis access available, with recipient counselling and consent signed. I shall review the medical file of the patient for ALT level, HBV DNA, to clarify his disease burden. It is acceptable to have such donors in the presence of anti-viral therapy (tenofovir and entecavir) that suppress HBV replications, with no effect on graft and patient survival. And the recipient should undergo frequent monitoring for appearance of HBs Ag. Using HBsAg positive kidneys in patients with HBsAb immunity, showing good graft and patient survival using a combination of HBIG and lamivudine prophylaxis. Life-long combination therapy with HBIG and a potent NA can be given to high risk patients for HBV recurrence:
(1) HBV DNA positive at time of transplant.
(2) HBeAg positive patients.
(3) Those transplanted for hepatocellular carcinoma.
(4) HIV co-infected.
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met? Yes, I will accept his kidneys for HBs Ag +ve recipients. But I would start him on treatment for HBV to the donor, and ask for ALT, and HBV DNA. Considering high risk for HBV reactivation, so anti- viral medications should be started immediately, and continued indefinitely, with frequent monitoring of HBV DNA and ALT at least every 3 months in the first year and 6 monthly thereafter.
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management? I would ask for ALT level and HBV DNA level, and will start antiviral therapy in living donor to improve liver function and decrease reactivation after transplantation, in deceased donors I will explain the risk to the potential recipient, with a signed concent, and early start of antiviral medications In this situation and by definition the donor then considered to have chronic active hepatitis B. renders the recipient at higher risk of fulminant hepatic failure/cirrhosis and HCC. In this scenario expert opinion is a must, with multidisciplinary team discussion, and dicission.
References: (1) European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu; European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017 Aug;67(2):370-398. doi: 10.1016/j.jhep.2017.03.021. Epub 2017 Apr 18. PMID: 28427875. (2) Huprikar S, Danziger-Isakov L, Ahn J, Naugler S, Blumberg E, Avery RK, Koval C, Lease ED, Pillai A, Doucette KE, Levitsky J, Morris MI, Lu K, McDermott JK, Mone T, Orlowski JP, Dadhania DM, Abbott K, Horslen S, Laskin BL, Mougdil A, Venkat VL, Korenblat K, Kumar V, Grossi P, Bloom RD, Brown K, Kotton CN, Kumar D. Solid organ transplantation from hepatitis B virus-positive donors: consensus guidelines for recipient management. Am J Transplant. 2015 May;15(5):1162-72. doi: 10.1111/ajt.13187. Epub 2015 Feb 23. PMID: 25707744. (3) Guidelines for. Hepatitis B & Solid Organ. Transplantation. British Transplantation Society Guidelines
The index patient is being offered a DBD (donor after brain death) donor with good terminal renal function. The donor is HBsAg positive. Other serological tests (HBsAb, HBcAb, HBeAg, HBeAb, HIV and HCV) are negative.
Positive HBsAg signifies past HBV infection.
As per the British Transplantation Society guidelines, kidneys from HBsAg positive donors can be used for any recipient, after risk and benefit assessment (1).
Hence, I will accept this DBD donor, especially if the recipient has urgent need of transplant (poor vascular access, uremia despite adequate hemodialysis, poor tolerability for dialysis) (2).
Such a donor should not be used if the recipient is HBV/HDV co-infected (1).
Transplant recipient should receive Hepatitis B Immunoglobulin (HBIG) with antivirals (Tenofovir/ entecavir) as prophylactic treatment for HBV, especially non-protective anti-HBsAb titres and if the HBV DNA status of the donor is not known (1-3).
If the recipient is HBV immune, post-transplant antivirals need not be given, but the patient should be monitored closely and antivirals should be given on appearance of HBsAg.
Patient should be monitored with liver enzymes, HBsAg and HBV DNA once in 3 months for at least 1 year post-transplant, and subsequently as per the test reports (1,3).
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
Yes. A HBsAg positive live donor can be accepted for HBsAg positive recipient as long as antivirals are used to manage HBV replication post-transplant (1).
There is high risk of reactivation of HBV, hence HBsAg positive patients who did not require antivirals pre-transplant should be started on antivirals (tenofovir or entecavir) at time of transplant and continued indefinitely, irrespective of HBV DNA levels (3).
Patient should be monitored with liver enzymes and HBV DNA once in 3-6 months and ultrasound abdomen once in 6 months (2,3).
In nutshell, this clinical scenario requires:
1) Recipient should be counselled regarding the clinical scenario.
2) Hepatologist should be involved in management.
3) Post-transplant antiviral prophylaxis would be required.
4) Regular post-transplant monitoring of LFT and HBV DNA should be done as per protocol.
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management? What is the differential diagnosis? How would you manage this case?
Positive HBeAg and HBeAb signify HBeAg positive chronic hepatitis with active viral replication. Such patients have high HBV DNA levels usually with liver damage, and progression to cirrhosis is possible (1).
If the donor is positive for HBsAg, HBeAg and HBeAb, I will accept this DBD donor, y if the recipient has urgent need of transplant (poor vascular access, uremia despite adequate hemodialysis, poor tolerability for dialysis) (2). The treatment protocol will remain same. The transplant recipient should receive Hepatitis B Immunoglobulin (HBIG) with antivirals (Tenofovir/ entecavir) as prophylactic treatment for HBV, especially non-protective anti-HBsAb titres and if the HBV DNA status of the donor is not known (1-3). If the recipient is HBV immune, post-transplant antivirals need not be given, but the patient should be monitored closely and antivirals should be given on appearance of HBsAg. Patient should be monitored with liver enzymes, HBsAg and HBV DNA once in 3 months for at least 1 year post-transplant, and subsequently as per the test reports (1,3).
If the recipient is positive for HBsAg, HBeAg and HBeAb, then a detailed hepatic evaluation is required prior to proceeding with kidney transplant. In such a patient, there may be a possibility of HBV-related liver disease, requiring a combined liver-kidney transplant (1).
Srisuwarn P, Sumethkul V. Kidney transplant from donors with hepatitis B: A challenging treatment option. World J Hepatol. 2021 Aug 27;13(8):853-867. doi: 10.4254/wjh.v13.i8.853. PMID: 34552692; PMCID: PMC8422915.
Te H, Doucette K. Viral hepatitis: Guidelines by the American Society of Transplantation Infectious Disease Community of Practice. Clin Transplant. 2019 Sep;33(9):e13514. doi: 10.1111/ctr.13514. Epub 2019 Apr 14. PMID: 30817047.
Excellent Amit Assume that the potential recipient is not desperate for a kidney from HsAg positive titre and also HeAg. Will still go ahead and accept this infected organ? Please substantiate your answer.
Positive HBeAg and HBeAb signify HBeAg positive chronic hepatitis with active viral replication. Such patients have high HBV DNA levels usually with liver damage, and progression to cirrhosis is possible (1).
If the donor is positive for HBsAg and HBeAg, I will accept this DBD donor, only if the recipient has urgent need of transplant (poor vascular access, uremia despite adequate hemodialysis, poor tolerability for dialysis) after detailed patient counselling (2). If the recipient does not agree for such a patient, then the transplant will not be done.
Srisuwarn P, Sumethkul V. Kidney transplant from donors with hepatitis B: A challenging treatment option. World J Hepatol. 2021 Aug 27;13(8):853-867. doi: 10.4254/wjh.v13.i8.853. PMID: 34552692; PMCID: PMC8422915.
Hepatitis B surface antigen (HBsAg) is the serologic hallmark of HBV infection. It can be detected using an enzyme immunoassay (EIA).
HBsAg appears in serum 1 to 10 weeks after an acute exposure to HBV
In patients who subsequently recover, HBsAg usually becomes undetectable after four to six months.
Persistence of HBsAg for more than six months implies chronic infection.
The disappearance of HBsAg is followed by the appearance of hepatitis B surface antibody (anti-HBs). In most patients, anti-HBs persists for life, thereby conferring long-term immunity from reinfection. However, over time, anti-HBs may disappear in some patients, and they may have only isolated hepatitis B core antigen (anti-HBc) IgG.
2-Will you accept this donor as a live donor if the recipient is also HBsAg positive?
YES
3-If yes, what are the conditions that should be met?
May administer hepatitis B immune globulin in addition to antiviral therapy to prevent de novo infection.
Recipients should be vaccinated if they have no prior immunity, although the efficacy in eliciting an anti-HBs response is reduced due to the effect of immunosuppressive medications.
The optimal duration of antiviral therapy is unknown; we administer therapy for 1 year.
4-Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
NO
Hepatitis B e antigen and antibody — Hepatitis B e antigen (HBeAg) is a secretory protein that is processed from the precore protein. It is an early antigen and not an envelope antigen. It is generally considered to be a marker of HBV replication and infectivity. The presence of HBeAg is usually associated with high levels of HBV DNA in serum and higher rates of transmission of HBV infection from carrier mothers to their babies and from patients to health care workers
HBeAg to anti-HBe seroconversion occurs early in patients with acute infection, prior to HBsAg to anti-HBs seroconversion However, HBeAg seroconversion may be delayed for years to decades in patients with chronic HBV infection. In such patients, the presence of HBeAg is usually associated with the detection of high levels of HBV DNA in serum and active liver disease.
5-What is your differential diagnosis? Susceptible Prior infection (inactive)
Immune due to hepatitis B vaccination
Acutely infected Chronically infected
6-How would you manage this case?
HBV DNA assays use real-time PCR techniques
The diagnosis of chronic HBV infection is based upon the persistence of HBsAg for more than six months . Additional tests for HBV replication, HBeAg and serum HBV DNA and ALT, should be performed to determine if the patient should be considered for antiviral therapy.
All patients with chronic HBV infection should be regularly monitored because HBV DNA and alanine transaminase (ALT) levels vary during the course of infection to monitor for progression of liver disease
HBeAg-negative patients who have normal serum ALT and low (<2000 international units/mL) or undetectable HBV DNA are considered to be in an inactive carrier state. These patients generally have a good prognosis and antiviral treatment
Choice of regimen
For most kidney transplant recipients who require antiviral therapy to prevent de novo HBV infection, preferred antiviral regimens include entecavir and tenofovir. Antiviral therapy should be started at the time of transplantation.
administer treatment for one year
administer entecavir since it is not associated with kidney toxicity; dose adjustments are required for those with reduced kidney function
Entecavir and tenofovir are preferred over lamivudine, which had previously been the mainstay of treatment, because lamivudine has been associated with a high rate of drug resistance with long-term use
Pegylated interferon alfa should not be used in kidney transplant recipients, because it may precipitate acute allograft rejection
. Adefovir should also be avoided due to its nephrotoxicity and its weak antiviral activity
Thank you. Your systematic approach is highly regarded. I wonder about your comment that you will not change management plans in case donor is HbeAg+ve! You discussed this point in details assuming this patient would indicate high viral replication and would be highly infectious, Do you still accept this patient as a donor?
PATIENT IS HIGH RISK DONOR
YES ,I WILL ACCEPT AS DONOR IF THERE IS OTHER OPTION
IF THERE IS CHANCE FOR TREATMENT DONOR BEFORE TRANSPLANT WILL BE BETTER
Considerations for donor selection — In general, kidney transplant recipients with prior (ie, hepatitis B surface antigen [HbsAg] negative, hepatitis B core antibody [anti-HBc] positive) or chronic (HBsAg positive) hepatitis B virus (HBV) infection may receive a kidney transplant from any donor regardless of the HBV status of the donor
Donors — Potential kidney donors (living and deceased) should be tested for HBsAg, anti-HBc, and HBV DNA nucleic acid testing (NAT); this approach is consistent with guidelines from the United States Centers for Disease Control and Prevention
For living donors, testing should be done within the 28 days before organ procurement
for deceased donors, testing should be performed within 96 hours before organ procurement. Frequently in deceased donors, only qualitative HBV DNA testing is performed since quantitative testing might delay donor decision-making.
In countries where there are barriers to access to the HBV DNA assay, testing for HBV DNA can be reserved for donors who are positive for HBsAg or anti-HBc.
It should be noted that HBV does not reside or replicate in the kidney, so the risk of HBV transmission is via residual blood and peripheral blood mononuclear cells in these organs despite flushing
Suitable donors — The suitability of a donor-recipient pair for kidney transplantation depends upon the HBV status of both the donor and recipient
Recipients with HBV immunity due to vaccination and recipients without evidence of prior infection or immunity should ideally receive a kidney transplant from the following donors: ●Living or deceased donors who have no evidence of prior HBV infection with or without immunity to HBV through vaccination (HBsAg negative, anti-HBc negative, anti-HBs positive). ●Living or deceased donors with prior HBV infection (HBsAg negative, anti-HBc positive). The risk of HBV transmission is negligible unless the donor is HBV DNA positive, in which case prophylactic antiviral therapy is recommended
– Will you accept this DBD donor?
Yes ,Recent guidelines recommended that kidneys from HBsAg (+) donors can be transplanted to recipients with assessment of the risk and benefit along with an informed consent.
When allocated to serology-matched recipients, can have an excellent short-term outcome ,but for long term outcomes need to be furtherly evaluated -Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
Yes, Treatment of HBsAg-positive renal transplant recipients with antiviral treatment confers long-term survival benefit, and tenofovir or entecavir is effective in cases with resistance to lamivudine.
Antiviral therapy with lamivudine is effective in suppressing HBV DNA and decreasing elevated liver enzymes , and can improve graft survival almost comparable to HBsAg-negative recipients
In spite that antiviral treatment need to be continued for life post renal transplant due to the risk of HBV reactivation and worsening of disease course , another study demonstrated a successful withdrawal of antiviral treatment in 4 HbsAg-positive renal transplant recipients with complete suppression of HBV infection after being on antiviral therapy for 14.3 months, the cases maintained HBV-DNA negative for a median of 60.5 months .
Studies evaluating the transplantation of HBsAg-positive kidney donors to HBsAg-positive recipients with natural immunity is rational and mostly safe. -Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
If the donor has HBe Ag ,HBe Ab and HBsAg positive ,indicating active hepatitis with viral replication and likely to progress to chronic hepatitis ,HBV DNA level need to be tested
The donor has to be treated before donation to have a sustained viral response .
The recipient and the donor have to be counselled .
The transplantation can be done if the donor is cured and the antibody titer of the recipient, just before transplantation, is at least 10 IU/ml and with concomitant administration of one dose of booster vaccination in combination with hepatitis B hyperimmune globulin(HBIG) .
Antiviral prophylaxis postoperatively need to be started . The need and the duration of antiviral treatment in this patient population have not been investigated; moreover, data about monitoring long term are lacking. It seems logical to assume that antibody titer should be checked and booster vaccination should be administered when the titer falls below 10 IU/ml, since transplant recipients receiving immunosuppression are at risk for viral reactivationif it has been transmitted from the donor.
HBeAg‐positive patients should be treated until HBV DNA and HBeAg are cleared and anti‐HBe seroconversion occurs. Additional treatment is needed for at least 6–12 months after anti‐HBe seroconversion to prevent virological reactivation.
-What is your differential diagnosis?
HB s Ag indicates infection risk
Chronic hepatitis B virus infection
Acute Hepatitis B virus infection
Incubation period of HBV infection
Coinfection of HBV and HDV -How would you manage this case?
The recipient need to be counselled and hepatologist need to be involved
The recipient ‘s virological status need to be assessed beside the routine assessment tests by checking HBsAg ,HBcAb ,HB s Ab ,HB e Ag ,HBe Ab and HBV DNA level.
If the anti-HBs is > 100 mIU/mL, transplantation can proceed without antiviral prophylaxis. However, if HBV DNA was not measured by a method of optimum low detection limit or the result of HBV DNA cannot be obtained , antiviral as tenofovir or entecavir can be prescribed to decrease HBV transmission risk .
In the setting of HBsAg (+)/HBV DNA (+) donor, antiviral prophylaxis with or without HBIG will be needed among patients with different levels of anti-HBs concentration
Antiviral treatment along with HBVIg can be given HBIG provides passive immunity for a high concentration of anti-HBs that are aimed to act as neutralizing antibodies to HBV
Naïve recipients or previously immune recipients who have anti-HBs concentration less than 10 mIU/mL while the KDIGO guideline suggested Anti-HBs Ab concentration <100 mIU/mL can decrease rapidly to a non-protective level and may require a booster dose .
HBs Ab monitoring at least yearly is needed . A further booster dose of vaccine may be required, by either a single-shot high dose (40 µg) or a total complete course with a follow-up level at 4-wk after a complete course of treatment. Reference
-Srisuwarn P, Sumethkul V. Kidney transplant from donors with hepatitis B: A challenging treatment option. World J Hepatol. 2021;13(8):853-867.
– Veroux M, Ardita V, Corona D, et al. Kidney Transplantation From Donors with Hepatitis B. Med Sci Monit. 2016;22:1427-1434. Published 2016 Apr 28.
– Marinaki S, Drouzas K, Skalioti C, Boletis JN. Hepatitis B and C in Kidney Transplantation. Advances in Treatment of Hepatitis C and B [Internet]. 2017 Mar 8.
Kidney & thoracic organ transplantation have lower risk of HBV transmission.
Donor with HBV infection included in extended donor criteria organs.
All organ from donor with HBsAb+ve (HBsAg+ve or -ve) can be used for transplantation.
Using of HBsAg +ve kidney donors to an immune recipient(HBsAb>10mU/ml) associated with low risk of transmission.
This donor HBeAg & HBeAb negative mean low replication & infectivity.
Yes, I accept this patient, but immune status of the recipient should be known. If recipient HBsAb>10mU/ml he may not need prophylaxis, but if he is not immune prophylaxis with lamuvidin needed.
Live donor with HbsAg+ve:
Live donor with positive HBsAg should undergo HBV DNA measurement, if undetected the donor can accepted.
Yes, I can accept this donor if the recipient :
protected recipient (HBsAb+ve).
no abnormalities of liver function.
no history of liver disease within 28 days.
not live in area of possible mutant strain of HBV.
HBeAg & HBeAb positive in addition to HBsAg+ve:
It mean active viral replication.
HBV DNA measurement is mandatory
need NA with or without HBIg according recipient immune status.
Close monitoring of LFT & viral load(post transplantation).
References:
BTS Guidelines for Hepatitis B & Solid Organ Transplantation, 2018.
Srisuwarn P. and Sumethkul V. Kidney transplant from donors with hepatitis B: A challenging treatment option. World J Hepatic, 2021;13(8):853-867.
Yes . Although transplanting HBsAg negative kidney recipients from HBsAg positive deceased donors carries significant risk of denovo infection , total exclusion of HBsAg donors from the donor pool would significantly reduce the supply of kidney allografts especially in endemic areas . Immunization status of the recipient either due to vaccination or previous infection and proper prophylaxis post kidney transplant will play an important protective role .
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
yes .
It is reasonable to transplant HbsAg-positive kidneys into HbsAg positive recipients .
This patient needs proper evaluation and further testing including HBeAg, anti -HBe, quantitative HBV DNA, liver enzymes, and a baseline abdominal ultrasound with proper antiviral treatment (tenofovir,entecavir) as clinically indicated .
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
Presence of HBeAg and HBeAb indicates replicating virus which carries high risk of post transplant complications of HBV infection , the patient should be counselled about the risk and should check his immune status in addition start of proper antiviral treatment especially if he was waiting for along period before having a kidney donor .
What is your differential diagnosis
–Acute or chronic HBV infection -Combined HBV and HDV infection
How would you manage this case?
Management is MDT including (hepatologist,nephrologist,and clinical pharmacist )Proper evaluation of the patient liver function , serology , immunization status plus PCR and imagining .
Counsel the patient about the risk after transplant, and take the consent .
Start of antiviral prophylaxis treatment as clinically indicated
Follow up liver function and serology every 3 months in the first year and then every 6 months .
He should also undergo surveillance for HCC, according to published guidelines in the non -transplant population, with an abdominal ultrasound with or without alpha -fetoprotein every 6 months.
Reference :
Transplantation. 2012 Aug 15;94(3):205-10. doi: 10.1097/TP.0b013e31824e3db4
Yes MDT approach is good. One many have to decide at 3 am that MDT would not be possible at that time. However, I shall take opinion of other colleagues and experts to help in decision-making.
Donor stauts HBsAg positive
HBsAb negative
HBcAb negative
HBeAg and HBeAb are negative.
HCV and HIV are negative. Will accept as donor if the following criteria are met.
Better to arrange further testing of donor with HBs Ab and HBV DNA level with immune status of recipient before transplantation .
Recipient vaccination status and recipient serology of HBV.
If the recipient is also positive for HBsAg than one can proceed also with the prophylaxis treatments
It is widely acknowledged that there is a sizable risk of novo infection when an HBsAg-positive allograft is transplanted into a recipient who is HBsAg-negative.
The recipient should be protected from primary de novo HBV infection by preexisting acquired immunity from vaccination or prior HBV infection, but most transplant centers do not transplant kidneys from HBsAg-positive donors, and in most nations these donors can only be transplanted into matched HBsAg-positive recipients.
Lamivudine antiviral medication is efficient in reducing transaminase levels and lowering HBV DNA. It is also linked to increased graft survival that is almost on par with HBsAg-negative patients.
Live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
Yes we can proceed for transplantation in very high risk condition as risk of De novo disease is very high. Conditions in which this donor is accepted are;
Recipient has a long waiting period.
Age
Other co morbidities
Dialysis risk and vascular access problem HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
This patient have acute infection and seroconversion and he need treatemt befor proceding to transplantation
The recipient needs to be warned about the elevated risk of infection and other problems and start taking Entecavir or tenofovir as soon as possible after the transplant. Differentials are
HBV
HVE
HBV with co-infection Management;
Counselling
Multidisciplinary team approach
Antiviral treatment References;
Huprikar S, Danziger-Isakov L, Ahn J, et al. Solid organ transplantation from hepatitis B virus-positive donors: Consensus guidelines for recipient management. Am J Transplant. 2015;15:1162–72
Fabrizi F, Dulai G, Dixit V, et al. Lamivudine for the treatment of hepatitis B virus-related liver disease after renal transplantation: meta-analysis of clinical trials. Transplantation. 2004;77:859–64.
42. Yap DY, Tang CS, Yung S, et al. Long-term outcome of renal transplant recipients with chronic hepatitis B infection- impact of antiviral treatments. Transplantation. 2010;90:325–30.
British Transplantation Society Guidelines: Guidelines for Hepatitis B & Solid Organ Transplantation 2018.
Yes MDT approach is good. One many have to decide at 3 am that MDT would not be possible at that time. However, I shall take opinion of other colleagues and experts to help in decision-making.
Will you accept this DBD donor? Yes, But if the need demands
Assess the risk/benefit.
Counsel the recipient about the risk of getting HBV infection.
Combination therapy of HBIg and a potent NA to prevent a recurrence.
Vaccination guided by HBsAb titer.
If the donor is considered for liver Tx and the recipient is HBsAg+ve
Ideally, the recipient should receive either tenofovir or entecavir till HBV DNA is undetectable level, but in urgent demand, treatment can be started with transplantation.
We can donate as both donor and recipient are HBsAg+ve but after the exclusion of HDV infection.
The use of HBIg is not recommended.
If HBeAg +ve, HBeAb +ve
Considered as high risk.
Chronic active hepatitis phase.
Assess liver enzymes.
Test for HBV DNA level.
Should receive HBIg and a potent NA to prevent a recurrence.
Differential diagnosis This patient had an active chronic hepatitis B infection. Reference BTS guideline, Hepatitis B and SOT 2018
DBD donor:
HBsAg positive, HBsAb negative, HBcAb negative, both HBeAg and HBeAb are negative. Both HCV and HIV are negative. Will you accept this DBD donor? Yes, I will.
Simply, the non-liver solid organs of the HBsAg positive organ donor can be used for any recipient, after an individualized assessment of risk and benefit. Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
Yes, I will.
We should request HBV DNA for the donor and herein, we have three possibilities for our recipients.
1-HBsAg positive recipient: Many studies shown safety of transplantation without elevation of transaminases but we consider antiviral treatment with Entecavir and clinical follow up with HBV DNA and liver function testes.
2-HBsAb positive with titer <10 IU/L: Consider vaccination, prophylaxis with high dose Immunoglobulin or Lamivudine and strict follow up by HBV PCR and liver function test.
3-HBcAb or HBsAb >10 IU/L: No need for prophylaxis and just clinical follow up with HBV DNA and liver functions. Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
Active infection with viral replication, No, the management remained the same regardless the DBD donor HBeAg/Ab status i.e., I will accept the DBD donor, the recipient must counseled about high risk of infection and complications that might be occurred and get Entecavir or tenofovir right away from the time of transplantation. What is your differential diagnosis?
–False positive HBsAg results.
– Early stage of HBV infection.
–HBV and HDV co-infection. How would you manage this case? –Refer to hepatology consultant.
-Counseling the recipient about the possibility of HBsAg-positive organs
-Pre-transplant vaccine booster dose according to HBsAb titer.
-Start with Entecavir directly according to GFR.
-Close monitoring of HBV DNA and LFT post-transplantation and treat accordingly. References:
1- British Transplantation Society Guidelines: Guidelines for Hepatitis B & Solid Organ Transplantation 2018.
2-Veroux M, Ardita V, Corona D, et al. Kidney Transplantation From Donors with Hepatitis B. Med Sci Monit. 2016;22:1427-1434. Published 2016 Apr 28. doi:10.12659/msm.896048.
I will accept the donation. If the recipient is negative for HB s antigen and HBs antibodies then transplant can be planned with HBV immunoglobuline and Lamivudine prophylaxis.
If recipient is positive for Hbs antigen then transplantation with treatment protocol depending on other parameters of HBV DNA and HBVe antigen level to determine the suitable protocol of treatment.
HBe ang positive donor indicate active replication of the virus . Transplanting from such a donor is bearing high risk of infection in HBV naive recipient and its highly indicated to administer both HBIG and Lamivudine prophylaxis.
If the recipient is immunized with HBV antibodies titer of more than 100 then transplanting a kidney from HBs ag positive/HBV DNA negative donor can proceed transplantation with no prophylaxis but with close follow up.
You were offered kidneys from a 53-year-old male DBD (donor after brain stem death) donor who suffered from SAH (grade 5) complicating cerebral aneurysm. His retrieval S Cr was 78 µmol/L. Virology was reported as follows: HBsAg positive, HBsAb negative, HBcAb negative, both HBeAg and HBeAb are negative. Both HCV and HIV are negative;
Will you accept this DBD donor?
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
What is your differential diagnosis?
How would you manage this case?
NDD w Virology was reported as follows:
HBsAg + ve HBs Ab -ve , HBc Ab -ve
HBe Ag -ve , HBe Ab -ve
HCV -ve , HIV -ve
We need Donor HDV Ab serology and HBV DNA levels.
Before we accept the HBsAg positive donor, better to know the immune status of the recipient.
Will you accept this DBD donor?
Yes, but depending on recipient HBV status;
If recipient is vaccinated with anti HBs titer is more than 10 mIU/ml.
If Had chronic infection in past with lifelong antiviral therapy.
If Prior infection and immunity with antiviral therapy during intense IS.
YES, After Signing Exceptional Distribution Risk Consent (ExD) =>
If no immunity or not vaccinated, would need immunoglobulins and antiviral therapy if transplant occurred. HBV DNA, HBsAg and anti HBc should be checked every 3 months.
The non-liver solid organs of the HBsAg positive organ donor can be used for any recipient, after an individualized assessment of risk and benefit. (2C)
Individuals undergoing non-liver solid organ transplantation who are HBsAg positive must have liver disease staging and suppression of HBV DNA by either Tenofovir or Entecavir before transplantation if there is a standard clinical indication. (1B)
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
YES,
I will accept if HBs Ag positive Donor to HBsAg positive recipient,
Individuals undergoing non-liver solid organ transplantation who are HBsAg positive must have liver disease staging and suppression of HBV DNA by either Tenofovir or Entecavir before transplantation if there is a standard clinical indication. (1B)
HBsAg positive donors should not be used for HBV/HDV co-infected recipients. (1C)
It willneed lifelong antiviral therapy if the recipient is established chronic infection, to do so will have to do Anti HBs, Ant HBc antibodies and DNA PCR.
In case of live donor HBV negative recipient should be vaccinated prior to transplantation. HBV DNA, HBsAg and anti HBc should be checked every 3 months.
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
YES,
Management will be changed; because this high risk for HBV recurrence. (HBeAg) and (anti-HBe or HBeAb);
Useful in monitoring chronic HBV infection, especially during antiviral therapy.
The presence of HBeAg relates to viral replication.
Patients with HBeAg are generally considered to be more infectious than those with anti-HBe and without HBeAg.
Life-long combination therapy with HBIG and a potent NA can potentially be given to patients who were traditionally considered at high risk for HBV recurrence. (2B)
Individuals with decompensated cirrhosis and detectable HBV DNA require urgent antiviral treatment with NA(s). Entecavir and tenofovir are the first line antiviral agents and should be continued indefinitely. (1A)
Individuals with decompensated cirrhosis due to hepatitis B should be treated in specialist liver units as the application of antiviral therapy is complex and these patients may be candidates for liver transplantation. (1C)
Patients with advanced HBV-related liver disease requiring another organ transplant be considered for combined transplantation after careful consideration of the potential risks and benefits. (2C)
What is your differential diagnosis?
Considered at high risk for HBV recurrence,
HBe Ag positive patients,
HBV DNA positive at time of transplant,
Those transplanted for hepato-cellular carcinoma or,
Those who are HIV co-infected.
How would you manage this case?
In HBsAg positive individuals deemed to be at high risk of recurrence, combination therapy with HBIg and/or a potent NA is recommended from the time of transplantation to prevent HBV reinfection post-liver transplant. (1B)
Individuals with fulminant liver failure associated with hepatitis B infection must be managed in a specialist liver centre. (1C)
HBV/HDV recipients should receive combination HBIg/NA prophylaxis from time of transplantation. (1C)
For HBV/HDV infected recipients HBIg withdrawal from combination HBIg/nucleo(t)side analogues (NA) prophylaxis can be considered, but not within 12 months of transplantation. (2C)
HBV DNA and HBsAg should be monitored every three months in the first year and thereafter every six months in HBsAg positive liver transplant recipients or individuals receiving a graft from a HBcAb positive donor, regardless of treatment or prophylaxis regimen. (1C)
Amongst renal transplant recipients who are HBcAb positive, if HBsAb are < 100 IU/mL, then vaccination should be considered to boost the protective titre of HBsAb and minimize the risk of reactivation. (2C)
In those who fail to respond to the initial HBV vaccination schedule, a second series should be administered. (2C)
References;
*British Transplantation Society Guidelines: March 2018.
I like your well structured detailed summary. I appreciate level of recommendation in relation to each advice in relation to the type of disease and corresponding mode of treatment indicated.
Typing whole sentence in bold amounts to shouting.
Chronic HBV is not uncommon and its prevalence vary according to the region ranging from 1.2-2.6% in Europe and up to 4.6-7.6% in Africa
Goal of management
In HBV negative recipient who receive HBV positive kidney with chronic (HBsAg positive, anti-HBc positive) or previous infection (HBsAg negative, anti-HBc positive), the primary goal is to prevent deovo infection which is rare except if HBsAg is positive, PCR is high, and there is residual donor blood containing HBV in the kidney since HBV is does not residue in the kidney
In HBV positive recipient with chronic (HBsAg positive, anti-HBc positive) or previous infection (HBsAg negative, anti-HBc positive), the primary goal is to prevent reactivation of the HBV related liver disease since the HBV is present in the liver tissue even after disappearance of HBs Ag
Transplant recipient evaluation with positive HBsAg
Transplant recipient who are HBsAg positive (chronic HBV) should do HBeAg, HBV PCR and should be evaluated for the presence of cirrhosis
Presence of compensated cirrhosis is not considered a contraindication to transplantation, and transplantation can be done under cover of antiviral with comparable outcome to HBV negative recipient (1,2)
Patients with decompensated cirrhosis are candidates for dual liver and kidney transplantation
Donor evaluation
There may be a possible risk to the donor since HBV is associated with the possibility of glomerulonephritis and PAN which can have bad impact on the kidney
Transmission of infection from the donor to the recipient is rare except if HBsAg is positive, PCR is high, and there is residual donor blood containing HBV in the kidney since HBV is does not residue in the kidney
Active HBV infection is considered a contraindication to donation, as there are reported cases of fulminant hepatitis after transplantation from donors who were HBsAg and HBeAg positive.
Approach for transplanting kidney from HBsAg positive donor to naive transplant recipient
The main challenge is transmission of HBV from donor to the recipient which is lower in kidney compared to liver transplantation but still can occur so the following approach should be done in order to improve outcome:
A- Evaluation of the donor risk
Treatment of the donor and providing functional cure (sustained absence of HBsAg with or without the development of anti-HBs) before transplantation is the best
Donor with HBsAg (+)/ PCR (-) (< 20 IU/mL) is associated with minimal risk if transplanted to immune recipient (antiHBs + ) especially if the antiHBs + titer is protective
Donor with HBsAg (+)/ PCR (+) is associated with the highest risk if transplanted to non-immune recipient (antiHBs < 10 )
B- Selecting the appropriate recipient
Vaccination : IM (SC route may give better results) injection of 3 to 4 doses of either Recombivax or Engerix B vaccine, given at 0, 1, 2(if using Engerix B) and 6 months, it is mandatory for patients with antiHBs < 10 and the target is to reach a protective titer of > 10 mIU/mL, this level may be difficult to reach in ESRD especially those of HD , if the level is not reached an additional 3 doses should be given
Patient should have normal liver function tests
No pervious history of liver disease in the past month
Living in areas not known to have mutant strains of HBV
Low immunological risk status to avoid aggressive immunosuppression
Recipient should not have HCV co-infection or other liver disease
Urgent need for transplantation such as those with no vascular access, inadequate dialysis or recipients who have contraindications to dialysis
Recipients with expected very long time on waiting list
C- Use of prophylactic therapy at the time of transplantation including
HBIG that act as a neutralizing antibodies
Antiviral medication that suppress HBV replication which includes : Lamivudine (less effective, higher resistance) (3-5), enticaver which is the drug of choice as it is not nephrotoxic and only needs renal dose adjustment), tenofovir which is preferred in patients with history of lamuvidine use before, tenofovir alafenamide is preferred to tenofovir disoproxil fumarate due to lower renal toxicity assocauted with this drug)
Pegylated interferon alfa should not be used in renal transplant recipients since it may cause graft rejection
Prophylaxis is indicated in the following
Patients with antiHBs < 10 receiving kidney from HBs Ag (+)/HBV DNA (-) donors should receive antiviral monotherapy for at least 1 year
Patients with antiHBs < 10 receiving HBsAg (+)/HBV DNA (+) donor kidney carry the highest risk of seroconversion and should be declined but if transplanted they should receive both antiviral and HBIG
Patients with antiHBs ≻ 10 receiving kidney from HBsAg (+)/HBV DNA (-) donor should receive either no (if antiHBs ≻ 100) or antiviral monotherapy for at least 1 year
Patients with antiHBs ≻ 10 receiving HBsAg (+)/HBV DNA (+) donor kidney should receive prophylaxis using antiviral with or without HBIG
D- Monitoring
Regular check of serum ALT, HBV DNA, HBsAg and anti-HBc every 3 months in the first year post transplantation, if remain negative, antiviral medications should be stopped and testing should be done annually
Monitoring of antiHBs Ab yearly, and if < 10 a booster dose should be given, an anti-HBs titer >100 mIU/mL is associated with the lowest risk of denovo infection if patient receive kidney from HBsAg-positive donors (6).
Denovo infection is diagnosed once there is detectable HBV DNA, positive anti-HBc or positive HBsAg
Prerequisites before accepting HBV positive donor to an HBV naive recipient:
The recipient should be vaccinated with antiHBs ≻10
Recipient should be willing to take an infected kidney
Compliance to antiviral drugs and follow up should be ensured
The recipient should be in urgent need for a graft (those with no vascular access or those with expected very long time on waiting list)
The recipient should have no history of liver disease with normal liver function tests
Standard immunological risk status is required to avoid aggressive immunosuppression
Recipient should have no HCV co-infection
The donor PCR and HBe antigen are negative
As these criteria will put the patient at minimal risk of reactivation with either no or single antiviral agent for at least 1 year with close follows up every 3 months, except if the recipient is HBV positive at this situation I will initiate treatment before transplantation
Approach for transplanting kidney to transplant recipient with chronic (HBsAg positive, anti-HBc positive)
Transplant recipients with chronic infection can receive kidney from any donor regardless of HBV status
Transplant recipients with chronic infection should receive lifelong antiviral therapy at the time of transplantation
HBsAg positive transplant recipients are at higher risk of reactivation compared to those with previous infection (HBsAg negative, anti-HBc positive), the risk of reactivation in patients with previous infection was estimated to be 3.4% without antiviral therapy (7)
In patients with chronic infection regular check of serum ALT, HBV DNA is indicated every 6 months
Reactivation is diagnosed once there is detectable HBV DNA, increase PCR by > 1 log or positive HBsAg (in case of previous infection)
Hepatitis flare is diagnosed once there is elevation of serum ALT more than 3 times the ULN
Patients who develop reactivation or flare while on antiviral therapy, we have to check for adherence, dosage or drug resistance (rare with entecavir or tenofovir) or search for other cause of hepatitis
To conclude
I will do PCR for the donor and antiHBs to the recipient to evaluate the risk, if PCR is positive I will exclude this donor. If PCR is negative I will accept this DBD donor under the following circumstances
The recipient should be vaccinated with antiHBs ≻10
Recipient should be willing to take an infected kidney
Compliance to antiviral drugs and follow up should be ensured
The recipient should be in urgent need for a graft (those with no vascular access or those with expected very long time on waiting list)
The recipient should have no history of liver disease with normal liver function tests
Standard immunological risk status is required to avoid aggressive immunosuppression
Recipient should have no HCV co-infection
Antiviral and HBIG prophylaxis should be received according to the indications mentioned before
On the other hand, I will you accept this donor as a live donor if the recipient is also HBsAg positive since transplant recipients with chronic infection can receive kidney from any donor regardless of HBV status under cover of life long antiviral therapy with close monitoring, provided that there is no or compensated cirrhosis,
In case of decompensated cirrhosis , patient will be candidate for dual transplantation
An impotent point to be put in mind is that the risk on the donor since there is a possible risk of glomerulonephritis and PANS which can have bad impact on the kidney
If the donor HBeAg is positive in addition to positive HBsAg at that time I will exclude this donor since there are reported cases of fulminant hepatitis after transplantation from donors who were HBsAg and HBeAg positive.
References
1- Chan TM, Fang GX, Tang CS, et al. Preemptive lamivudine therapy based on HBV DNA level in HBsAg-positive kidney allograft recipients. Hepatology 2002; 36:1246.
2- Yap DY, Tang CS, Yung S, et al. Long-term outcome of renal transplant recipients with chronic hepatitis B infection-impact of antiviral treatments. Transplantation 2010; 90:325.
3- Liaw YF, Sung JJ, Chow WC, et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med 2004; 351:1521.
4- Loomba R, Rowley A, Wesley R, et al. Systematic review: the effect of preventive lamivudine on hepatitis B reactivation during chemotherapy. Ann Intern Med 2008; 148:519.
5- Han DJ, Kim TH, Park SK, et al. Results on preemptive or prophylactic treatment of lamivudine in HBsAg (+) renal allograft recipients: comparison with salvage treatment after hepatic dysfunction with HBV recurrence. Transplantation 2001; 71:387.
6- Chancharoenthana W, Townamchai N, Pongpirul K, et al. The outcomes of kidney transplantation in hepatitis B surface antigen (HBsAg)-negative recipients receiving graft from HBsAg-positive donors: a retrospective, propensity score-matched study. Am J Transplant 2014; 14:2814.
7- Shaikh SA, Kahn J, Aksentijevic A, et al. A multicenter evaluation of hepatitis B reactivation with and without antiviral prophylaxis after kidney transplantation. Transpl Infect Dis 2022; 24:e13751.
I like your analysis. However, you mention as I quote you, “Treatment of the donor and providing functional cure (sustained absence of HBsAg with or without the development of anti-HBs) before transplantation is the best.” Do you really have enough time to treat DBD donor with anti-viral ?
4. You were offered kidneys from a 53-year-old male DBD (donor after brain stem death) donor who suffered from SAH (grade 5) complicating cerebral aneurysm. His retrieval S Cr was 78 µmol/L. Virology was reported as follows: HBsAg positive, HBsAb negative, HBcAb negative, both HBeAg and HBeAb are negative. Both HCV and HIV are negative.
==================================================================== History
A 53-year-old male DBD donor donated kidneys from SAH with 78 µmol/L, HBsAg positive,HBsAb negative, HBcAb negative, HBeAg and HBeAb negative, HCV and HIV negative.
==================================================================== Will you accept this DBD donor?
HBsAg positive, HBsAb negative, HBcAb negative
Both HBeAg and HBeAb are negative.
Both HCV and HIV are negative.
Yes I will accept this donor
D(HBsAg+)/R(HBsAg-) should be considered for living kidney transplantation, but with extra caution on donors with HBV DNA+ and male candidates.
Transplantation of a non-liver solid organ from an HBsAg positive donor to a non-immune recipient can lead to chronic infection.
Antivirals should be given to prevent HBV-related liver damage.
Low-risk hepatitis B surface antigen (HBsAg) positive kidney donors should be allocated to immune-recipients with anti-HBs at least 10 mIU/mL to reduce risk of transmission.
==================================================================== Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
Yes
Absolutely, it is necessary to check the donor’s viremia with HBV DNA beforehand; if it is positive, it is preferable to treat the donor before the donation.
Can be donated to an immune recipient (natural or immunized) if the HBV DNA test is negative.
Patients receiving kidney transplants from HBsAg-positive, HBV-DNA positive donors exhibited similar graft and patient survival, acute rejection, and post-transplant sequelae to those receiving HBsAg-negative kidneys, despite a higher incidence of acute hepatitis.
These studies shown that in HBsAg-positive kidney transplants, protective HBV immunity from prior infections or vaccinations prevented chronic HBV infection.
Although NA antivirals (entecavir and tenofovir) may suppress HBV long-term and prevent cirrhosis and liver failure, transplanting HBsAg-positive kidneys into HBV-naive recipients runs the risk of causing primary infection.
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
A modification in management will be made due to the significant risk of HBV recurrence.
HBeAg and anti-HBe or HBeAbImportant for tracking chronic HBV infection, particularly when receiving antiviral medication.
HBeAg is associated with viral replication.
Generally, patients with HBeAg are thought to be more contagious than those with anti-HBe and without HBeAg.
Patients who were previously thought to be at high risk for HBV recurrence may benefit from lifetime combination therapy with HBIG and a strong NA.
Patients with decompensated cirrhosis and HBV DNA that can be detected need to start taking NA right away .
First-line antiviral treatments should always include entecavir and tenofovir.
================================================================== What is your differential diagnosis?
Chronic HBV infection
For HBsAg, results can be mistakenly positive.
Hepatitis D and B virus infections can happen at the same time.
==================================================================== How would you manage this case?
A hepatology consultation can help inform the receiver of the risk of HBsAg-positived organs, administer pre-transplant immunization, and perform transplants.
A blood sample for PCR HBV DNA-donor .
Post-transplant prophylaxis and monitoring of liver enzymes and viral load.
Yilmaz VT, Ulger BV, Aliosmanoglu İ, Erbis H, Tuna Y, Akbas H, et al. Assessment of long-term outcomes in Hbs Ag-negative renal transplant recipients transplanted from Hbs Ag-positive donors. Ann Transplant. 2015;20:390–6.
Veroux M, Ardita V, Corona D, et al. Kidney Transplantation From Donors with Hepatitis B. Med Sci Monit. 2016;22:1427-1434. Published 2016 Apr 28. doi:10.12659/msm.896048
Srisuwarn P, Sumethkul V. Kidney transplant from donors with hepatitis B: A challenging treatment option. World J Hepatol. 2021;13(8):853-867. doi:10.4254/wjh.v13.i8.853
British Transplantation Society GuidelinesGuidelines for Hepatitis B & Solid Organ Transplantation.
I like your analysis. However, you mention as I quote you, “HBV DNA beforehand; if it is positive, it is preferable to treat the donor before the donation.” Do you really have enough time to treat DBD donor with anti-viral ?
This DBD has isolated positive Hbs Ag and negative other antibodies so we should consider one of the following: – Early hepatitis HBV infection or Hepatitis D co-infection with HBV – False positive HBsAg results An HBV-negative recipient could only receive a kidney transplant from a HbsAg-positive donor in extreme circumstances. There is a high probability of de novo infection with HBsAg-positive allografts in HBsAg-negative recipients. Will accept the kidney donation if: – Recipient is Hbs Ag positive – If long time on the waiting list – If recipient accept to take the risk of transplantation from Hbs Ag patient, being advised to take the treatment Before kidney transplantation quantitative PCR HBV DNA is needed to look for viremia load.
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
Living donors who have positive Hbs Ag should have their viral loads confirmed by PCR HBV DNA. If this is the case, the donor should be treated before donating, and the efficacy of the therapy should be confirmed. Patients receiving kidney transplants from HBsAg-positive, HBV-DNA positive donors exhibited similar graft and patient survival, acute rejection, and post-transplant sequelae to those receiving HBsAg-negative kidneys, despite a higher incidence of acute hepatitis.
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
In this context, the current clinical condition of donor is active hepatitis B infection which indicates that transplantation of donor with active Hep B carries high risk of infection transmission into immunocompromised patient. In this case donation is only given to waitlisted Hep B positive recipient on treatment or if the patient accepted the risk of infection.
What is your differential diagnosis?
This DBD has isolated positive Hbs Ag and negative other antibodies so we should consider one of the following: o Early hepatitis HBV infection or Hepatitis D co-infection with HBV o False positive HBsAg results
How would you manage this case?
– Blood sample for PCR HBV DNA
– Donor Liver biopsy would be of great value for confirmation of Hepatitis B infection, during organ retrieval.
– Pre-transplant vaccination of recipient
– Prophylaxis with lamivudine or entecavir post-transplantation
– Monitoring of liver enzymes and viral load after transplantation
I like your analysis. However, you mention as I quote you, “PCR HBV DNA. If this is the case, the donor should be treated before donating, and the efficacy of the therapy should be confirmed..” Do you really have enough time to treat DBD donor with anti-viral ?
Thank you Dr for your comment. In regards to PCR HBV DNA, needed to confirm the viral load and nor for treatment, in other words, to assess the risk of infection activation after transplantation.
However for living donation, it is used as baseline and for followup on treatment.
Previous serology (HBsAg, anti-HBs, HBcAg, anti-HBc, HBeAg) and the HBV DNA result of the donor are satisfactory OR
No recent history of viral hepatitis in the recipient
IF the recipient consented to have the organ after proper and detailed education has been done for him on the nature of the organ and the prognosis.
Involvement of hepatitis specialist in counseling the patient and part of the MDT
HBsAg positive organ has been included in extended criteria for organ donation because of a gross imbalance between kidneys needed and those available for transplantation. Moreso, this is a diseased donation, there is no sufficient time to start running a further investigation on the donor. Although blood samples can be collected for a retrospective test like HEV RNA, anti-HBe, and HBV DNA
2) Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met
In this situation, there is no concern of cold ischemic time on the kidney allograft, hence full serological, NAT, and HBV DNA will be done on both the donor and the recipient. This should be followed with NA treatment until the HBV DNA level is undetected if it was high initially
The following condition must be met:
Absence of HBV+ HDV co-infection in the recipient
Undetected HBV DNA level in both the recipient and the donor as several studies revealed that the prevalence of hepatitis B viremia in HBsAg (+)/HBeAg (-) donors ranged from 2.3%-28.3%
Presence of anti-HBs > 10mUI/ml in the recipient following treatment with NA
Normal eleven of liver transaminases
3)Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
This donor has an active infection with possible ongoing replication of HBV because of positive HBeAg. However, acute infection is usually diagnosed by positive HBsAg, clinical symptoms, and high aminotransferase of more than x 3 upper normal level
No, it will change.
4) What is your differential diagnosis
the early stage of HBV infection
acute on chronic infection
HBV and HDV co-infection
5) How would you manage this case?
properly informed consent will be obtained from the recipient
Prophylactic with BHIG and a potent NA will be administered immediately after the KT, although this kind of situation is only encouraged in urgent need for kidney transplantation as a result of exhaustion of vascular access or ongoing uremia despite adequate dialysis.
Close monitoring of HBV serology and HBV DNA every 3 months in the first year post-KTP, then every 6 months
Regular liver function test
If possible avoid Rituximab as induction, desensitization, and in acute rejection secondary to ABR
Keep immunosuppression at the lowest dose to prevent rejection
References
BTS Guidelines for Hepatitis B and Solid Organ Transplantation
Chancharoenthana W, Townamchai N, Pongpirul K, Kittiskulnam P, Leelahavanichkul A, et al. The outcomes of kidney transplantation in hepatitis B surface antigen (HBsAg)-negative recipients receiving graft from HBsAg-positive donors: a retrospective, propensity score-matched study. Am J Transplant 2014; 14: 2814-2820.
Jiang H, Wu J, Zhang X, Wu D, Huang H, et al. transplantation from hepatitis B surface antigen positive donors into hepatitis B surface antibody positive recipients: a prospective nonrandomized controlled study from a single center. Am J Transplant 2009; 9: 1853-1858.
Praopilad Srisuwarn, Vasant Sumethku. Kidney transplant from donors with hepatitis B: A challenging treatment option. World J Hepatol. 2021;13(8): 853-857
Jeong Eun Song, Do Young Kim. Diagnosis of Hepatitis B. Ann Transl Med. 2016; 4(18): 338
Remember HBcAg is only in the hepatocyte.
HBeAg means viral replication so this is a highly infective situation confirmed by a PCR, to be accepted in EMERGENCY situation after counselling.
Only in emergencies could a kidney from a HbsAg-positive donor be transplanted into an HBV-negative recipient.
HBsAg-positive allografts in HBsAg-negative recipients have a high risk of de novo infection. Most transplant hospitals do not transfer kidneys from HBsAg-positive donors, and in most countries, these donors may only be transplanted into matched HBsAg-positive recipients.
Most studies have shown that transplanting HBsAg-positive kidneys to recipients with natural immunity is safe and reasonable.
In recent research, we reported 5 successful kidney transplantations from HBsAg-positive donors to HBsAg-positive recipients with no post-transplant transaminase increase and a considerable decrease in waiting time.
Only in emergencies could a kidney from a HbsAg-positive donor be transplanted into an HBV-negative recipient.
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
Yes, First the donor should have HBV DNA to check the viremia, if it is positive, better to treat the donor before the donation
If HBV DNA is negative, the kidney can be given to an immune recipient (natural or vaccinated.
Despite a greater occurrence of acute hepatitis, kidney transplant patients of HBsAg-positive, HBV-DNA positive donors had comparable graft and patient survival, acute rejection, and post-transplant sequelae to those of HBsAg-negative kidneys.
These investigations showed that protective HBV immunity from past infection or immunization prevents chronic HBV infection in HBsAg-positive kidney recipients.
HBsAg-positive kidneys transplanted into HBV-naïve recipients may cause primary infection, although NA antivirals (entecavir and tenofovir) may suppress HBV long-term and avoid cirrhosis and liver failure. Hepatocellular carcinoma risk remains increased for these people.
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
The donor has active HBV infection, the same acceptance rules Only in emergencies could a kidney from a HbsAg-positive donor be transplanted into an HBV-negative recipient. If the recipient accepts the risk:
The recipient should be treated with HBIg and NA directly post-transplantation.
What is your differential diagnosis?
chronic infected HBV
Results can be falsely positive for HBsAg
Infection with hepatitis D and hepatitis B viruses may occur simultaneously.
How would you manage this case?
Take care of it with the help of a hepatology consultation.
counseling the recipient of the possibility of HBsAg-positive organs
A pre-transplant vaccine booster should be administered
Continue with the transplanting procedure.
start lamivudine or entecavir directly
close monitoring of HBV DNA and LFT post-transplantation.
References: Veroux, M., Ardita, V., Corona, D., Giaquinta, A., Ekser, B., Sinagra, N., … & Veroux, P. (2016). Kidney transplantation from donors with hepatitis B. Medical Science Monitor: International Medical Journal of Experimental and Clinical Research, 22, 1427.
Yes, as DBD per say he has no absolute contraindication to donation. Due to HBsAg positivity, assessments of risk versus balance must be considered for non-liver solid organ recipient but these serology results are not making sense to me because he had only HBsAg positive and other serology were negative. It could be an early HBV infection but no information about HBV DNA. If he had acute HBV infection we would have gotten anti-HBcIgM positive or in case of chronic hepatitis B, I would expect anti-HBcIgG positive. How ever his HBcAb were negative, no HBV DNA results , and HBVsAg was positive. HBsAg alone may be false positive, so in ideal situation this serology need to be verified further because we cannot put it together and there was no HBV DNA given. This may not be possible in deceased donor set up.
-Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
Yes, I will accept him as long as the recipient is HDV negative
Even in HBsAg negative recipient , this donor can be accepted in in urgency situation
Recipient should be treated with entecavir or tenofovir from the time of transplantation
-Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
No, the management remained the same regardless the DBD donor HBeAg/Ab status i.e., I will accept the DBD donor, the recipient must counseled and get entecavir or tenofovir right away from the time of transplantation.
-What is your differential diagnosis?
Early hepatitis HBV infection
False positive HBsAg results
Hepatitis D infection may co-exist with HBV
-How would you manage this case?
Manage with the assistance from the liver specialist unit
Counseling of the recipient about HBsAg +ve organ
Make sure the recipient is HDV negative before to proceed
Proceed with transplantation
Entecavir or tenofovir prophylaxis should be given to the recipient from the time of transplantation
Monitoring for any evidence of HBV reactivation or HBV flare
You correctly mentioned that in a DD you usually have no times for the rest of useful investigation but it is always wise is to store blood samples from the donor.
HB e AG means active viral replication,so you should take it from there.
The donor is HBsAg positive, HBsAb negative, HBcAb negative, both HBeAg and HBeAb are negative
The donor should undergo HDV Ab serology and HBV DNA levels.
Before we accept the HBsAg positive donor, we need to know the immune status of the recipient.
“Transplantation of a non-liver solid organ from an HBsAg positive donor to a non-immune recipient will result in chronic infection of the recipient. In this setting, antivirals should be given to prevent HBV-related liver damage.”
HBV Vaccination
All prospective solid organ transplant recipients who are HBV naive must be vaccinated (time permitting) and the response documented. (1C)
Amongst renal transplant recipients who are HBcAb positive, if HBsAb are <100 IU/mL, then vaccination should be considered to boost the protective titre of HBsAb and minimise the risk of reactivation. (2C)
All prospective solid organ transplant recipients should receive a high-dose, accelerated vaccine schedule. (2C)
In those who fail to respond to the initial HBV vaccination schedule, a second series should be administered. (2C)
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
If the recipient is also HBsAg positive then he should undergo HDV Ab serology, and HBV DNA levels.
If the recipient has HBV DNA detectable, then he should be appropriately treated with anti-virals.
“Individuals undergoing non-liver solid organ transplantation who are HBsAg positive must have liver disease staging and suppression of HBV DNA by either tenofovir or entecavir before transplantation if there is a standard clinical indication. (1B)”
If the recipient is HDV co-infected, then we cannot accept the HBsAg positive donor.
“HBsAg positive donors should not be used for HBV/HDV co-infected recipients.”
The donation of non-liver solid organs from an HBsAg positive donor to an HBsAg positive recipient can be undertaken as long as antivirals are used to suppress HBV after transplantation.
In this setting, there appears to be no adverse impact on graft or patient survival.
There is a significant published literature describing the outcome of HBsAg positive kidney donation to HBV immune recipients.
Monitoring for HBV Recurrence or De Novo Infection
HBV DNA and HBsAg should be monitored every three months in the first year and thereafter every six months in HBsAg positive transplant recipients or individuals receiving a graft, regardless of treatment or prophylaxis regimen. (1C)
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
If HBeAg and HBeAb are positive in addition to positive HBsAg, then its active hepatitis B infection, which needs to be treated before transplanted.
McPherson S, Elsharkawy AM, Ankcorn M, Ijaz S, Powell J, Rowe I, Tedder R, Andrews PA. Summary of the British Transplantation Society UK guidelines for hepatitis E and solid organ transplantation. Transplantation. 2018 Jan
Typing whole sentence in bold amounts to shouting.
I like your well structured detailed summary. I appreciate level of recommendation in relation to each advice in relation to the type of disease and corresponding treatment.
Interpretation of current case; according virology report; -HBsAg (positive) , HBsAb (negative) , HBcAb (negative) -HBeAg (negative) , HBeAb (negative) -HCV (negative) , HIV (negative) -Considering this patient (non-immune chronically infected HBV) and need further investigations (LFTs,HBV PCR,HDV&HEV serology,U/S Liver) 1-Will you accept this DBD donor? Yes; I will accept this donor (after informed consent of high risk for transmission of infection) According to British Transplantation Society Guidelines:March 2018;
-If need demands, the non-liver solid organs of the HBsAg positive organ donor can be used for any recipient, after an individualised assessment of risk and benefit. (2C)
-Individuals undergoing non-liver solid organ transplantation who are HBsAg positive must have liver disease staging and suppression of HBV DNA by either tenofovir or entecavir before transplantation if there is a standard clinical indication. (1B) 2-Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met? Yes; I will accept if HBs positive Doner to HBsAg positive recipient; According to British Transplantation Society Guidelines:March 2018;
-Individuals undergoing non-liver solid organ transplantation who are HBsAg positive must have liver disease staging and suppression of HBV DNA by either tenofovir or entecavir before transplantation if there is a standard clinical indication. (1B)
-HBsAg positive donors should not be used for HBV/HDV co-infected recipients. (1C) 3-Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management? Yes; management will be changed; because this high risk for HBV recurrence.
(HBeAg) and (anti-HBe or HBeAb);
-Useful in monitoring chronic HBV infection, especially during antiviral therapy.
-The presence of HBeAg relates to viral replication.
-Patients with HBeAg are generally considered to be more infectious than those with anti-HBe and without HBeAg. According to British Transplantation Society Guidelines:March 2018;
-Life-long combination therapy with HBIG and a potent NA can potentially be given to patients who were traditionally considered at high risk for HBV recurrence. (2B) –Individuals with decompensated cirrhosis and detectable HBV DNA require urgent antiviral treatment with NA(s). Entecavir and tenofovir are the first line antiviral agents and should be continued indefinitely. (1A)
-Individuals with decompensated cirrhosis due to hepatitis B should be treated in specialist liver units as the application of antiviral therapy is complex and these patients may be candidates for liver transplantation. (1C)
-Patients with advanced HBV-related liver disease requiring another organ transplant be considered for combined transplantation after careful consideration of the potential risks and benefits. (2C) 4-What is your differential diagnosis? Considered at high risk for HBV recurrence;
-HBeAg positive patients,
-HBV DNA positive at time of transplant,
-Those transplanted for hepatocellular carcinoma or,
-Those who are HIV co-infected. 5-How would you manage this case? According to British Transplantation Society Guidelines:March 2018;
-In HBsAg positive individuals deemed to be at high risk of recurrence, combination therapy with HBIg and/or a potent NA is recommended from the time of transplantation to prevent HBV reinfection post-liver transplant. (1B)
-Individuals with fulminant liver failure associated with hepatitis B infection must be managed in a specialist liver centre. (1C)
-HBV/HDV recipients should receive combination HBIg/NA prophylaxis from time of transplantation. (1C)
-For HBV/HDV infected recipients HBIg withdrawal from combination HBIg/nucleo(t)side analogues(NA) prophylaxis can be considered, but not within 12 months of transplantation. (2C)
-HBV DNA and HBsAg should be monitored every three months in the first year and thereafter every six months in HBsAg positive liver transplant recipients or individuals receiving a graft from a HBcAb positive donor, regardless of treatment or prophylaxis regimen. (1C)
-Amongst renal transplant recipients who are HBcAb positive, if HBsAb are < 100 IU/mL, then vaccination should be considered to boost the protective titre of HBsAb and minimise the risk of reactivation. (2C)
-In those who fail to respond to the initial HBV vaccination schedule, a second series should be administered. (2C) References; British Transplantation Society Guidelines:March 2018;
I like your well structured detailed summary. I appreciate level of recommendation in relation to each advice in relation to the type of disease and corresponding treatment.
Yes but depending on recipient HBV status; · If recipient is vaccinated with anti HBs titer is more than 10 mIU/ml. · Had chronic infection in past with lifelong antiviral therapy. · Prior infection and immunity with antiviral therapy during intense IS. NO if no immunity or not vaccinated, would need immunoglobulin’s and antiviral therapy if transplant occurred. HBV DNA, HBsAg and anti HBc should be checke every 3 months · Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
Yes but would need lifelong antiviral therapy if the recipient is established chronic infection, to do so will have to do Anti HBs, Ant HBc antibodies and DNA PCR. In case of live donor HBV negative recipient should be vaccinated prior to transplantation. HBV DNA, HBsAg and anti HBc should be checke every 3 months · Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
No will manage on the same line.
· How would you manage this case?
· Recipient is immunized by vaccination than measure titer prior to transplantation if titer is less than 100mIU/ml than may consider immunoglobulin and antiviral therapy for upto 1 year. · Recipient who had prior infection need to have antiviral indefinitely. · No immunity to HBV or no previous exposure of recipient ideally avoids graft from HBsAg positive (chronic infection) donors. But if occurred (compelling reasons) than immunoglobulin with antiviral and vaccination. Though response to vaccination in recipients who are on maintenance Immunosuppressant is poor.
Will do HBV DNA Yes Provided Anti- Hbs = or > 10 IU/L in the receipient No If Anti- Hbs < 10 IU/L in the receipient Will accept along with 12 months of nucleotide antiviral prophylaxis along with HBIG when receipient is Naïve or Anti- Hbs < 10 IU/L only if urgent need for KT (exhausted multiple vascular access,with ongoing uremia despite adequate hemodialysis prescription).
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
Yes will accept as donor provided, Receipient should have – no abnormalities of liver function test no history of liver disease within the previous 28 days who are not living in the area of possible mutation strain of HBV result of liver biopsy that did not show evidence of cirrhosis. received antiviral treatment
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
Will discard the organ .
What is your differential diagnosis?
There may be instances where HBsAg may be momentarily positive within 30 days of receiving a dose of the hepatitis B vaccine. HBV DNA needs to be done to rule out infection. In the index case HBsAg positive, HBsAb negative, HBcAb negative, both HBeAg and HBeAb are negative.So recent vaccination with Hep B vaccine needs to be asked for. Other possibility is wrong report. Interpretation of hepatitis B serology report- HBsAg—Positive Total anti-HBc — Positive IgM anti-HBc — Positive Anti-HBs — Negative Then Acute infection HBsAg — Positive Total anti-HBc — Positive IgM anti-HBc — Negative Anti-HBs — Negative Then Chronic Infection HBsAg — Negative Total anti-HBc — Positive Anti-HBs — Positive Then Resolved Infection HBsAg — Negative Total anti-HBc — Negative Anti-HBs — Positive Immune from receipt of prior vaccination (if documented complete series) HBsAg — Negative Total anti-HBc — Positive Anti-HBs — Negative So when Only core antibody is positive, then Resolved infection where anti-HBs levels have waned Occult Infection Passive transfer of anti-HBc to an infant born to an HBsAg-positive gestational parent A false positive, thus patient is susceptible A mutant HBsAg strain that is not detectable by laboratory assay HBsAg — Negative Total anti-HBc — Negative Anti-HBs — Negative Then Susceptible, never infected (if no documentation of HepB vaccine series completion)
How would you manage this case?
monitoring liver enzymes, HBsAg, and HBV DNA every 3 months for at least 12 months post-transplantation and then yearly. monitoring of anti-HBs concentration should be done at least yearly. If Anti HBs (<10 mIU/mL) a total complete course of vaccination with a follow-up level at 4-wk after a complete course of treatment. Anti HBs (+ or > 10 mIU/mL) ,then lamivudine or entecavir for 12 months post transplantation . Anti HBs (> 100 mIU/mL),then lamivudine or entecavir for 6 months post transplantation . Anti HBs (> 10 mIU/mL) and positive recipients can receive kidney transplants from anti-HBc (+) donors without a need for prophylaxis antiviral medications due to the negligible risk of HBV transmission.
In contrast, naïve recipients who received kidneys from anti-HBc (+) donors should receive lamivudine prophylaxis without HBIG for at least 1 year.
In the setting of HBs Ag (+) donors, recipients with protective anti-HBs (> 10 mIU/mL) were considered suitable to receive the allocation of kidney grafts.
Further risk should be assessed by the result of the NAT test and HBV DNA measurement. If the result of nucleic acid for HBV was negative and HBV DNA was undetectable no NA prophylaxis (in the setting of no potent induction therapy), or prescription of NA alone without HBIG. If the anti-HBs is > 100 mIU/mL, one can proceed to KT without NA prophylaxis.
The first donor group is the anti-HBc positive group in which the rate of transmission appears to be negligible according to the recipient’s
protective immunity status. The overall seroconversion rate was 3.24%.
The second donor group is the HBsAg positive group where the HBV transmission remains a challenging problem.
Kidney transplant from donors with hepatitis B: A challenging
treatment option
Praopilad Srisuwarn et al
Thank you Dr Prakash for such great answer but few comments need clarification:
1- Do you think you need to check the donor for HDV as well?
2-When you quote a reference please put the complete reference not as you mentioned Praopilad Srisuwarn et al
3- The diagram you quoted is interesting where it mandated check of HDV DNA which you did not mention in details in your answer
Will you accept this DBD donor?
According to the guidelines of the British Transplantation Society, kidneys from HBsAg positive donors can be used for any recipient after assessing the risks and benefits. Therefore, considering the recipient’s urgent need for a transplant, such as poor vascular access, uremia despite hemodialysis, or poor tolerability for dialysis, accepting this DBD donor seems appropriate. However, it is important to note that this donor should not be used if the recipient is co-infected with HBV and HDV.
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
If the recipient of the liver transplant is also HBsAg positive, it is possible to accept a live donor who is HBsAg positive as well. However, certain conditions need to be met. The recipient should be prescribed antiviral medications to control HBV replication after the transplant. It is important to note that there is a high risk of HBV reactivation, so even HBsAg positive patients who did not require antivirals before the transplant should start taking antiviral medications (such as tenofovir or entecavir) at the time of the transplant and continue taking them indefinitely, regardless of HBV DNA levels.Regular monitoring of liver enzymes and HBV DNA should be conducted every 3 to 6 months, and an abdominal ultrasound should be performed every 6 months.
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management? What is the differential diagnosis? How would you manage this case?
This donor after DBD can be accepted only if there is history indicative of HBV.
However according to current guidelines accepting such kidneys from donors with positive hepatitis B surface antigen (HBsAg) is still debatable. Yet many suggest that these organs be discarded.
Provided that the recipient has positive history of vaccination or proper previous immune response this transplantation only after patient counselling, approving to administer chemoprophylaxis prior to transplantation.
Exclusion of any abnormalities of liver function test, history of liver disease, not habitant of endemic areas of HBV.
Special consideration to the fact that fulminant hepatitis B infection had been reported in a naïve recipient who received kidneys from donors with HBsAg (+)/HBeAg (+) donors
Recipient ought to accept administration long term prophylaxis with antiviral prophylaxis with tenofovir or entecavir can be given as well as checking the affordability of treatment from the insurance besides being counselled about risk of de novo infection.
Regular frequent post-transplant monitoring of Liver enzymes and HBV PCR should be done every 3 months in year 1 and during periods of heavy immunosuppression.
Multidisciplinary team including hepatologists as well as the need to consider their opinion for fibroscan prior to transplantation and exclusion of HCC or liver cirrhosis.
Other hepatotropic viruses screening should be performed.
I would not accept donors confirmed to be HBV positive. Hepatitis B e antigen (HBeAg) and hepatitis B e antibody (anti-HBe) positivity are indicative of viral replication and infectivity.
Differential diagnosis include the following:
Early stage of HBV infection or HBV and HDV co-infection or false positive HBsAg.
Further management:
Other hepatotropic viruses, liver enzymes, ultrasound screening should be performed.
Antiviral prophylaxis with tenofovir or entecavir can be given as this recipient is only HBcAb positive.
Regular frequent post-transplant monitoring of Liver enzymes, HBsAg and HBV PCR should be done every 3 months in year 1 and during periods of heavy immunosuppression.
Multidisciplinary team including hepatologists as well as the need to consider their opinion for vaccination.
Optimization of immunosuppressive regimen as well as avoidance of B and T cell depleting agents if possible.
Wil you accept this DBD donor?
the given donor is a SCD after brain death due to SAH….there is normal renal function of the donor….the donor is HbsAg positive…. other serological tests like anti HbsAb, HbcAb, HBeAg are negative…It signifies Chronic Hepatitis B infection.. There is no active infection in the donor as HbeAg is negative….As per the BTS guidelines kidneys from HBsAg positive donors can be used for any recipient after the risk benefit assessment…It is useful to accept the kidney to a recipient who is on the waiting list for a long time with vascualr access failure and in whom the life expectancy on dialysis isn short….the recipient should be counselled for the risk of acquiring the HBV infection…the risk of infection from HbsAg positive donor is higher than risk from HBcAb positive recipient…The recipient immune system should be checked for anti HBS titre and history of prior vaacination… It would be useful if the donor HBV DNA is avaialble and it is nnot available in this history… If the recipient is immune to HBV (anti HBs titre >100 IU/ml), there is no need for anti viral treatment in the recipient…but he requires regualr monitoring of HBV DNA levels 1 week, 2 weeks, 3 weeks and then monthly after transplant…If the donor HBV DNA is not known or if the recipient is not vaccinated or if the patients are not immune, recipient should receive antivirals namely tenofovir or lamivudine for 6 months with rigorous monitoring of the viral load…there are few recommendations to suggest that HBVIG to be used in addition to antivirals if the recipient are not immune when there is a HBsAG positive donor, but the use of IVIG may fear immunomodulation and graft rejection
.
will you accept this donor as a live donor if the recipient is also HbSAg positive ?
Yes HBsAg positive donor organs can be transplanted to HbsAg positive recipients.. The only condition is the the recipient should be started on anti virals soon after transplant and they should conitnue this for 6 months to 1 year as there is high risk of reactivation of HbsAg after renal transplant….irrespective of HBV DNA level the patient should be started on antivirals ..there should be monitoring of the liver function regularly after transplant
Assuming the donor is positive for HbsAg, HbeAg and HbeAb this indicated acute on chronic infection..There is high chances off disease transmission to the recipient. But as per the BTS guidelines and KDIGO guidelines, HbsAg positive donors can be transplanted irrespective of the recipient status..If the recipient is not immune to HBV before by vaccination, this patient is at highest risk of acquiring HBV and should receive antivirals and HBIG after transplant…If the recipient is in dire need for the kidney he may accept this risk rather than waiting on hemodialysis with poor life expectancy and poor vascular access…
if the recipient is positive for HbeAg, HbeAb, HbsAg it indicates that the patient has underlying acute or chronic hepatiis b with active infection…patient should be monitored for viral load, cirrhosis of liver and may have features of parenchymal damage..
● Will you accept this DBD donor?
☆ Transplanting an HBsAg-positive allograft into an HBsAg-negative recipient carries a significant risk of de novo infection .
☆ Transplantation of HBsAg-positive kidneys into HBV-naïve recipients may result in primary infection of the recipient, who may achieve long-term HBV suppression with NA antiviral drugs (entecavir and tenofovir), which prevents progression to cirrhosis and liver failure
☆ However, these patients remain at higher risk for hepatocellular carcinoma
● Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
☆ Kidney transplantation from HBsAg-positive donor kidneys may be safely allocated in HBsAg-positive recipients. All transplant recipients should undergo prophylaxis with lamivudine or, in case of failure, with adefovir or entecavir, which can confer long-term survival benefits
☆ Kidney transplantation in HBsAb-positive recipients with an anti-HBs titer of at least >10 IU/L could be performed safely with post-transplant HBV monitoring and, eventually, with the use of antivirals to prevent the risk of hepatitis B progression. In this setting, there appears to be no adverse impact on graft or patient survival.
☆ Transplantation of a non-liver solid organ from an HBsAg positive donor to a non-immune recipient will result in chronic infection of the recipient. In this setting, antivirals should be given to prevent HBV-related liver damage
● Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
☆ So this donor has fulminate infection and he will not be acceptable for donation
● What is your differential diagnosis?
Other concomitant virus hepatitis as HDV
● How would you manage this case?
☆ Evaluated recipient for full HBV serology
HBs Ag, HBs Ab, HBc Ab , HBe Ag, HBe Ab, PCR (HBV), PCR ( HCV), PCR ( HIV )
☆ Well vaccination for recipient
☆ Antiviral prophylaxis
☆ HBIG
☆ Monitoring for reactivating HBV or de novo infection
● Assume that the potential recipient is not desperate for a kidney from HsAg positive titre and also HeAg. Will still go ahead and accept this infected organ?
☆ In this situation I will go ahead after discussing the effects of this transplantation with the recipient ( the high risk of transmission the HBV and it’s morbidity ( graft failure and increased mortality
☆ In case of living donor I will treat him before transplantation
☆ Recipients with anti HBs Ab > 10 must receive antiviral prophylaxis with or without HBIG
☆ If HBs Ab < 10 he needs both antiviral prophylaxis and HBIG .
● Regarding a life donor with HsAg positive. What are the kidney diseases that could happen due to HBV infection?
** Renal vasculitis due to HBV related PAN
** MPGN
** Membranous nephropathy
** IgA nephropathy
References:
1) .Guidelines for Hepatitis B & Solid Organ Transplantation. BTS. March 2018.
2) .Massimiliano Veroux,Vincenzo Ardita, Daniela Corona, Alessia Giaquinta, Burcin Ekser, Nunziata Sinagra, Domenico Zerbo, Marco Patanè, Cecilia Gozzo, and Pierfrancesco Veroux1 .Kidney Transplantation From Donors with Hepatitis B . Med Sci Monit. 2016; 22: 1427–1434.
Q1: if the patient was remaining on the waiting list for a long time and there is not good vascular access, yes, however, should explain the situation and evaluate risks/benefits and start antiviral therapy and HBIg. complete the vaccination if low titer HBS Ab.
Q2: after the exclusion of HDV infection, the transplant could be performed but the recipient should take prophylaxis with tenofovir or entecavir until HBS DNA became negative but there is no need for HBIg.
Q3: in this situation, there is a high risk of transmission and there is a need to receive both antiviral and HBIg.
Q4: ΔΔ includes HBV and HDV co-infection or early stage of HBV.HBS infection transmission and needs antiviral prophylaxis and close monitoring and hepatologist consultation.
Q5: In this condition, recipient should know about the probability of HBS infection transmission and needs antiviral prophylaxis and close monitoring and hepatologist consultation.
1. Will you accept this deceased donor?
Deceased donor with HBsAg positive, HBs-AB negative, HBc-Ab negative, HBe-Ag and Ab were negative, HCV and HIV negative.
I won’t accept this donor as utilizing kidneys from donors with positive hepatitis B surface antigen (HBsAg) [HBsAg (+)] remains controversial, and it is generally suggested that such organs be discarded
unless the recipient has HBsAg positive or anti-HBs AB positive>10 IU/ml which indicate immunity in this condition the donor would be accepted in case of desperate need for the organ .
KT from living HBsAg (+) donors can be donated to anti-HBs (+) recipients with protection who have no abnormalities of liver function test, no history of liver disease within the previous 28 days, and who are not living in the area of possible mutation strain of HBV.
It is important to note that fulminant hepatitis B infection had been reported in a naïve recipient who received kidneys from donors with HBsAg (+)/HBeAg (+) donors
Recipient should receive long term prophylaxis with lamivudine and to be counselled about risk of de novo infection .
Will you accept this as a living donor if the recipient is also HBsAg positive? If yes what are the condition that you should met?
Yes I will accept him.
– For both donor and recipient : Liver function, AFP and imaging including fibroscan should be done to fully evaluate hepatic state and exclude cirrhosis and HCC .
-complete virology profile (HBV-DNA , HBeAG….)
– antiviral treatment should start for both of them.
– vaccination to recipient to protect against fulminant hepatitis
Assume both HeAg and HBeAb are positive. Will this change your management?
Hepatitis B e antigen (HBeAg) and hepatitis B e antibody (anti-HBe) are additional tests to identify viral replicative activity as HBeAg positivity which indicates active viral replication (i.e., usually a viral load > 10000 IU/mL).
In contrast, anti-HBe positivity indicates the presence of the non-replication phase (i.e., a viral load < 10000 IU/mL).
so donor with positive HBVeAg carries a high risk of infectivity, so he is not accepted
Management:
– full screening of virology in both donor and recipient.
-hepatologist consultation about the risk of infection transmission and future risk of HCC.
-receive either prophylaxis with vaccine and antiviral regimens.
– frequent monitoring for HBV every three months in the first year and thereafter every six months.
References
Guidelines for Hepatitis B & Solid Organ Transplantation, British Transplantation Society Guidelines, March 2018 First Edition
Praopilad Srisuwarn et al, Kidney transplant from donors with hepatitis B: A challenging treatment option. August 27, 2021 Volume 13 Issue 8
If need demands, HBsAg positive donor can be used for any recipient, after an individualised assessment of risk and benefit.
– Yes, i would accept this donor as a live donor if the recipient is also HBsAg positive.
– Antivirals should be used as long as possible to suppress HBV after transplantation. Regular monitoring of HBV DNA & SGPT. In this setting, there appears to be no adverse impact on graft or patient survival.
No change regarding management if DBD donor is positive for HBsAg, HBeAg & HBeAb. I would accept this donor though the risk of infection is high if need demands and after individualized assessment of risk & benefit.
Antivirals (entecavir or tenofovir) from the time of transplantation and regular monitoring of HBV DNA & LFT.
– Early stage of HBV infection
– HBV and HDV coinfection
– False positive HBsAg
– Counselling the recipient regarding chronic HBV infection, liver failure, graft failure, drug complication & death.
– Refer for hepatology consultation.
– HBV vaccination
– Antiviral from the time of transplantation
– Monitoring of LFT, HNV DNA
Will you accept this DBD donor?
Yes,I will accept this donor.HBsAg positive is not a contraindication to donation.
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
yes,i will accept.Presence or absence of cirrhosis and complications of portal hypertension if presenent should be noted.The presence of chronic HBV infection, including in patients with compensated cirrhosis (ie, without complications and no evidence of portal hypertension), is not a contraindication to kidney transplantation. Antiviral therapy has been shown to reduce the risk of HBV reactivation associated with the use of immunosuppressive therapy, with improvements in survival approaching that of HBsAg-negative kidney transplant recipient.By contrast, those with decompensated cirrhosis and portal hypertension may be considered for combined liver and kidney transplantation.
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
Main concern here is Hepatitis B reactivation .Hepatitis B e antigen (HBeAg) status and HBV DNA level prior to transplantation do not reliably predict the occurrence or timing of subsequent HBV reactivation.(Among HBsAg-positive patients, reactivation of HBV replication is generally defined by the appearance of HBV DNA in a patient who has had undetectable HBV DNA previously or by a >1 to 2 logarithmic (10- to 100-fold) increase in HBV DNA.) .There is High risk of reactivation when transplantation done in HbsAg Positive patient but my managment will be same whether or not he is HBeAg positive or not.Recipient will need life long antiviral in either case.Monitoring may be done more frequently .
What is your differential diagnosis?
Chronic hepatitis B
How would you manage this case?
Antiviral therapy has been shown to reduce the risk of HBV reactivation associated with the use of immunosuppressive therapy, with improvements in survival approaching that of HBsAg-negative kidney transplant recipients. Lifelong Antiviral needed.
For most kidney transplant recipients who require antiviral therapy to prevent HBV reactivation/infection, preferred antiviral regimens include entecavir and tenofovir. We typically administer Entecavir since it is not associated with kidney toxicity; dose adjustments are required for those with reduced kidney function If tenofovir is used, we generally prefer Tenofovir alfaenamide to tenofovir disoproxil because it is associated with a lower risk of kidney toxicity.Entecavir and tenofovir are preferred over mivudinela , which had previously been the mainstay of treatment, because lamivudine has been associated with a high rate of drug resistance with long-term use.
Yes, the recipient would need to use entecavir or tenofovir since the transplant.
Yes, maintaining the prophylaxis proposal and with the need for viral load control.
In this situation we would have the characterization of disease in high activity, so the transplant would not be performed.
Occult HBV infection or co-infection with HDV.
Performing HBV DNA PCR would close the diagnosis and could indicate the need for treatment.
Assume that the potential donor is not desperate for a kidney from HsAg positive and also HeAg.
Will still go ahead and accept this infected organ?
I will not accept as this highly infectious with seroconversion condition with active disease.
If recipient is enthusiastic than I will inform the pros and cones.
Will consider IVIG.
Regarding a life donor with HsAg positive. What are the kidney diseases that could happen due to HBV infection?
There is possibilities of polyarthritis nodosa, MPGN, MNG, treatment related MCD, FSGS.
References:
https://www.uptodate.com/contents/kidney-disease-associated-with-hepatitis-b-virus-infection/print?search=clinical-features-and-evalu&topicRef=102837&source.
I will accept only if the donor HBV DNA was negative by PCR , and the patient must be informed of the risk of HBV infection and the risk of graft loss.
Yes I will accept but before transplanting the viral load for both the donor and recipient should be suppressed and the recipient receives vaccines and antiviral therapy before and after transplantation.
No, this is highly infective condition.
Chronic active hepatitis
Co infection with HDV
Infections with other hepatitis viruses like A,C,and E.
Consultation for GIT specialist , antiviral for 6 months , regular monitoring of graft function and HBV PCR monthly during the first year post transplant.
Reference
BTS guidelines 2018.
As per BTS guidelines kidney of the HBsAg positive donor can be used for any recipient, after an individualised assessment of risk and benefit, with Lamivudine prophylaxis for six months after transplantation, although the risk of transmission is very low. (2C)
Lots of literature described favourable outcome of HBsAg positive kidney donated to HBV immune recipients. Chronic HBV infection was infrequent outcome in most of cases where antiviral prophylaxis used (at least for short period).
Yes, this DBD kidney is acceptable, if
– falls into standard immunological risk (HLA, X matching and DSA)
– the donor HBV DNA PCR is negative,
– the recipient agrees after proper counselling
– the recipient has been immunized against hepatitis-B (vaccinated with adequate HBsAb).
Proper counselling of the risks of HBV infection, need for antiviral prophylaxis and long-term monitoring; marginal risk of graft failure, liver failure, and mortality, should be explained.
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
Yes, HbsAg positive donor can donate kidney to HbsAg positive recipient.
In that case, donor HBV DNA has to be suppressed (undetectable with SVR) by using antivirals before transplant and recipient has to be placed on antivirals post-transplant.
The risk of reactivation and CHB is moderate to high, and needs life-long antiviral and monitoring.
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
This indicates high risk of infectivity, so donation should be deferred.
What is your differential diagnosis?
Co-infection with HDV infection
Chronic active hepatitis B infection
Acute on chronic (hepatitis A, E and C)
How would you manage this case?
Hepatologist consultation – involvement on treatment decision
The recipient should be counselled in detail about the risks
Immunization status (HBsAb >10IU/ml) should be ensured, else vaccination series be repeated.
– If the recipients antiHBs is < 10 and is receiving HBsAg +/ HBeAg + donor kidney, it carries the highest risk of seroconversion à HBIG + Antiviral has to be administered
Antivirals (entecavir or tenofovir) should be started immediately after transplant, continued for at least 1 year
Steroid should be minimized (or avoided, if possible), Tac dose to be kept minimum allowed.
Close monitoring of PCR for HBV DNA, LFTs, RFT and Tacrolimus drug level
References:
1. British Transplantation Society Guidelines: Guidelines for Hepatitis B & Solid Organ Transplantation 2018.
2. Yap DY, Tang CS, Yung S, et al. Long-term outcome of renal transplant recipients with chronic hepatitis B infection-impact of antiviral treatments. Transplantation 2010; 90:325
Dear All
Please substantiate your answer.
Reply to Prof Halawa’s questions
If the patient is not desperate, it is better to decline the donor
benefit of transplant vs waiting on dialysis for the next negative donor out ways the risk of transmission HBV infection, antiviral and its side effects, potential graft failure, morbidity and mortality.
2- What are the kidney diseases that could happen due to HBV infection?
The kidney diseases associated with HBV infection include:
most commonly: Membranous nephropathy, MPGN and polyarteritis nodosa (PAN).
Membranous glomerulonephritis
Other less common: Mesangial proliferative glomerulonephritis, IgA Nephropathy, FSGS, Minimal Change Disease and Amyloidosis.
References:
· Lai KN, Lai FM. Clinical features and the natural course of hepatitis B virus-related glomerulopathy in adults. Kidney Int Suppl 1991; 35:S40.
· Johnson RJ, Couser WG. Hepatitis B infection and renal disease: clinical, immunopathogenetic and therapeutic considerations. Kidney Int. 1990 Feb;37(2):663-76. doi: 10.1038/ki.1990.32. PMID: 1968522
· Shah AS, Amarapurkar DN. Spectrum of hepatitis B and renal involvement. Liver International 2018; 38(1): 23-32.
This kidney carries many risks as the donor is HBsAg positive, which means active infections. The recipient should know the risk of liver disease, high mortality, and graft disease risk.
if this recipient is not desperate for this kidney, i will reject the kidney.
Another approach is to treat the donor before RTX (in the case of a living donor) with sustained HBVsAg negative for six months before considering transplantation.
Need to check for AntiHBVsAb titer, especially if the donor is HBVsAg positive.
The main risk will come from the donor who is HBsAg , HBeAg and HBe Ab were positive as this type of donor means he is having chronic active hepatitis B and carry with him infected kidney to the recipient and on this situation vaccination status of the reciepent will affect out further decision regarding to immunize the recipient with HBIG adding to antiviral therapy .
Regarding a life donor with HBsAg positive. What are the kidney diseases that could happen due to HBV infection?
a) Membranous nephropathy
b) MPGN
c) Polyarteritis nodosa
d) IgA nephropathy
referrences
BTS
Will you accept this DBD donor?
Yes , but only if the donor has PCR negative and recipient agrees and has been immunized against hepatitis B i.e., either naturally or acquired and falls into standard immunological risk and counseling of the risks of infection and graft failure should be explained to the patient.
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
Yes, HbsAg positive donor can donate kidney to HbsAg positive recipient but the viral load should be suppressed with antivirals before transplant and placed on antivirals post-transplant .Also the patient should be counseled in detail about the risks of hep b related kidney diseases after transplant. However, if the recipient is HbsAg negative , then donation of HbsAg positive should not be done unless the patient he agrees to it.
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
This indicates high risk of infectivity, so donation should not be done. And donation can only be done if the recipient agrees and has been counseled about the risks related to hepatitis B infection post transplant.
What is your differential diagnosis?
Co-infection with HDV infection
Chronic active hepatitis B infection
Acute on chronic(hepatitis A,E and C)
How would you manage this case?
Gastroenterologist should be consulted and taken on board. The patient should be counseled in detail about the risks and should be vaccinated and patient should be placed on antivirals (entecavir or tenofovir alafenamide) immediately after transplant and close monitoring of PCR for HBV DNA along with other tests like LFTs, and graft function must
References:
1- British Transplantation Society Guidelines: Guidelines for Hepatitis B & Solid Organ Transplantation 2018.
2- Yap DY, Tang CS, Yung S, et al. Long-term outcome of renal transplant recipients with chronic hepatitis B infection-impact of antiviral treatments. Transplantation 2010; 90:325
A DBD donor with isolated HBsAg with other negative serological makes signifies a past infection and is not a contraindication for Transplantation.
If the recipient was HBV immune so he shall not receive antivirals or IVIG
But if not HBV immune he shall receive Antivirals and IVIG
Recipient shall be examined for liver enzymes, HBsAg and HBV PCR as well as ultrasound for at least the 1st year post-transplant.
If recipient is HBsAg positive, i shall accept this transplantation yet continue antivirals for life
If the Donor is HBeAg this means active viral replication and high risk of virus transmission. Tx may proceed if extreme urgency for tx with long term antivirals and IVIG
If recipient is HBeAg we shall exclude the possibility of liver affection and he may require both liver and kidney transplant
This kidney carries many risks as the donor is HBsAg positive, which means active infections. The recipient should know the risk of liver disease, high mortality, and graft disease risk.
if this recipient is not desperate for this kidney, i will reject the kidney.
Another approach is to treat the donor before RTX (in the case of a living donor) with sustained HBVsAg negative for six months before considering transplantation.
Need to check for AntiHBVsAb titer, especially if the donor is HBVsAg positive.
The main risk will come from the donor who is HBsAg , HBeAg and HBe Ab were positive as this type of donor means he is having chronic active hepatitis B and carry with him infected kidney to the recipient and on this situation vaccination status of the reciepent will affect out further decision regarding to immunize the recipient with HBIG adding to antiviral therapy .
Regarding a life donor with HBsAg positive. What are the kidney diseases that could happen due to HBV infection?
a) Membranous nephropathy
b) MPGN
c) Polyarteritis nodosa
d) IgA nephropathy
referrences
BTS
Assume that the potential recipient is not desperate for a kidney from HsAg positive titre and also HeAg. Will still go ahead and accept this infected organ?
in low endemic area – there is chance of getting a DBD with negative serology
in endemic are – we can accept this with RISK FOR TRANSMISSION in recipient
FOR LIVE DONOR
treatment with antiviral is given to make serology virus free and proceed with transplant
HBV associated membranous nephropathy in recipient is to be looked for
If the patient is not desperate for that offer, I prefer to decline that donor.
HBV infection is associated with the following renal diseases: include:
Commonly: Membranous nephropathy, MPGN &PAN.
Less commonly: mesangial proliferative GN, Ig AN , FSGS, MCD & amyloidosis.
References:
-Lai KN, Lai FM. Clinical features and the natural course of hepatitis B virus-related glomerulopathy in adults. Kidney Int Suppl 1991; 35:S40.
-Johnson RJ, Couser WG. Hepatitis B infection and renal disease: Clinical, immunopathogenetic and therapeutic considerations. Kidney Int. 1990 Feb;37(2):663-76.
· Will you accept this DBD donor?
Yes, provided that the recipient is immuned, accepted the low risk and will receive prophylactic anti viral treatment. This is because The risk of donor-transmitted HBV infection is lower in kidney transplant recipients compared with liver transplant recipients with similar serologic marker positivity.
· Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
If donor is HB s Ag positive, before we decide to accept we have to make sure that:
-There is no active liver disease in the donor, by checking liver function, HBV DNA, liver ultrasound, etc
-No active renal disease related to HBV infection, like membranous nephropathy, MPGN.
· How would you manage this case?
Check HBV DNA in the donor, HBs Ab in recipient.
Check HCV, HDV, HEV.
The recipient needs to receive anti viral prophylaxis, frequent monitor of liver function test, HBV DNA.
Recipient has low titer of HBs Ab <100 to consider HBV IVIG.
References:
1-World J Hepatol 2021 August 27; 13(8): 853-86
Will you accept this DBD donor?
Yes, with adequate prophylaxis using Tenofovir alafenamide (TAF) or Entecavir for twelve to eighteen months and monitoring post-transplant hepatitis B viral load.
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
Yes, would procceed for treatment using Tenofovir alafenamide (TAF) or Entecavir until negative and monitoring post-transplant hepatitis B viral load.
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
In this case we have Hepatitis B activity. I would not accept the donor.
What is your differential diagnosis?
Drugs interaction, CNI toxicity, other hepatitis infections, autoimmune diseases
How would you manage this case?
Since the donor is HBsAg positive, the recipient should be checked for
If HbsAb < 10 vaccine and immunoglobullin
If HBeAg is positive, do not proceed with transplantation
If HBV DNA positive should call a hepatologist or Infectologist to assure management
Yes ,,,
If need demands, the non-liver solid organs of the HBsAg positive organ donor can be used for any recipient, after an individualised assessment of risk and benefit. (2C)
The donation of non-liver solid organs from an HBsAg positive donor to an HBsAg positive recipient can be undertaken as long as antivirals are used to suppress HBV after transplantation. In this setting, there appears to be no adverse impact on graft or patient survival.
Transplantation of a non-liver solid organ from an HBsAg positive donor to a non-immune recipient will result in chronic infection of the recipient. In this setting, antivirals should be given to prevent HBV-related liver damage.
Yes,,,,
Without appropriate prophylactic treatment, HBV recurrence is almost universal
Recipients with evidence of past HBV infection (HBcAb positive alone) are at risk of HBV reactivation post-non-liver transplant and could be considered for prophylactic antiviral treatment; although monitoring for HBV recurrence is an equally acceptable strategy. (2B)
There is also the precedent of using HBsAg positive kidneys in patients with HBsAb immunity, showing good graft and patient survival using a combination of HBIG and lamivudine prophylaxis .
In carefully selected patients with appropriate consent, the use of HBsAg positive donor organs may be a useful strategy to further expand the donor pool.
,,, chronic active hepatitis,,,, I will not accept such donor
False positive result
Co infection with HDV
Chronic HBV
MDT including hepatologist and infectious
Recipient counseling
In first year post transplantion every three months LFT and HBV serology should be monitored
Vaccination according to HBs AB should be done
HBIG and lamivudine prophylaxis
• Individuals undergoing non-liver solid organ transplantation who are HBsAg positive must have liver disease staging and suppression of HBV DNA by either tenofovir or entecavir before transplantation if there is a standard clinical indication. (1B)
4. You were offered kidneys from a 53-year-old male DBD (donor after brain stem death) donor who suffered from SAH (grade 5) complicating cerebral aneurysm. His retrieval S Cr was 78 µmol/L. Virology was reported as follows: HBsAg positive, HBsAb negative, HBcAb negative, both HBeAg and HBeAb are negative. Both HCV and HIV are negative.
Issues/ concerns
– 53yo, male, DBD, suffered Grade 5 SAH, complicating cerebral aneurysm
– retrieval sCr 78
– virology screen – HBsAg positive, HBsAb negative, HBcAb negative, both HBeAg and HBeAb are negative, HCV negative, HIV negative
Will you accept this DBD donor? (1, 2)
– yes, I would, due to the growing demand for organ donors
– organs from donors with HBsAg positive (active HBV infection) have a high risk of transmission resulting in primary infection hence the need for prophylaxis
– the potential recipient should also be made aware of the increased risk of disease transmission since it may actually result in graft rejection and loss
– HBsAg positive donors can safely donate to: –
– organs from donors who are HBsAg positive should be avoided in naïve recipients (HBsAg negative, HBcAb negative, HBsAb negative) unless the benefit outweighs the risk of post-transplant de novo hepatitis B infection
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met? (1, 3)
– yes, I would if in dire need
– the donor would need to do HBV DNA viral load
– but the recipient would need to do HBV DNA viral load, HBcAb, HBsAb, HBeAg, liver enzymes, liver fibroscan, HDV Ab, HDV RNA, HCV Ab, HIV Ab prior
– assuming the above serologies are unremarkable, the recipient should be initiated on antiviral therapy with entecavir or tenofovir (entecavir preferably) aiming for undetectable HBV DNA level i.e., virological suppression
– the recipient will need to monitor HBV DNA viral load and liver enzymes so as to assess response to treatment
– previously, lamivudine was the primary antiviral agent for chronic HBV before and after transplant
– currently, entecavir and tenofovir are preferred/ superior to lamivudine since they have a high genetic barrier to resistance and as such have very low resistance rates
– entecavir and tenofovir are highly potent nucleos(t)ide analogs which are safe and effective and are given once daily orally
– however, if we have elevated HBV DNA levels, positive HBeAg, negative HBsAb: avoid transplantation due to the high risk involved
– if the recipient has features of liver cirrhosis consider a liver and kidney transplant
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management? (1)
– in this case, the priority is to treat the active infection since this is a highly infectious patient
– check HBV DNA levels, HBsAb, HBcAb IgM IgG
– offer antiviral therapy, HBIG can be considered if there is no response to treatment with antiviral therapy
– once virologically suppressed then we can consider donation
– HBeAg and HBeAb tests are used to identify viral replicative activity
– a positive HBeAg indicates active viral replication usually a viral load >10,000 IU/ml
– on the other hand, a positive HBeAb indicates the presence of a non-replication phase i.e., viral load <10,000 IU/ml
– HBsAb is a marker of immune status as a result of either naturally-acquired or vaccine-acquired immunity
– NAT (nucleic acid test) for HBV, HCV and HIV – it is done to improve the sensitivity of screening tests, it has been proposed as an optional screening test among donors
What is your differential diagnosis?
– HBV reactivation
– Past infection
– False positive HBsAg
– HBV/ HDV coinfection
How would you manage this case?
– multidisciplinary approach: engage a hepatologist, infectious disease specialist
– recipient would need to do HBV DNA viral load, HBcAb, HBsAb, HBeAg, HDV Ab, HDV RNA, liver enzymes, liver fibroscan, HCV Ab, HIV Ab prior
– the patient should be initiated on antiviral therapy with entecavir or tenofovir (entecavir preferably) aiming for undetectable HBV DNA level i.e., virological suppression
– monitor HBV DNA PCR viral load to assess response to therapy
– HBIG can be considered if there is no response to antiviral therapy
References
1. Srisuwarn P, Sumethkul V. Kidney transplant from donors with hepatitis B: A challenging treatment option. World journal of hepatology. 2021 Aug 27;13(8):853-67. PubMed PMID: 34552692. Pubmed Central PMCID: PMC8422915. Epub 2021/09/24. eng.
2. Huprikar S, Danziger-Isakov L, Ahn J, Naugler S, Blumberg E, Avery RK, et al. Solid organ transplantation from hepatitis B virus-positive donors: consensus guidelines for recipient management. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2015 May;15(5):1162-72. PubMed PMID: 25707744. Epub 2015/02/25. eng.
3. Song JE, Kim DY. Diagnosis of hepatitis B. Annals of translational medicine. 2016 Sep;4(18):338. PubMed PMID: 27761442. Pubmed Central PMCID: PMC5066055. Epub 2016/10/21. eng.
Will you accept this DBD donor?
Yes.
But only if potential recipient is very desperate. Patient counselling regarding risk of HBV infection is very important. He will need immune globulins and nucleoside analogue therapy.
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
Yes
He will be at high risk for recurrence. Combinition treatment with immune globulins and nucleoside analogue therapy will be needed from transplant time . Long term prophylaxis with lamuvidine can confer survival benefits.
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management
It will be high risk case. I will check HBV DNA positivity at the time of transplant Assessment of liver functions is required. Likely chronic active phase. He should receive Hep B immune globulins and nucleoside analogue.
What is your differential diagnosis?
Occult Hepatitis B infection, HDV coinfection,
How would you manage this case?
Recipient need to be screened for HBsAg , HBeAg, HBeAb, HDV, HBV DNA levels
Discussion with Hepatologist
Counselling the patient about the risk of post transplant reactivation, Reinfection,
References
BTS Guidelines 2018
Will you accept this donor?
Yes, I will accept this case as potential donor.
According to British society of kidney transplantation this HBV donor can be accepted as potential kidney donor but special precautions including HBeAg negative PCR and HDV PCR negative.
Regarding recipient he should be vaccinated with sufficient antibodies titer at least above 10iu/ml (preferred above 100iu/ml).
Will you accept this donor as alive donor if the recipient is also HBsAg positive
No, donor should be healthy individual with low risk of developing ESRD and HBV is associated with cryoglobinemia and GN that’s why I will only accept this condition from deceased donor.
Suppose the donor is deceased and recipient also is HBsAg positive I will accept but with special precautions because the risk of reactivation
-Regarding recipient should be not of viremia at the time of transplant (PCR negative and HBeAg negative), not decompensated liver , he is already on lifelong prophylactic treatment and low immunological risk to avoid use of heavy immunosuppression induction therapy.
–Regarding donor: he should have no high viral load detected by PCR, HBeAg -ve and negative HDV Co-infection.
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
I will discard this kidney
What is your differential diagnosis?
-past infection (HBVsAg – ve and HBC antibody +ve)
-chronic state (HBVs Ag +ve and HBC antibodies +ve)
How would you manage this case?
I will do labs for bith donor and recipient including
-Donor:HDV PCR, HBVe Ag and HBV PCR
· If all positive I will reject the donor
· If all negative, I will accept the donor
· If HBV PCR positive, I will accept this graft for immune recipient with antibodies titer above 100 iu/ml or desperate non immune recipient with urgent need for transplantation (like failed vascular access) after proper counseling of the risk of transmission and post-transplant HBIg and prophylactic antiviral therapy for 1year post transplant and frequent moitoring of liver enzymes and viral load by PCR every 3 months.
· If HBVeAg or HDV PCR positive I will reject the donor.
-Reciepient: HBV antibody titer
· If below 10iu/ml: revaccinated pretransplant if possible and follow up titre 4weaks if not he may need antiviral treatment with or without HBIg based on donor viral status.
· If more than 100 IU/ml go ahead for transplant with no need for revaccination but antiviral prophylactic based on donor viral status.
References
1- Chan TM, Fang GX, Tang CS, et al. Preemptive lamivudine therapy based on HBV DNA level in HBsAg-positive kidney allograft recipients. Hepatology 2002; 36:1246.
2- Yap DY, Tang CS, Yung S, et al. Long-term outcome of renal transplant recipients with chronic hepatitis B infection-impact of antiviral treatments. Transplantation 2010; 90:325.
3- Liaw YF, Sung JJ, Chow WC, et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med 2004; 351:1521.
4- Loomba R, Rowley A, Wesley R, et al. Systematic review: the effect of preventive lamivudine on hepatitis B reactivation during chemotherapy. Ann Intern Med 2008; 148:519.
5- Han DJ, Kim TH, Park SK, et al. Results on preemptive or prophylactic treatment of lamivudine in HBsAg (+) renal allograft recipients: comparison with salvage treatment after hepatic dysfunction with HBV recurrence. Transplantation 2001; 71:387.
6- Chancharoenthana W, Townamchai N, Pongpirul K, et al. The outcomes of kidney transplantation in hepatitis B surface antigen (HBsAg)-negative recipients receiving graft from HBsAg-positive donors: a retrospective, propensity score-matched study. Am J Transplant 2014; 14:2814.
7- Shaikh SA, Kahn J, Aksentijevic A, et al. A multicenter evaluation of hepatitis B reactivation with and without antiviral prophylaxis after kidney transplantation. Transpl Infect Dis 2022; 24:e13751.
YES .
If yes, what are the conditions that should be met?
The donation of non-liver solid organs from an HBsAg positive donor to an HBsAg positive recipient can be undertaken as long as antivirals are used to suppress HBV after transplantation.
Pre-transplant suppression for patients with HBsAg positive disease should be given with tenofovir or entecavir .
Also can donate to immune-recipients with anti-HBs at least 10 mIU/mL is a key factor in overcoming the risk of HBV transmission.
Yes ,this high infectious risk donors better to be avoided.
Acute or chronic HBV infection.
Blood tests for HBV DNA, HBe Ag, HBe AB and liver function tests should be routinely
monitored after transplantation and when there is a change of immunosuppression.
accordingly HB virus drugs can be given.
References:
1-Guidelines for Hepatitis B & Solid Organ Transplantation. BTS 2018.
Will you accept this donor?
-No , I will not accept him except in emergenct situations as recipient running out of vascular access.
This donor with HBsAg positive, negative ( HBsAb, HBcAb, HbeAg and HBe Ab) mostly has acute HBV infection and still in window phase and has high risk for HBV transmission ,so further risk assessment is needed including risk of HBV infection as previous blood transfusion , liver function status and HBV DNA PCR.
– Will you accept this donor if living donor and recipient is also HBsAg positive?
Yes , I will and start prophylactic treatment immediately after transplantation.
– If yes what conditions should be met?
I would prefer to give this graft toelderly recipient with no other hepatic risk factors as no fatty liver and normal liver function tests , in addition , low immunological risk so no need for heavy IS protocol .
.
Ø Yes accepted for donation after HBV DNA
Ø HBsAg positive donor to an HBsAg positive recipient can be undertaken as long as antivirals are used to suppress HBV after transplantation.
Ø The HBsAg positive organ donor can be used for any recipient, after an individualized assessment of risk and benefit
Ø The HBV DNA viral load at the time of transplantation is a key determinant in the risk of HBV recurrence
HBeAg and HBeAb are positive in addition to positive HBsAg this indicate chronic hepatitis treated with anti vral therapy entecavir
HBsAG -+VE
HBeAG NEG
HBsAB NEG
HBcAB NEG
HBeAB NEG
Acceptance of deceased donor;
Acceptance of living donor if recipient is also HBsAG +VE and the recommendations to be met;
Both HBeAG and HBeAB + VE, will this mgt change?
DDX;
MGT.
REF;
I will accept infected kidney if recipient is desperate but should be counselling regarding transmission of disease and risk of rejection and loss graft.
Yes I will accept this case for transplant but should do HBV DNA viral load and HbsAb and should receive anti viral therapy with monitoring of HBV DNA
It’s means highly infected hepatitis B , should be treated first with anti viral therapy and receive HB immunoglobulin
Reactivated HBV
Past infection
Serial monitoring of HBV DNA PCR and HbsAB
Start Antiviral therapy tenofovir and entecavir
👉 HBV SAg postive means active infection so HBV PCR is essential, and only used for HBV postive recipient after high risk consent , counseling about risk of activation and treatment with antiviral therapy , tenofovir is indicated
👉 we can accept. But with PCR follow up and commencing antiviral therapy.
👉 In case of postive HB eAg and antibodies, indicating active infection with high viral replication (corresponding mainly to high PCR viral titer ), it is CI to accept the donation offer.
👉 Differential diagnosis is either early acute infection or chronic HBV infection.
👉 use the offer with prophylactic vaccination or immunization until Ig reaches protective level and starting anti viral therapy with close monitoring of HBV PCR.
Will you accept this DBD donor?
No, not at all.
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
Yes, in following conditions
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
This is chronic HBV infection with persisting replicating virus. I will not accept this person as donor
What is your differential diagnosis?
Recovering infection if anti HBs is also positive
Regarding a life donor with HsAg positive. What are the kidney diseases that could happen due to HBV infection?
Membranous nephropathy
MPGN
IgA Nephropathy
REF
BTS GUIDELINES
Depeding on the BTS recommendation
The use of HBsAg positive donor organs may be a useful strategy to further expand the donor pool.
The donation of non-liver solid organs from an HBsAg positive donor to an HBsAg positive recipient can be undertaken as long as antivirals are used to suppress HBV after transplantation.
There is a significant published literature describing the outcome of HBsAg positive kidney donation to HBV immune recipients
Therefore in this setting we should evaluate the immune status of the recipient
In the majority of cases, antiviral prophylaxis has been given after transplantation.
Yes if the condition of the recipient is urgent for transplant. We can ,recently and depending on some expertise, go toward renal transplantation. However, HBIG and antiviral should be started. The close monitoring serology and HBV DNA should be performed routinely
It is preferable not to accept this patient
However, if we can’t delay renal transplantation, in this case we should perform HBV DNA for the donor
And
HBsAB for the recipient to evaluate the immune state in addition to HBsAg
A- If the recipient has HBsAb
antivirals are stopped after a period of prophylaxis, the recipient should receive long-term monitoring for the appearance of HBsAg.
B- if it is a non-immune recipient this will result in chronic infection of the recipient. In this setting, antivirals should be given to prevent HBV-related liver damage
A- THIS positivity indicates the activity of desease.
Then it is preferable to perform HBV DNA and
Stop renal transplantation
B- If it is the case of living donation
treatment should be started before transplant.
– Early HBV infection
– HDV co-infection with HBV
– False positive HBsAg results
We should inform the patient about the risk of this transplantation
We should indicate the level of risk depending
1- if the recipient has HBsAg pos or neg
2- if the recipient has HBsAb pos or neg
If the recipient had HBsAg neg or if the patient has HBsAg pos with no immune state (HBsAb neg) ==> high risk==> HBIG + antiviral
if the patient has HBsAg pos with immune state (HBsAb pos) ==> less risk==> prophylaxis antiviral
1- we have to assess the donor for HBV RNA, liver enzymes and imaging of the liver
2- if live donor and the recipient is HBs Ag positive:
3- both HBeAg and HBeAb are positive indicate viral replication —- I will not accept
4- DD:
5- Management
combination therapy with HBIg and/or a potent nucleotides analogue (NA) is
recommended from the time of transplantation to prevent HBV reinfection post-
liver transplant.
Will you accept this DBD donor?
A positive HBsAg test indicates active infection and HBV carefully selected patients with
appropriate consent, the use of HBsAg-positive donor organs may be a useful strategy to
further, expand the donor pool as it could be transmitted by any organ or tissue in this setting. HBsAg-positive donors can be considered for HBsAg-positive recipients, or in exceptional
circumstances after specialist advice, informed consent, or for HBcAb-positive
recipients which Indicate a low risk of reactivation Most guidelines exclude them from donation unless the recipient is also HBs Ag positive in urgent cases.
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
He is at high risk of recurrence,
combination therapy with HBIg and/or a potent NA is recommended from the time
of transplantation to prevent HBV reinfection post-liver transplant. (1B)
so, the answer is Yes, provide the HBV DNA < 200 and rule out HDV co-infection in the recipient with the use of a combination of HBIG and lamivudine prophylaxis.
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
Need to check the HBV DNA if positive at the time of transplant,
Any evidence of HDV co-infection by HDV antibodies serology and if positive HDV serology e need to do HDV RNA testing must be performed in potential transplant recipients where HDV
serology is positive or equivocal. (1B).
What is your differential diagnosis?
occult HBV or HDV co-infection also another viral screen like HIV and HCV screen
How would you manage this case?
As the donor HBsAg positive need to screen the recipient with HBs Ag, HBe Ag, and AB, HDV serology, and HBV DNA level and refer to a hepatologist as part of the MDT approach with proper counseling for the recipient about the risk of Post transplantation re-infection or reactivation or eve denovo HBV infection including the risk of HBV related de nonvo nephropathies like MGN or MPGN.
Reference
1. BTS guideline 2018.
I will not accept this donor as neither DBD nor living donor because it is high risk and associated with higher mortality……
waiting more better than treatment of complications
Thanks, Delshad
This is a short answer. Justify it, please!
53- year DBD, HBsAg positive, HBsAB negative, HB cAb negative, HBeAg and Ab were negative, HCV and HIV negative.
1. Will you accept this deceased donor?
· Yes if the recipient is having HBsAg positive as well
If the recipient is having natural or acquired immunity (anti-HBs concentration of >10 IU/ml)
· In both conditions the recipient should receive long term prophylaxis with lamivudine or, in case of failure, with adefovir or entecavir.
· In HBV naïve recipient the risk is high, it depends on the organ demand, but still can go for transplantation.
2. Will you accept this as a living donor if the recipient is also HBsAg positive? If yes what are the condition that you should met?
Yes
· Referred to see a hepatologist to asses HepBV DNA, liver function, fibroscan/ liver biopsy, give antiviral treatment and exclude HCC.
· This patients should receive long term prophylaxis with lamivudine, with adefovir or entecavir, as this can confer long-term survival benefits.
3. Assume both HeAg and HBeAb are positive. Will this change your management?
· The acceptance of donors with HBV infection depends on risk assessment of HBV infectivity risk.
· Since this donor with HBVeAg carries a high risk of infectivity and fulminant hepatitis B infection, this donor should not be used.
Management:
· Since the donor is HBsAg positive, the recipient should be checked for HBs Ag and antibodies, HBVeAg and antibodies, and HBV DNA level and be assessed by a hepatologist if any abnormal results
· Then according to risk, the recipient should receive either prophylaxis with vaccine, HBIG, and antiviral regimens.
· Monitoring for HBV Recurrence or De Novo Infection: HBV DNA and HBsAg should be monitored every three months in the first year and thereafter every six months.
References
1. Guidelines for Hepatitis B & Solid Organ Transplantation, British Transplantation Society Guidelines, March 2018 First Edition
2. Huprikar1, et al, Solid Organ Transplantation From Hepatitis B Virus–Positive Donors: Consensus Guidelines for Recipient Management, American Journal of Transplantation 2015; 15: 1162–1172
3. Praopilad Srisuwarn et al, Kidney transplant from donors with hepatitis B: A challenging treatment option. August 27, 2021 Volume 13 Issue 8
Thanks, Mannoli
I agree with you.
Will you accept this DBD donor?
Yeas I will accept ,after informed the recipient about the disease and possibility of transmission and reactivation and what is role of immune supressions.
Management
First assessment of immune status of the recipient
CBC ,RFT ,LFT ,LIVER ENZYMES , HBsAg , HBsAb , HBeAg , HBeAb , HBcAb , HBV DNA ,
Investigate for co infection HDV infection.
If recipient immune and vaccinated we proceed to transplant, HBV immunoglobulin and anti viral should be started.
Monitor the recurrence with :
HBV DNA positive at time of transplant.
HBeAg positive patients.
Those transplanted for hepatocellular carcinoma.
HIV co-infected.
If recipient had no history of prior infection and not immune when donor has HBsAg positive ,the transplantation is complicated and not advice.
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
After assessment of serum ALT, HBV DNA, is it active disease and HBV DNA is high that need treatment with anti viral till HBV DNA is getting low then answer is yeas and will accept, In addition, hepatitis flare was defined by rising of serum ALT more than 3 times the baseline level and > 100 U/L with evidence of hepatitis B reactivation monitoring liver enzymes, HBsAg, and HBV DNA every 3 mo for at least 12 mo post-transplantation. Subsequent management was based on the evolution of test results over the first year.
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
No change , In patient positive HBsAg ,positive HBeAg, positive HBeAb we need to do ALT , AST to asses the active disease which need urgent treatment with antiviral for live donor to decrease the infection and lowering the transmission ,and also assessing the immune status of the recipient, if vaccinated and immune well we proceed . The transplant recipient should receive Hepatitis B Immunoglobulin (HBIG) with antivirals (Tenofovir/ entecavir) as prophylactic treatment for HBV, especially non-protective anti-HBsAb titres and if the HBV DNA status of the donor is not known.
What is your differential diagnosis?
Acute viral hepatitis
Acute on chronic HBV infection
Reactivation of chronic hepatitis B
References
1. BTS Guidelines for Hepatitis B & Solid Organ Transplantation, 2018
2 . Wachs ME, Amend WJ, Ascher NL, Bretan PN, Emond J, Lake JR, Melzer JS, Roberts JP, Tomlanovich SJ, Vincenti F. The risk of transmission of hepatitis B from HBsAg(-), HBcAb(+), HBIgM(-) organ donors. Transplantation. 1995;59:230–234. [PubMed] [Google Scholar]
3 . Schieck A, Schulze A, Gähler C, Müller T, Haberkorn U, Alexandrov A, Urban S, Mier W. Hepatitis B virus hepatotropism is mediated by specific receptor recognition in the liver and not restricted to susceptible hosts. Hepatology. 2013;58:43–53. [PubMed] [Google Scholar
Even with Hep Be Ag positivity, would you accept this donor?
HBeAg positive is one of the marker of acute infection and associated with high HBVDNA we need to treat first to lowering HBVDNA then proceed.
Will you accept this DBD donor?
Normally a deceased donor who is HBsAg positive will not be accepted. However, if there is a potential recipient who has been fully vaccinated against hepatitis B and has acceptable titers of the HBsAb and has exhausted his access sites, may be considered to get the kidney after counseling and explaining the risks
Living donor:
if this was a live donor who is HbsAg positive and the recipient is also HBsAg positive, then the transplant can proceed after meeting the following criteria:
The recipient should get antiviral prophylaxis and the liver enzymes as well as the hepatitis B viral load should be monitored
If both HBeAg and HBeAb are positive in addition to HBsAg:
Hepatitis B e Ag is a secretory protein that is processed from the precode protein. It is an early antigen and not an envelope antigen. The presence of HBeAg is usually associated with high levels of HBV DNA and higher rates of transmission.
HBeAg to HBeAb seroconversion occurs early in patients with acute infection, prior to HBsAg to HBsAb conversion. So the presence of all three being positive could suggest that it is an acute infection and the transplant will have to be postponed to asses for HbsAg seroconversion to HBsA. So one would need to do the HBcAb. If the IgM is positive it would signify an acute infection and the transplant would need to be postponed
I appreciate your clinical approach. I wish you could support your argument by evidence
Dear All
Please substantiate your answer.
Assume that the potential recipient is not desperate for a kidney from HsAg positive titer and also HeAg. Will still go ahead and accept this infected organ?
At this situation, I will accept the case with the following considerations
Regarding a life donor with HsAg positive. What are the kidney diseases that could happen due to HBV infection?
References
1. Johnson RJ, Couser WG. Hepatitis B infection and renal disease: Clinical, immunopathogenetic and therapeutic considerations. Kidney Int 1990; 37:663.
2. Lai KN, Lai FM. Clinical features and the natural course of hepatitis B virus-related glomerulopathy in adults. Kidney Int Suppl 1991; 35:S40.
3. Chung DR, Yang WS, Kim SB, et al. Treatment of hepatitis B virus associated glomerulonephritis with recombinant human alpha interferon. Am J Nephrol 1997; 17:112.
4. Sun IO, Hong YA, Park HS, et al. Clinical characteristics and treatment of patients with IgA nephropathy and hepatitis B surface antigen. Ren Fail 2013; 35:446.
5. Zhou TB, Jiang ZP. Is there an association of hepatitis B virus infection with minimal change disease of nephrotic syndrome? A clinical observational report. Ren Fail 2015; 37:459.
6. Sakai K, Morito N, Usui J, et al. Focal segmental glomerulosclerosis as a complication of hepatitis B virus infection. Nephrol Dial Transplant 2011; 26:371.
7. Saha A, Theis JD, Vrana JA, et al. AA amyloidosis associated with hepatitis B. Nephrol Dial Transplant 2011; 26:2407
8. Takekoshi Y, Tochimaru H, Nagata Y, Itami N. Immunopathogenetic mechanisms of hepatitis B virus-related glomerulopathy. Kidney Int Suppl 1991; 35:S34.
I make note of your interpretation of reports pertaining to HBV infections. I like your summary, analysis and take home messages.
Thanks, Sherif
Therefore, we need to exclude an HBV-induced kidney disease in the donor.
Will you transplant this infected kidney to a CKD patient who is not desperate for a transplant?
I would not myself.
Definitely no, as there is increased risk for hepatitis, liver faliure, graft and patient loss
If the potential recipient is not desperate to receive a kidney, then the kidneys should not be transplanted
The kidney diseases that could happen due to HBV infection include:
Short and sweet.I appreciate your clinical approach. I wish you could support your argument by evidence
Can mesangio-proliferative GN also happen due to HBV?
Thank you Professor Sharma
Yes. Hepatitis B can cause mesangioproliferative GN
Q1. In case the recipient is not desperate, then there is no urgent demand and the best for us is to wait for a better kidney for a HBsAg negative recipient.
Q2. Kidney disease due to HBV:
Source, BTS guideline 2018, Oxiford nephrology handbook 2th edition
I appreciate your clinical approach. I wish you could support your argument by evidence
Thnx prof,
BTS, guideline 2018
1- Assume that the potential recipient is not desperate for a kidney from HsAg positive titre and also HeAg. Will still go ahead and accept this infected organ?
If the recipient is not desperate on the HBsAg/HBeAg +ve ( high risk for reactivation), i will not proceed transplanting the infected organ to the patient.
2- Regarding a life donor with HsAg positive. What are the kidney diseases that could happen due to HBV infection?
he diseases could happen due to hepatitis B infection form a donor HBsAg +ve are:
References:
(1) Huprikar S, Danziger-Isakov L, Ahn J, Naugler S, Blumberg E, Avery RK, Koval C, Lease ED, Pillai A, Doucette KE, Levitsky J, Morris MI, Lu K, McDermott JK, Mone T, Orlowski JP, Dadhania DM, Abbott K, Horslen S, Laskin BL, Mougdil A, Venkat VL, Korenblat K, Kumar V, Grossi P, Bloom RD, Brown K, Kotton CN, Kumar D. Solid organ transplantation from hepatitis B virus-positive donors: consensus guidelines for recipient management. Am J Transplant. 2015 May;15(5):1162-72. doi: 10.1111/ajt.13187. Epub 2015 Feb 23. PMID: 25707744.
(2) UpToDate –Kidney transplantation in adults: Hepatitis B virus infection in kidney transplant recipients
I appreciate your clinical approach.
If patient is not desperate and no urgency for transplantation, it is better to decline the donor.
The kidney diseases associated with HBV infection include:
Most commonly: Membranous nephropathy, MPGN and polyarteritis nodosa (PAN).
Other less common: mesangial proliferative glomerulonephritis, IgAN , FSGS, MCD and amyloidosis.
References:
-Lai KN, Lai FM. Clinical features and the natural course of hepatitis B virus-related glomerulopathy in adults. Kidney Int Suppl 1991; 35:S40.
-Johnson RJ, Couser WG. Hepatitis B infection and renal disease: clinical, immunopathogenetic and therapeutic considerations. Kidney Int. 1990 Feb;37(2):663-76. doi: 10.1038/ki.1990.32. PMID: 1968522.
I like your list.
1: I will not accept a kidney from a donor with active viral HBV in replication.
As long as there is no emergency, the risk-benefit is that I will not expose the recipient to this high risk of transmission of infection.
2- What are the kidney diseases that could happen due to HBV infection?
Renal diseases resulting from HBV infection are membranous glomerulonephritis, membranoproliferative glomerulonephritis (MPGN), Polyarteritis nodosa (PAN), mesangial proliferative glomerulonephritis, IgA nephropathy, and amyloidosis.
Shah, A. S., & Amarapurkar, D. N. (2018). Spectrum of hepatitis B and renal involvement. Liver International, 38(1), 23-32.
References:
Eckardt, K. U., Kasiske, B. L., & Zeier, M. G. (2009). KDIGO clinical practice guideline for the care of kidney transplant recipients. American Journal of Transplantation, 9, S1-S155.
I appreciate your clinical approach.
No;
-If recipient is not desperate for kidney from doner who is HBsAg positive and also HBe Ag (high risk for infection), and without informed consent for acceptance the risk for HBV infection and for acceptance for life-long combination therapy with HBIG and a potent NA can potentially be given to this patient.
-So as no urgency, I will not accept this infected organ and I will ask recipient to sign refusal form and keep him on waiting list for cadaveric KTx.
Kidney diseases that could happen due to HBV infection:
-Infection with hepatitis B virus (HBV) may be associated with a variety of kidney diseases.
-The three most common types of kidney disease resulting from HBV infection are:
●Membranous nephropathy
●Membranoproliferative glomerulonephritis (MPGN)
●Polyarteritis nodosa (PAN)
-In addition, HBV infection has been associated with mesangial proliferative glomerulonephritis, immunoglobulin A (IgA) nephropathy, crescentic glomerulonephritis, focal segmental glomerulosclerosis (FSGS), minimal change disease, and amyloidosis, although the causative role of HBV has been debated for some of these conditions.
-Rapidly progressive glomerulonephritis (RPGN); In rare patients with RPGN with extensive crescentic disease, presumed to be due to HBV infection.
References;
-Johnson RJ , Couser WG. Hepatitis B infection and renal disease:Clinical, immunopathogenetic and therapeutic coniderations. Kidney Int 1990;37:663.
-Lai KN, Lai FM. Clinical features and the natural course of hepatitis B virus-related glomerulopathy in adults. Kidney Int Suppl 1991;35:S40.
-Kupin WL. Viral-Associated GN:Hepatitis B and Other Viral Infections. Clin J Am Soc Nephrol 2017; 12:1529 .
I appreciate your clinical approach well supported by evidence
No , I will not accept this donor if the recipient was not desperate as there is ariskof HBV transmission to the recipient , this must be explained clearly to the recipient.
2- Kidney diseases caused by HBV
a- Membranous glomerulopathy.
b-Mesangioproliferative GN with or with out cryoglubulinemia.
c-Polyarteritis nodosa.
d- less common IgA nephropathy.
I appreciate your clinical approach. I wish you could support your argument by evidence
1. Assume that the potential recipient is not desperate for a kidney from HBsAg positive titre and also HBeAg. Will still go ahead and accept this infected organ?
In case the prospective recipient is not willing for such a donor, the transplant should not be proceeded with. But the patient needs to be counselled regarding the status/ risks and benefits of transplantation with respect to such a donor before taking a decision.
Positive HBsAg signifies past HBV infection. Positive HBeAg and HBeAb signify HBeAg positive chronic hepatitis with active viral replication. Such patients have high HBV DNA levels usually with liver damage, and progression to cirrhosis is possible (1).
As per the British Transplantation Society guidelines, kidneys from HBsAg positive donors can be used for any recipient, after risk and benefit assessment (1).
If the donor is positive for HBsAg, HBeAg and HBeAb, I will discuss in detail with the patient regarding this DBD donor, and only if the recipient has urgent need of transplant (poor vascular access, uremia despite adequate hemodialysis, poor tolerability for dialysis), would go ahead with transplant after counselling and consent (2).
The transplant recipient should receive Hepatitis B Immunoglobulin (HBIG) with antivirals (Tenofovir/ entecavir) as prophylactic treatment for HBV, especially non-protective anti-HBsAb titres and if the HBV DNA status of the donor is not known (1-3). If the recipient is HBV immune (Anti HBsAb >10mU/ml), post-transplant antivirals need not be given, but the patient should be monitored closely and antivirals should be given on appearance of HBsAg. Patient should be monitored with liver enzymes, HBsAg and HBV DNA once in 3 months for at least 1 year post-transplant, and subsequently as per the test reports (1,3).
2. Regarding a life donor with HBsAg positive. What are the kidney diseases that could happen due to HBV infection?
The renal disease which can be seen with chronic HBV infection include (4-6):
a) Membranous nephropathy
b) MPGN
c) Polyarteritis nodosa
d) IgA nephropathy
References:
Thanks, All
If you will accept a kidney from HBV, HCV and HIV patients, remember to make sure there is no associated nephritis.
No I will not proceed the renal transplant
What are the kidney diseases that could happen due to HBV infection?
1—Membranous nephropathy —
A- secondary membranous nephropathy,
B- Compared with patients who have idiopathic or primary membranous nephropathy, patients with HBV-associated membranous nephropathy are more likely to have microscopic hematuria and lower complement levels
C- The histologic presence of mesangial cell proliferation or mesangial or subendothelial immune deposits, in addition to the typical subepithelial localization, may be a clue to suggest secondary rather than primary membranous nephropathy.
D- low prevalence of anti-PLA2R antibodies and/or PLA2R staining of the immune deposits
2– Membranoproliferative glomerulonephritis (MPGN)
Compared with hepatitis C infection, HBV infection is a rare cause of mixed cryoglobulinemia, which can be associated with MPGN
3– Polyarteritis nodosa (PAN)
HBV-associated PAN typically occurs within four months after the onset of HBV infection.
The presence of HBV-associated disease is suggested by the findings of HBsAg, HBeAg, and HBV DNA (an indicator of viral replication) in the serum
REFERENCES
Kidney disease associated with hepatitis B virus infection (UpToDate)
⭐ I think it is not wise to accept graft from HBsAg postive donor, with higher risk of disease transmission and consequently liver cell failure and higher mortality (once starting immunosupressives therapy).
👉 HBV infection is associated with membranous nephropathy , mesangioproliferative GN, MPGN and cryoglobulinemia.
No i will not accept this donor
Condition associated with hepatitis B is Poly arteries nodsum , cryoglobulinemia and membranous nephropathy and membranoproliferative glomerulonephritis
1- I will not accept this infected organ
2- HBV- related renal disease:
glomerulonephritis, membranous nephropathy, MPGN , Ig A nephropathy, mesangio-proliferative GN
References:
1- Zhang Y, Zhou JH, Yin XL, Wang FY. Treatment of hepatitis B virus-associated glomerulonephritis: a meta-analysis. World journal of gastroenterology: WJG. 2010 Feb 2;16(6):770.
Even with HBsAg positive donor/HBsAg -ve recipients, excellent Ktx can be done.
(Wang XD, Liu JP, Song TR, Huang ZL, Fan Y, Shi YY, Chen LY, Lv YH, Xu ZL, Li XH, Wang L, Lin T. Kidney Transplantation From Hepatitis B Surface Antigen (HBsAg)-Positive Living Donors to HBsAg-Negative Recipients: Clinical Outcomes at a High-Volume Center in China. Clin Infect Dis. 2021 Mar 15;72(6):1016-1023. doi: 10.1093/cid/ciaa178. PMID: 32100025.). So I prefer to go ahead with transplantation after discussing this with potential recipients. Regarding the donor, as he is anti-HeV negative (carrier), I will also check HBV DNA.
No , I will not accept this donor if the recipient was not desperate as there is ariskof HBV transmission to the recipient , this must be explained clearly to the recipient.
1- Kidney diseases caused by HBV
a- Membranous glomerulopathy.
b-Mesangioproliferative GN with or with out cryoglubulinemia.
c-Polyarteritis nodosa.
d- less common IgA nephropathy.
Assume that the potential recipient is not desperate for a kidney from HsAg positive titre and also HeAg. Will still go ahead and accept this infected organ?
No ,its high risk of infection ,specially HBV DNA positive and no desperate need or no
HBVS ag positive recipient .
What are the kidney diseases that could happen due to HBV infection?
membranous nephropathy
●
Membranoproliferative glomerulonephritis (MPGN)
●
Polyarteritis nodosa (PAN)
Better not to transplant if potential recipient is not desperate
Diseases due HBV infection include, Membranous nephropathy, Polyarteritis Nodosa -PAN MPGN
1-I will not proceed to transplant the recipient with the patient with hepatitis BsAg positive as the risk of hepatitis, hepatic failure, graft loss, and even death.
2- most common glommularnephritis caused by hepatitis B virus are membranous nephropathy and MPGN
others such as amyloidosis, IgA nephropathy, FSGS MCD
Assume that the potential recipient is not desperate for a kidney from HsAg positive titre and also HBeAg. Will you still go ahead and accept this infected organ?
– no, I would not since there is a high-risk for HBV transmission
Regarding a live donor with HBsAg positive. What are the kidney diseases that could happen due to HBV infection? (1-3)
– Membranous nephropathy
– MPGN (membranoproliferative glomerulonephritis)
– Polyarteritis nodosa (PAN)
– Mesangioproliferative glomerulonephritis
– IgA nephropathy
– Crescentic glomerulonephritis
– FSGS (focal segmental glomerulosclerosis)
– Minimal change disease
– Amyloidosis
Please substantiate your answer.
References
1. Johnson RJ, Couser WG. Hepatitis B infection and renal disease: clinical, immunopathogenetic and therapeutic considerations. Kidney Int. 1990 Feb;37(2):663-76. PubMed PMID: 1968522. Epub 1990/02/01. eng.
2. Lai KN, Lai FM. Clinical features and the natural course of hepatitis B virus-related glomerulopathy in adults. Kidney international Supplement. 1991 Dec;35:S40-5. PubMed PMID: 1770709. Epub 1991/12/01. eng.
3. Kupin WL. Viral-Associated GN: Hepatitis B and Other Viral Infections. Clinical journal of the American Society of Nephrology : CJASN. 2017 Sep 7;12(9):1529-33. PubMed PMID: 27797900. Pubmed Central PMCID: PMC5586580. Epub 2016/11/01. eng.
Assume that the potential recipient is not desperate for a kidney from HsAg positive titre and also HBeAg. Will you still go ahead and accept this infected organ?
– no, I would not since there is a high-risk for HBV transmission
Regarding a live donor with HBsAg positive. What are the kidney diseases that could happen due to HBV infection? (1-3)
– Membranous nephropathy
– MPGN (membranoproliferative glomerulonephritis)
– Polyarteritis nodosa (PAN)
– Mesangioproliferative glomerulonephritis
– IgA nephropathy
– Crescentic glomerulonephritis
– FSGS (focal segmental glomerulosclerosis)
– Minimal change disease
– Amyloidosis
Please substantiate your answer.
References
1. Johnson RJ, Couser WG. Hepatitis B infection and renal disease: clinical, immunopathogenetic and therapeutic considerations. Kidney Int. 1990 Feb;37(2):663-76. PubMed PMID: 1968522. Epub 1990/02/01. eng.
2. Lai KN, Lai FM. Clinical features and the natural course of hepatitis B virus-related glomerulopathy in adults. Kidney international Supplement. 1991 Dec;35:S40-5. PubMed PMID: 1770709. Epub 1991/12/01. eng.
3. Kupin WL. Viral-Associated GN: Hepatitis B and Other Viral Infections. Clinical journal of the American Society of Nephrology : CJASN. 2017 Sep 7;12(9):1529-33. PubMed PMID: 27797900. Pubmed Central PMCID: PMC5586580. Epub 2016/11/01. eng.
No ,I will not transplant,I would prefer a HBsAg neg organ.
HBV Renal dx;
REF;
-BTS Guidelines 2018.
Assume that the potential recipient is not desperate for a kidney from HsAg positive titre and also HeAg. Will still go ahead and accept this infected organ?
No ,its high risk of infection ,specially HBV DNA positive and no desperate need or no
HBVS ag positive recipient .
What are the kidney diseases that could happen due to HBV infection?
membranous nephropathy
●
Membranoproliferative glomerulonephritis (MPGN)
●
Polyarteritis nodosa (PAN)
Thank you Prof.
Assume that the potential recipient is not desperate for a kidney from HsAg positive titre and also HeAg. Will still go ahead and accept this infected organ?
Only if need demands and potential donor agree to receive this donor kidney after counselling regarding future risk, i wiil go ahead and accept this infected organ. (Actually after individualized assessment of risk and benefit)
Regarding a life donor with HsAg positive. What are the kidney diseases that could happen due to HBV infection?
1. Glomerulonehritis : Membranous GN, MPGN, Me proliferative GN, MCD, FSGS
2. PAN
if the patient is not desperate. There is no emergent situation and can wait for a better donor.
Associated HBV infection kidney involvements are: membranaceous nephropathy, MPGN, and polyarteritis nodosa (more common)
Less common: mesangioproliferative GN, IgA nephropathy, FSGS, and amyloidosis.
Reference:
Kidney disease associated with hepatitis B infection in UPtoDate 2023.
Will you accept this donor?
Donor with HBsAg positive, negative HBsAb, HBcAb, HbeAg and HBeAb.
Yes I would accept this donor however the recipient should be informed about the risk of de-novo infection.
Will you accept this donor if LDD and recipient is also HBsAg positive?
If yes what conditions should be met?
Yes I would accept this donor.
Additional conditions;
Recipient HBV DNA should be undetectable.
In case of high viral load recipient should be on entecarvir/ tenofovir alafenamide to reduce before transplantation.
HDV DNA and anti-HDV should be done due to risk of HDV super infection.
Assume HBeAg and HBeAb are positive
HBeAg indicates viral replication and presence of HBeAb indicates this is a chronic infection.
No, it would not not change my management.
I would still accept the donor and give lamivudine prophylaxis post-transplant.
What is your differential diagnosis?
HBsAg positive is the serological marker of HBV infection.
Hence this can occur in acute infection and if it persists for more than 6 months will indicate chronic infection.
This donor also has HBeAg is negative could indicate HBeAg negative chronic infection.
This donor with HbsAg positive could also have co-infection with HDV.
How would you manage this case?
DBD with HBsAg positive in both donor and recipient.
HBsAg positive with negative antibodies.
Requires NAAT for HBV and HDV.
Liver aminotransferase levels- ALT and AST should be done to rule out hepatitis.
Imaging of the liver- Abdominal U/S for any features of cirrhosis.
Antivirals- entecarvir/ Tenofovir alafenamide should be given life long due to risk of reactivation due to IS therapy.
References
Diagnosis of hepatitis B Jeong Eun Song, Do Young Kim
Guidelines for Hepatitis B & Solid Organ Transplantation First Edition March 2018
Solid Organ Transplantation From Hepatitis B Virus–Positive Donors: Consensus Guidelines for Recipient Management
I appreciate your clinical approach. I wish you could support your argument by evidence
Will you accept this DBD donor?
===========================
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
Conditions to be met include:
===========================
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
===========================
What is your differential diagnosis?
HBe Antigen Negative Chronic Infection (previously “inactive phase”):
HBe Antigen Negative Chronic Hepatitis (previously “immune escape phase”):
===========================
How would you manage this case?
References
I appreciate your clinical approach. I wish you could support your argument by evidence
Donor virology – HBsAg positive, HBsAb negative, HBcAb negative, both HBeAg and HBeAb negative. Both HCV and HIV are negative.
Positive HBsAg indicates current infection and that the person can infect other people. HBsAg is the antigen used to make hepatitis B vaccine.
HBsAb indicates recovery and immunity from hepatitis B viral infection. However, this donor is HBsAb negative.
HBcAb appears at the onset of symptoms in acute hepatitis B infection and persists for life. It indicates previous or ongoing infection with hepatitis B. T his donor is HBcAb negative.
1.DBD donor
Because of the scarcity of donors, I would accept this donor. However, I would inform the recipient about the risk of infection being transferred from the donor. I would allow the recipient to decide whether he/she prefers taking the risk or going back on the transplant waiting list, given that no other donors are available at present.
Recipient needs to be vaccinated. Antiviral prophylaxis is very important in this case and will be given for 6 months post transplant. HBsAg and HBsAb monitoring is crucial, and patient may need second series of vaccination depending on levels of HBsAb being less than 100 units/ml.
British Transplantation Society guidelines recommend using HBsAg positive donor for any recipient in the case of urgent transplant requirement, provided the transplant team does risk assessment and finds appropriate to proceed for transplant. This is the 2018 guideline recommendation.
2.Live donor, recipient HBsAg positive
I would accept this donor, with some amount of risk assessment in the form of the following tests :
3.Positive HBeAg, HBeAb and HBsAg
Positive HBsAg along with HBeAg indicates current infection. Positive HBeAb in this setting indicates that the infection has been chronic.
Fulminant HBV infection can occur in naive recipient when they are transplanted with HBsAg positive and HBeAg positive donor grafts. Antiviral medication regimen is crucial in this case. Recipient would have to be vaccinated prior to transplant and given antiviral therapy for 6 months post transplant. Using a different donor may be recommended.
However, if the recipient also has chronic hepatitis, then donor can be accepted with antiviral therapy such as tenofovir with careful monitoring for HBV DNA, HDV and HCV co infection, and liver enzymes.
4.Differential diagnosis
5.Management
References :
Thanks, Nandita
Nice to see your contribution.
Will you accept this DBD donor?
–Yes, this donor can be accepted, informed consent about the risk of transmission. If here is no absolute contraindication.
BTS guidelines 2018: If need demands, solid organs of the HBsAg positive organ donor can be used for any recipient, after an individualized assessment of risk and benefit, especially if urgent need for KT (exhausted multiple vascular access, with ongoing uremia despite adequate hemodialysis prescription).
Recipients should be counselled and check their willingness to receive a kidney from donors with HBsAg positivity and discussed the risk of viral transmission to be balanced against continuing on waiting list
Management of this condition:
*Evaluate recipient HBV immune status;
– Check for : HBsAg, HBsAB, HBeAg, HBeAb, HBcAb, HBV DNA, HDV
– HBsAg positive donors should not be used for HBV/HDV co-infected or HCV recipients.
– All HBV naive recipients who are must be vaccinated and the response documented.
– If HBsAb are <100 IU/mL, should be vaccinated to decrease reactivation risk ,high dose accelerated vaccine schedule given and second series can be given if no documented response.
– In HBV immune recipients of an anti‐HBc‐positive non‐hepatic organ, no prophylaxis is needed.
– HBIg is not recommended in the prevention of HBV peri‐transplant in non‐hepatic recipients. However, can be used in non-immune recipients along with antiviral therapy.
– Antiviral prophylactic given for 6-12 months after transplantation.
– Monitoring with liver enzymes, HBsAg, and HBV DNA at least every 3 months for at least 12 months post‐transplant
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
Yes, can proceed with transplantation with the following consideration: no abnormalities of liver function test, no history of liver disease within the previous 28 days, and who are not living in the area of possible mutation strain of HBV
*Additional testing required;
– Including HBeAg, anti‐HBeAb, HBcAb, quantitative HBV DNA
– liver enzymes.
– Check for HDV con-infection. HCV.
– Baseline US surveillance for HCC according to standard guidelines, with or without AFP every 6 months
– Liver biopsy maybe needed to exclude
* if HBV DNA positive should be treated with appropriate antiviral therapy.
* if HDV cannot receive organ from HBsAg positive donor.
*Treatment:
– In HBsAg‐positive KTR, the risk of reactivation of HBV, in the absence of antiviral prophylaxis, ranges from 50% to 94%.
Indicated as untreated HBsAg‐positive dialysis and KTR patients have worse survival rates compared to HBsAg‐negative with rise in HBV DNA, accelerated progression to cirrhosis and occasionally fibrosing cholestatic HBV.
– HBV DNA suppression can significantly improve the survival, ideally to be started pre-transplant.
– Potent NA is recommended; tenofovir or entecavir or lamivudine.
-Tenofovir or entecavir are preferable to lamivudine; due to their potency and high barriers to resistance.
– In those with renal impairment, Entecavir (ETV) or tenofovir alafenamide (TAF) is preferred over tenofovir disoproxil fumarate (TDF).
-Therapy should be continued up to the time of transplant and indefinitely posttransplant as long as the patient remains on IS therapy.
– Peg‐interferon is not recommended in transplant candidates due risk of rejection.
*Monitoring:
– Regular follow‐up and monitoring for response to antiviral therapy HBV DNA, HBVsAg and continue HCC surveillance
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
HBeAg positivity which indicates active viral replication. While anti-HBe positivity indicates the presence of the non-replication phase. The presence of these markers with HBsAg indicates chronic active hepatitis
Donor with chronic active hepatitis:
-Fulminant hepatitis B infection had been reported in a naïve recipient who received kidneys from donors with HBsAg (+)/HBeAg (+) donors due to high infectivity rate.
-This organ can be accepted in urgent need for KT under the cover of antiviral therapy and HBIG.
– Discard the organ if recipient is naïve individual.
Recipient with chronic active hepatitis:
It will be managed the same ensure the following:
– Viral load HBV DNA must be checked.
– Co-infection with HDV. HCV
– Recipient must be referred to hepatologist and specialist in viral hepatitis for full evaluation.
-Must have liver disease staging, liver US
-Antiviral therapy tenofovir or entecavir should be initiated.
– If patient had decompensated liver disease may benefit from combined organ transplantation.
How would you manage this case?
-All candidates must have the following tests:HBsAg,HBeAb, HBeAg, HBeAb and HDV Ab serology, and HBV DNA levels.
– Naïve recipient ideally to be vaccinated pre-transplantation.
– Post-Tx antiviral prophylaxis and monitoring of viral load, liver enzymes and US.
References:
– Mahboobi N, Tabatabaei SV, Blum HE, Alavian SM. Renal grafts from anti-hepatitis B core-positive donors: a quantitative review of the literature. Transpl Infect Dis. 2012 Oct;14(5):445-51. doi: 10.1111/j.1399-3062.2012.00782.x. Epub 2012 Sep 12. PMID: 22970743.
– Guidelines for Hepatitis B & Solid Organ Transplantation British Transplantation Society Guidelines 2018.
– Srisuwarn P, Sumethkul V. Kidney transplant from donors with hepatitis B: A challenging treatment option. World J Hepatol. 2021 Aug 27;13(8):853-867. doi: 10.4254/wjh.v13.i8.853. PMID: 34552692; PMCID: PMC8422915.
– Song JE, Kim DY. Diagnosis of hepatitis B. Ann Transl Med. 2016 Sep;4(18):338. doi: 10.21037/atm.2016.09.11. PMID: 27761442; PMCID: PMC5066055.
Excellent answer, Hadeel, well done
Will you accept this DBD donor?
o If need demands, kidney transplantation of the HBsAg positive organ donor can be used for any recipient, after an individualised assessment of risk and benefit
o There is a significant published literature describing the outcome of HBsAg positive kidney donation to HBV immune recipients. In the majority of cases, antiviral prophylaxis has been given after transplantation. Chronic HBV infection appears to be an infrequent outcome, and the need for post-transplant antiviral treatment is not clearly established. If antivirals are not used or if antivirals are stopped after a period of prophylaxis, the recipient should receive long-term monitoring for the appearance of HBsAg
o Kidney transplantation from HBsAg positive donor to a non-immune recipient will result in chronic infection of the recipient. In this setting, antivirals should be given to prevent HBV-related liver damage
o Tuncer and colleagues demonstrated the safety of the use of HBsAg-positive organs in 35 recipients with an anti-HBs titer greater than 10 mIU/mL and negative donor HBV DNA. Recipients with an anti-HBs titer less than 10 mIU/mL were vaccinated to raise their titer to greater than 10 mIU/mL. HBIG and lamivudine were not used in this study. No recipient developed de novo HBV infection or HBV-attributed complications over the 2-year duration of the study
o Transplantation of a HBsAg-positive graft into a HBsAg-negative patient carries a significant risk of de novo infection without adequate prophylaxis. Despite the protection acquired from HBV vaccination or prior exposure to HBV infection, many centers remain reluctant to use HBsAg-positive grafts
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
o All HBsAg positive patients undergoing transplant work up must have the following tests: HBeAg, HBeAb and HDV Ab serology, and HBV DNA levels
o HDV RNA testing must be performed in potential transplant recipients where HDV serology is positive or equivocal
o In patients with positive HBsAg and undetectable HBV DNA, prophylactic therapy is recommended. In patients with HBsAg positivity and HBV DNA less than 2000 IU/mL, preemptive therapy is recommended. In patients with HBV DNA greater than 2000 IU/mL, treatment is recommend. Treatment with an antiviral HBV agent with a high genetic barrier to resistance is preferred ( Tenofovir Entecavir)
o In case of seropositivity, additional serologic markers including anti-HBc (IgM and IgG), HBeAg/ anti-HBeAb, anti-HbsAb, quantitative HBV-DNA PCR and liver biochemistry including transaminases, ALP, GGT and bilirubin to differentiate between active and inactive liver infection
o Active carrier state is defined as HBsAg(+) in the presence of HBeAg(+) or HBeAb, with HBV viral load above 20000 IU/mL with or without elevated alanine aminotransferase (ALT) levels whereas inactive carriers are HBsAg(+) and negative for HBeAg(-) with persistently low viral load, normal liver enzymes and low anti-HBc IgM or anti-HBc IgG levels
o In active HBV carriers, antiviral therapy is indicated until HBeAg becomes negative and viral replication is suppressed. Inactive carriers should be monitored with HBV-PCR and liver enzymes
o The donation of non-liver solid organs from an HBsAg positive donor to an HBsAg positive recipient can be undertaken as long as antivirals are used to suppress HBV after transplantation. In this setting, there appears to be no adverse impact on graft or patient survival
o HBsAg positive and/or HBV DNA positive candidates should be referred to a specialist with expertise in the management of liver disease and HBV infection to determine appropriate antiviral treatment
o CHBV and past HBV are not contraindications for SOT
o Individuals undergoing non-liver SOT who are HBsAg positive must have liver disease staging and suppression of HBV DNA by either tenofovir or entecavir before transplantation if there is a standard clinical indication
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
No, management is the same
What is your differential diagnosis?
1. False positive HBSAg
2. HBV/HDV
3. Early stage of HBV infection
How would you manage this case?
o Discuss with a specialist in viral hepatitis
o Recipient counseling
o Do HDV RNA
o Vaccination according to HBsAb titres
o HBsAg and undetectable HBV DNA, give therapy is recommended
o HBsAg positivity and HBV DNA less than 2000 IU/mL give pre-emptive therapy
o If HBV DNA greater than 2000 IU/mL treatment is recommend
o Treat with an antiviral HBV agent that have a high genetic barrier to resistance (Tenofovir Entecavir)
o Antiviral medications include: Lamuvidine, entecavir, adefovir dipivoxil, tenofovir disoproxil fumarate, telbivudine
References
1. BTS/RA Living Donor Kidney Transplantation Guidelines 2018
2. Guidelines for Hepatitis B & Solid Organ Transplantation. British Transplantation Society Guidelines, 2018.
3. Song JE, Kim DY. Diagnosis of hepatitis B. Ann Transl Med. Sep;4(18):338. doi: 10.21037/atm.2016.11. PMID:27761442;PMCID: PMC5066055.
4. Marinaki S, Kolovou K, Sakellariou S, Boletis JN, Delladetsima IK. Hepatitis B in renal transplant patients. World J Hepatol. 2017 Sep 8;9(25):1054-1063. doi: 10.4254/wjh.v9.i25.1054. PMID: 28951777; PMCID: PMC5596312.
5. Walid S. Ayoub, Paul Martin, Kalyan Ram Bhamidimarri. Hepatitis B Virus Infection and Organ Transplantation
Thanks, Mohamed
Excellent answer, but what is the accepted level of HBsAb (immune patient) in order to proceed with transplantation from HBsAg positive donor?
Will explain in more depth what would you do if the DBD donor is HBsAg and HBeAg positive.
Will you accept this DBD donor?
In the current index case of potential HBVsAg positive donor and presumed HBVsAg negative recipient: I will not accept the offer since transplanting an HBsAg-positive allograft into an HBsAg-negative recipient carries a significant risk of de novo infection. Even in the presence of preexisting acquired immunity after vaccination or after previous HBV infection should protect the recipient from primary de novo HBV infection, most transplant centres do not transplant kidneys from HBsAg-positive donors, and in most countries these donors can be transplanted only in matched HBsAg-positive recipients.
Will you accept this donor as a live donor if the recipient is also HBsAg positive?
The donor has HBVsAg positive to recipient with HBVsAg positive, The answer is yes, I can accept the offer provided that:
-With use of long life prophylactic anti-viral therapy entecavir which can confer long-term survival benefits.
-Or successfully immunized recipients (HBs Ab > 10 IU/ml and no need for prophylaxis.
Individuals undergoing non-liver solid organ transplantation who are HBsAg positive must have liver disease staging and suppression of HBV DNA by either tenofovir or entecavir before transplantation (BTS).
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
Evidence of chronic HBV, if confirmed on two samples six months apart. We can proceed for transplantation with prophylaxis anti viral to prevent replication with close monitoring.
What is your differential diagnosis?
HBVsAg in the deceased donor can be active HBV infection or if it more than 6 months denoting chronic infection.
How would you manage this case?
-The appropriate matching of recipient with a donor positive for HBsAg should be discussed with a specialist in viral hepatitis.
-All potential recipients should be counselled during the assessment process about the possibility of receiving a kidney from a donor with past or current HBV infection.
-Commence anti-viral prophylaxis for recipient mostly long life to prevent viral replication with close monitoring with virology markers ,ALT and DNA.
Thanks, Mohamed
I disagree with the first part of the answer. I would accept HsAg positive deceased donor into an immune recipient (adequate HBsAb preferable >100 unit/ml) or into HBsAg positive recipient.
Surprisingly, you came nicely regarding the rest of the scenario in spite being difficult
Will you accept this DBD donor?
I will accept this potential donor.
If need demands, the non-liver solid organs of the HBsAg positive organ donor can be used for any recipient, after an individualised assessment of risk and benefit(1).
Will you accept this donor as a live donor if the recipient is also HBsAg positive?
I will proceed in the transplant process provided that both the recipient and donor are positive for HBsAg and no evidence of HDV infection. Based on BTS guidelines as it is recommended that the kidneys, heart and lungs from the HBcAb positive organ donor can be used for any recipient, and the risk of de novo HBV infection is low. HBsAg positive donors should not be used for HBV/HDV co-infected recipients(1).
If yes, what are the conditions that should be met?
The following conditions have to be met(2):
a) Liver disease staging and suppression of HBV DNA: Individuals undergoing non-liver solid organ transplantation who are HBsAg positive must have liver disease staging and suppression of HBV DNA by either tenofovir or entecavir before transplantation if there is a standard clinical indication(1).
b) Individualised assessment of risk and benefit: If need demands, the non-liver solid organs of the HBsAg positive organ donor can be used for any recipient, after an individualised assessment of risk and benefit.
c) Antiviral prophylaxis(lamivudine prophylaxis): lamivudine prophylaxis may be given for six months after transplantation, although the risk of transmission is very low.
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
HBeAg positivity reflects the ongoing viral replication. This test is mostly replaced by the quantitative viral load(HBV DNA). Positive HBeAg or detectable viral load put the recipient at high risk of having post-transplant HBV infection. So, waiting for HBV DNA level to be undetectable is advisable. If need demands, antiviral medications and HBIG can be used while proceeding in the transplant process(2).
What is your differential diagnosis?
a) Acute HBV infection.
b) HBeAg-negative chronic HBV infection.
How would you manage this case?
1. To screen for co-infection with HDV.
2. The patient is immunocompromised, so antiviral medications (entecavir or tenofovir) should be started.
Antiviral treatment is indicated in certain subgroups of patients with acute HBV infection:
a) Fulminant hepatitis B
b) Severe AHB – based on the presence of at least two of the following criteria:
· bilirubin >100 μmol/L
· international normalised ratio (INR) ≥1.6
· hepatic encephalopathy
c) Protracted disease course – persistent symptoms or marked jaundice for more than four weeks after presentation
d) Immunocompromised host
Therapy should be continued for at least three months after seroconversion to HBsAb or 12 months after anti-HBe seroconversion without HBsAg loss(1).
References
1. Guidelines for Hepatitis E & Solid Organ Transplantation; first edition (BTS guidelines)
2. Srisuwarn P, Sumethkul V. Kidney transplant from donors with hepatitis B: A challenging treatment option. World J Hepatol. 2021 Aug 27;13(8):853-867. doi: 10.4254/wjh.v13.i8.853. PMID: 34552692; PMCID: PMC8422915.
Thanks, Safi for your excellent answer
Regarding a living donor with HsAg positive. What are the kidney diseases that could happen due to HBV infection?
Will you give the kidney with high HBV DNA to any recipient with a cover of antiviral treatment?
Support your answers by evidence, please.
Will you accept this DBD donor?
Yes, but before that need to know the recipient status
If recipient is HBsag +ve and don’t have active infection and there is no co infection with HDV- can proceed for transplant
If recipient is HbsAg -ve the donation can be accepted in special circumstances judging the risk against benefit like viral transmission, vascular access problem, long waiting time for transplantation, age of patients, comorbidities, degree of sensitization, vaccination status, most important is inform consent of HBV infection and need of antiviral medication
Antiviral for prevention of infection and reactivation to be given for life long and in case of vaccinated individual for one year. Pre transplant booster vaccination.
With monitoring of HBsAg and HBcAb 3 monthly for 1 year then and HBV DNA (NAT) 6 monthly
Moreover, meanwhile the transplantation is ongoing we need to recheck the HbsAg if it false positive or need to do viral DNA PCR from store donor sample
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
Yes, first of all the donor and recipient should have HBV DNA PCR for virus load, if it is positive and high, better to treat the donor and recipient with antiviral before the transplantation.
Both should not have active HBV infection, coinfection with HDV and liver enzyme are in normal limits.
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
Yes
The recipient should be treated with HBV immunoglobulin if anti Hbs is less than 100 IU
What is your differential diagnosis?
1.Early HBV infection
2.Results can be falsely positive for HBsAg
3.Recent vaccinated donor with false positive result
How would you manage this case?
MDT meeting with hepatologist or microbiologist or infectious disease specialist
Counseling the recipient and take inform consent for the possibility of HBV infection
A pre-transplant vaccine booster should be administered
Antiviral for prevention of infection and reactivation to be given for life long and in case of vaccinated individual for one year. Pre transplant booster vaccination.
Start entecavir or tenofovir alafenamide at transplant for DCD or before in living donation if HBV load is high
Close monitoring of HbsAg, Anti HBc 3 monthly then HBV DNA (NAT) 6 monthly along with LFT monitoring post-transplantation.
HBVv immunoglobulin to be administer if recipient immune status is not known or vaccinated with anti HBs <100 IU
References:
1.Lecture : Prof May A Hassbola: kidney transplant in patient with HBV
2.Veroux, M., Ardita, V., Corona, D., Giaquinta, A., Ekser, B., Sinagra, N., … & Veroux, P. (2016). Kidney transplantation from donors with hepatitis B. Medical Science Monitor: International Medical Journal of Experimental and Clinical Research, 22, 1427.
Thanks, Sumit
Regarding a living donor with HsAg positive. What are the kidney diseases that could happen due to HBV infection?
Thank you for the question, Prof,
Membranous glomerulopathy
Membranoproliferative GN
Iga Nephropathy
Polyarthritis nodosa
Acute hepatitis- pigment nephropathy
Chronic hepatitis- cirrhosis- HRS
Acute hepatitis – Herbal medication for Jaundice in our region- AIN
so, we need to counsel the donor as well for the risk of these disease due to hepatitis B virus.
Will you accept this DBD donor? Yes. Recipients with HBV immunity from vaccination may receive kidney transplant from donors with chronic infection. However, prophylaxis with antiviral agents and hepatitis B immunoglobulin is necessary. Recipients without prior infection or immunity should generally avoid transplant from donors with positive HBsAg except in extreme and urgent circumstances such as vascular access exhaustion.
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
Yes, and the conditions will include:
1. Rule out an active infection in both the donor and recipient using the HBV DNA. If DNA level is high, it’s better to treat to undetectable viral loads before transplantation except in extreme circumstances.
2. A donor or recipient with active infection should also be screened for other viruses such as HIV, HCV, HEV. Do liver scan, LFT to also assess for cirrhosis. Presence of decompensated cirrhosis might require simultaneous liver and kidney transplantation.
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management? No, it won’t. Though, this signifies active replication, HBV does not replicate in the kidneys, so if the recipient is immune from vaccination or previous infection transplant can still go ahead. However, in a recipient without prior infection or vaccination, transplant should occur in extreme cases only.
What is your differential diagnosis?
How would you manage this case?
Recipients with HBV immunity from vaccination may receive kidney transplant from donors with chronic infection. However, prophylaxis with antiviral agents using either entecavir or tenofovir alafenamide and hepatitis B immunoglobulin is necessary. Recipients without prior infection or immunity should generally avoid transplant from donors with positive HBsAg except in extreme and urgent circumstances such as vascular access exhaustion. They should also receive prophylaxis.
Reference
Dear Dr Adeyemo
That is a very impressive answer.
You were offered kidneys from a 53-year-old male DBD (donor after brain stem death) donor who suffered from SAH (grade 5) complicating cerebral aneurysm. His retrieval S Cr was 78 µmol/L. Virology was reported as follows: HBsAg positive, HBsAb negative, HBcAb negative, both HBeAg and HBeAb are negative. Both HCV and HIV are negative.
Will you accept this DBD donor?
Yes; I will accept this donors kidneys, and well consider them to HBs Ag +ve recipient whom HDV co-infection is excluded. Otherwise can be given to HBsAg +ve recipient is special conditions- not tolerating dialysis, persistent uremia, or long time on list with prolonged dialysis time, or no dialysis access available, with recipient counselling and consent signed.
I shall review the medical file of the patient for ALT level, HBV DNA, to clarify his disease burden.
It is acceptable to have such donors in the presence of anti-viral therapy (tenofovir and entecavir) that suppress HBV replications, with no effect on graft and patient survival.
And the recipient should undergo frequent monitoring for appearance of HBs Ag.
Using HBsAg positive kidneys in patients with HBsAb immunity, showing good graft and patient survival using a combination of HBIG and lamivudine prophylaxis.
Life-long combination therapy with HBIG and a potent NA can be given to high risk patients for HBV recurrence:
(1) HBV DNA positive at time of transplant.
(2) HBeAg positive patients.
(3) Those transplanted for hepatocellular carcinoma.
(4) HIV co-infected.
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
Yes, I will accept his kidneys for HBs Ag +ve recipients. But I would start him on treatment for HBV to the donor, and ask for ALT, and HBV DNA.
Considering high risk for HBV reactivation, so anti- viral medications should be started immediately, and continued indefinitely, with frequent monitoring of HBV DNA and ALT at least every 3 months in the first year and 6 monthly thereafter.
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
I would ask for ALT level and HBV DNA level, and will start antiviral therapy in living donor to improve liver function and decrease reactivation after transplantation, in deceased donors I will explain the risk to the potential recipient, with a signed concent, and early start of antiviral medications
In this situation and by definition the donor then considered to have chronic active hepatitis B. renders the recipient at higher risk of fulminant hepatic failure/cirrhosis and HCC.
In this scenario expert opinion is a must, with multidisciplinary team discussion, and dicission.
References:
(1) European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu; European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017 Aug;67(2):370-398. doi: 10.1016/j.jhep.2017.03.021. Epub 2017 Apr 18. PMID: 28427875.
(2) Huprikar S, Danziger-Isakov L, Ahn J, Naugler S, Blumberg E, Avery RK, Koval C, Lease ED, Pillai A, Doucette KE, Levitsky J, Morris MI, Lu K, McDermott JK, Mone T, Orlowski JP, Dadhania DM, Abbott K, Horslen S, Laskin BL, Mougdil A, Venkat VL, Korenblat K, Kumar V, Grossi P, Bloom RD, Brown K, Kotton CN, Kumar D. Solid organ transplantation from hepatitis B virus-positive donors: consensus guidelines for recipient management. Am J Transplant. 2015 May;15(5):1162-72. doi: 10.1111/ajt.13187. Epub 2015 Feb 23. PMID: 25707744.
(3) Guidelines for. Hepatitis B & Solid Organ. Transplantation. British Transplantation Society Guidelines
Thanks, Mohamed
Regarding a living donor with HsAg positive. What are the kidney diseases that could happen due to HBV infection?
Thank you Prof. Ahmad
the diseases could happen due to hepatitis B infection form a donor HBsAg +ve are:
Reference:
UpToDate –Kidney transplantation in adults: Hepatitis B virus infection in kidney transplant recipients
The index patient is being offered a DBD (donor after brain death) donor with good terminal renal function. The donor is HBsAg positive. Other serological tests (HBsAb, HBcAb, HBeAg, HBeAb, HIV and HCV) are negative.
Positive HBsAg signifies past HBV infection.
As per the British Transplantation Society guidelines, kidneys from HBsAg positive donors can be used for any recipient, after risk and benefit assessment (1).
Hence, I will accept this DBD donor, especially if the recipient has urgent need of transplant (poor vascular access, uremia despite adequate hemodialysis, poor tolerability for dialysis) (2).
Such a donor should not be used if the recipient is HBV/HDV co-infected (1).
Transplant recipient should receive Hepatitis B Immunoglobulin (HBIG) with antivirals (Tenofovir/ entecavir) as prophylactic treatment for HBV, especially non-protective anti-HBsAb titres and if the HBV DNA status of the donor is not known (1-3).
If the recipient is HBV immune, post-transplant antivirals need not be given, but the patient should be monitored closely and antivirals should be given on appearance of HBsAg.
Patient should be monitored with liver enzymes, HBsAg and HBV DNA once in 3 months for at least 1 year post-transplant, and subsequently as per the test reports (1,3).
Yes. A HBsAg positive live donor can be accepted for HBsAg positive recipient as long as antivirals are used to manage HBV replication post-transplant (1).
There is high risk of reactivation of HBV, hence HBsAg positive patients who did not require antivirals pre-transplant should be started on antivirals (tenofovir or entecavir) at time of transplant and continued indefinitely, irrespective of HBV DNA levels (3).
Patient should be monitored with liver enzymes and HBV DNA once in 3-6 months and ultrasound abdomen once in 6 months (2,3).
In nutshell, this clinical scenario requires:
1) Recipient should be counselled regarding the clinical scenario.
2) Hepatologist should be involved in management.
3) Post-transplant antiviral prophylaxis would be required.
4) Regular post-transplant monitoring of LFT and HBV DNA should be done as per protocol.
Positive HBeAg and HBeAb signify HBeAg positive chronic hepatitis with active viral replication. Such patients have high HBV DNA levels usually with liver damage, and progression to cirrhosis is possible (1).
If the donor is positive for HBsAg, HBeAg and HBeAb, I will accept this DBD donor, y if the recipient has urgent need of transplant (poor vascular access, uremia despite adequate hemodialysis, poor tolerability for dialysis) (2). The treatment protocol will remain same. The transplant recipient should receive Hepatitis B Immunoglobulin (HBIG) with antivirals (Tenofovir/ entecavir) as prophylactic treatment for HBV, especially non-protective anti-HBsAb titres and if the HBV DNA status of the donor is not known (1-3). If the recipient is HBV immune, post-transplant antivirals need not be given, but the patient should be monitored closely and antivirals should be given on appearance of HBsAg. Patient should be monitored with liver enzymes, HBsAg and HBV DNA once in 3 months for at least 1 year post-transplant, and subsequently as per the test reports (1,3).
If the recipient is positive for HBsAg, HBeAg and HBeAb, then a detailed hepatic evaluation is required prior to proceeding with kidney transplant. In such a patient, there may be a possibility of HBV-related liver disease, requiring a combined liver-kidney transplant (1).
References:
Excellent Amit
Assume that the potential recipient is not desperate for a kidney from HsAg positive titre and also HeAg. Will still go ahead and accept this infected organ?
Please substantiate your answer.
Thank you Professor.
Positive HBeAg and HBeAb signify HBeAg positive chronic hepatitis with active viral replication. Such patients have high HBV DNA levels usually with liver damage, and progression to cirrhosis is possible (1).
If the donor is positive for HBsAg and HBeAg, I will accept this DBD donor, only if the recipient has urgent need of transplant (poor vascular access, uremia despite adequate hemodialysis, poor tolerability for dialysis) after detailed patient counselling (2). If the recipient does not agree for such a patient, then the transplant will not be done.
References:
1-Will you accept this DBD donor?
yes
Hepatitis B surface antigen (HBsAg) is the serologic hallmark of HBV infection. It can be detected using an enzyme immunoassay (EIA).
HBsAg appears in serum 1 to 10 weeks after an acute exposure to HBV
In patients who subsequently recover, HBsAg usually becomes undetectable after four to six months.
Persistence of HBsAg for more than six months implies chronic infection.
The disappearance of HBsAg is followed by the appearance of hepatitis B surface antibody (anti-HBs). In most patients, anti-HBs persists for life, thereby conferring long-term immunity from reinfection. However, over time, anti-HBs may disappear in some patients, and they may have only isolated hepatitis B core antigen (anti-HBc) IgG.
2-Will you accept this donor as a live donor if the recipient is also HBsAg positive?
YES
3-If yes, what are the conditions that should be met?
4-Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
NO
Hepatitis B e antigen and antibody — Hepatitis B e antigen (HBeAg) is a secretory protein that is processed from the precore protein. It is an early antigen and not an envelope antigen. It is generally considered to be a marker of HBV replication and infectivity. The presence of HBeAg is usually associated with high levels of HBV DNA in serum and higher rates of transmission of HBV infection from carrier mothers to their babies and from patients to health care workers
HBeAg to anti-HBe seroconversion occurs early in patients with acute infection, prior to HBsAg to anti-HBs seroconversion However, HBeAg seroconversion may be delayed for years to decades in patients with chronic HBV infection. In such patients, the presence of HBeAg is usually associated with the detection of high levels of HBV DNA in serum and active liver disease.
5-What is your differential diagnosis?
Susceptible
Prior infection (inactive)
Immune due to hepatitis B vaccination
Acutely infected
Chronically infected
6-How would you manage this case?
HBV DNA assays use real-time PCR techniques
The diagnosis of chronic HBV infection is based upon the persistence of HBsAg for more than six months . Additional tests for HBV replication, HBeAg and serum HBV DNA and ALT, should be performed to determine if the patient should be considered for antiviral therapy.
All patients with chronic HBV infection should be regularly monitored because HBV DNA and alanine transaminase (ALT) levels vary during the course of infection to monitor for progression of liver disease
HBeAg-negative patients who have normal serum ALT and low (<2000 international units/mL) or undetectable HBV DNA are considered to be in an inactive carrier state. These patients generally have a good prognosis and antiviral treatment
Choice of regimen
For most kidney transplant recipients who require antiviral therapy to prevent de novo HBV infection, preferred antiviral regimens include entecavir and tenofovir. Antiviral therapy should be started at the time of transplantation.
administer treatment for one year
administer entecavir since it is not associated with kidney toxicity; dose adjustments are required for those with reduced kidney function
. If tenofovir is used, generally prefer tenofovir alafenamide to tenofovir disoproxil fumarate because it is associated with a lower risk of kidney toxicity.
Entecavir and tenofovir are preferred over lamivudine, which had previously been the mainstay of treatment, because lamivudine has been associated with a high rate of drug resistance with long-term use
Pegylated interferon alfa should not be used in kidney transplant recipients, because it may precipitate acute allograft rejection
. Adefovir should also be avoided due to its nephrotoxicity and its weak antiviral activity
REFERENCES UpToDate
Thank you. Your systematic approach is highly regarded. I wonder about your comment that you will not change management plans in case donor is HbeAg+ve! You discussed this point in details assuming this patient would indicate high viral replication and would be highly infectious, Do you still accept this patient as a donor?
PATIENT IS HIGH RISK DONOR
YES ,I WILL ACCEPT AS DONOR IF THERE IS OTHER OPTION
IF THERE IS CHANCE FOR TREATMENT DONOR BEFORE TRANSPLANT WILL BE BETTER
Considerations for donor selection — In general, kidney transplant recipients with prior (ie, hepatitis B surface antigen [HbsAg] negative, hepatitis B core antibody [anti-HBc] positive) or chronic (HBsAg positive) hepatitis B virus (HBV) infection may receive a kidney transplant from any donor regardless of the HBV status of the donor
Donors — Potential kidney donors (living and deceased) should be tested for HBsAg, anti-HBc, and HBV DNA nucleic acid testing (NAT); this approach is consistent with guidelines from the United States Centers for Disease Control and Prevention
For living donors, testing should be done within the 28 days before organ procurement
for deceased donors, testing should be performed within 96 hours before organ procurement. Frequently in deceased donors, only qualitative HBV DNA testing is performed since quantitative testing might delay donor decision-making.
In countries where there are barriers to access to the HBV DNA assay, testing for HBV DNA can be reserved for donors who are positive for HBsAg or anti-HBc.
It should be noted that HBV does not reside or replicate in the kidney, so the risk of HBV transmission is via residual blood and peripheral blood mononuclear cells in these organs despite flushing
Suitable donors — The suitability of a donor-recipient pair for kidney transplantation depends upon the HBV status of both the donor and recipient
Recipients with HBV immunity due to vaccination and recipients without evidence of prior infection or immunity should ideally receive a kidney transplant from the following donors:
●Living or deceased donors who have no evidence of prior HBV infection with or without immunity to HBV through vaccination (HBsAg negative, anti-HBc negative, anti-HBs positive).
●Living or deceased donors with prior HBV infection (HBsAg negative, anti-HBc positive). The risk of HBV transmission is negligible unless the donor is HBV DNA positive, in which case prophylactic antiviral therapy is recommended
REFERENCES UP TO DATE
2-Fairley CK, Mijch A, Gust ID, et al. The increased risk of fatal liver disease in renal transplant patients who are hepatitis Be antigen and/or HBV DNA positive. Transplantation 1991; 52:497.
Dear Hamada
There is no chance to treat the donor. He is a deceased donor. Please make your plan clear.
– Will you accept this DBD donor?
Yes ,Recent guidelines recommended that kidneys from HBsAg (+) donors can be transplanted to recipients with assessment of the risk and benefit along with an informed consent.
When allocated to serology-matched recipients, can have an excellent short-term outcome ,but for long term outcomes need to be furtherly evaluated
-Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
Yes, Treatment of HBsAg-positive renal transplant recipients with antiviral treatment confers long-term survival benefit, and tenofovir or entecavir is effective in cases with resistance to lamivudine.
Antiviral therapy with lamivudine is effective in suppressing HBV DNA and decreasing elevated liver enzymes , and can improve graft survival almost comparable to HBsAg-negative recipients
In spite that antiviral treatment need to be continued for life post renal transplant due to the risk of HBV reactivation and worsening of disease course , another study demonstrated a successful withdrawal of antiviral treatment in 4 HbsAg-positive renal transplant recipients with complete suppression of HBV infection after being on antiviral therapy for 14.3 months, the cases maintained HBV-DNA negative for a median of 60.5 months .
Studies evaluating the transplantation of HBsAg-positive kidney donors to HBsAg-positive recipients with natural immunity is rational and mostly safe.
-Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
If the donor has HBe Ag ,HBe Ab and HBsAg positive ,indicating active hepatitis with viral replication and likely to progress to chronic hepatitis ,HBV DNA level need to be tested
The donor has to be treated before donation to have a sustained viral response .
The recipient and the donor have to be counselled .
The transplantation can be done if the donor is cured and the antibody titer of the recipient, just before transplantation, is at least 10 IU/ml and with concomitant administration of one dose of booster vaccination in combination with hepatitis B hyperimmune globulin(HBIG) .
Antiviral prophylaxis postoperatively need to be started . The need and the duration of antiviral treatment in this patient population have not been investigated; moreover, data about monitoring long term are lacking. It seems logical to assume that antibody titer should be checked and booster vaccination should be administered when the titer falls below 10 IU/ml, since transplant recipients receiving immunosuppression are at risk for viral reactivationif it has been transmitted from the donor.
HBeAg‐positive patients should be treated until HBV DNA and HBeAg are cleared and anti‐HBe seroconversion occurs. Additional treatment is needed for at least 6–12 months after anti‐HBe seroconversion to prevent virological reactivation.
-What is your differential diagnosis?
HB s Ag indicates infection risk
Chronic hepatitis B virus infection
Acute Hepatitis B virus infection
Incubation period of HBV infection
Coinfection of HBV and HDV
-How would you manage this case?
The recipient need to be counselled and hepatologist need to be involved
The recipient ‘s virological status need to be assessed beside the routine assessment tests by checking HBsAg ,HBcAb ,HB s Ab ,HB e Ag ,HBe Ab and HBV DNA level.
If the anti-HBs is > 100 mIU/mL, transplantation can proceed without antiviral prophylaxis. However, if HBV DNA was not measured by a method of optimum low detection limit or the result of HBV DNA cannot be obtained , antiviral as tenofovir or entecavir can be prescribed to decrease HBV transmission risk .
In the setting of HBsAg (+)/HBV DNA (+) donor, antiviral prophylaxis with or without HBIG will be needed among patients with different levels of anti-HBs concentration
Antiviral treatment along with HBVIg can be given HBIG provides passive immunity for a high concentration of anti-HBs that are aimed to act as neutralizing antibodies to HBV
Naïve recipients or previously immune recipients who have anti-HBs concentration less than 10 mIU/mL while the KDIGO guideline suggested Anti-HBs Ab concentration <100 mIU/mL can decrease rapidly to a non-protective level and may require a booster dose .
HBs Ab monitoring at least yearly is needed . A further booster dose of vaccine may be required, by either a single-shot high dose (40 µg) or a total complete course with a follow-up level at 4-wk after a complete course of treatment.
Reference
-Srisuwarn P, Sumethkul V. Kidney transplant from donors with hepatitis B: A challenging treatment option. World J Hepatol. 2021;13(8):853-867.
– Veroux M, Ardita V, Corona D, et al. Kidney Transplantation From Donors with Hepatitis B. Med Sci Monit. 2016;22:1427-1434. Published 2016 Apr 28.
– Marinaki S, Drouzas K, Skalioti C, Boletis JN. Hepatitis B and C in Kidney Transplantation. Advances in Treatment of Hepatitis C and B [Internet]. 2017 Mar 8.
I appreciate your clinical approach.
I did not understand the need for HBV DNA level if HbeAg is positive
Live donor with HbsAg+ve:
HBeAg & HBeAb positive in addition to HBsAg+ve:
References:
I appreciate your clinical approach.
I did not understand the need for HBV DNA level if HbeAg is positive
Yes . Although transplanting HBsAg negative kidney recipients from HBsAg positive deceased donors carries significant risk of denovo infection , total exclusion of HBsAg donors from the donor pool would significantly reduce the supply of kidney allografts especially in endemic areas . Immunization status of the recipient either due to vaccination or previous infection and proper prophylaxis post kidney transplant will play an important protective role .
–Acute or chronic HBV infection
-Combined HBV and HDV infection
Reference :
3. Viral Hepatitis : Guidelines by the American Society of Transplantation Infectious Disease Community of Practice
Yes MDT approach is good. One many have to decide at 3 am that MDT would not be possible at that time. However, I shall take opinion of other colleagues and experts to help in decision-making.
Yes .totally agree .thank you prof. Ajay
Donor stauts
HBsAg positive
HBsAb negative
HBcAb negative
HBeAg and HBeAb are negative.
HCV and HIV are negative.
Will accept as donor if the following criteria are met.
Better to arrange further testing of donor with HBs Ab and HBV DNA level with immune status of recipient before transplantation .
Recipient vaccination status and recipient serology of HBV.
If the recipient is also positive for HBsAg than one can proceed also with the prophylaxis treatments
It is widely acknowledged that there is a sizable risk of novo infection when an HBsAg-positive allograft is transplanted into a recipient who is HBsAg-negative.
The recipient should be protected from primary de novo HBV infection by preexisting acquired immunity from vaccination or prior HBV infection, but most transplant centers do not transplant kidneys from HBsAg-positive donors, and in most nations these donors can only be transplanted into matched HBsAg-positive recipients.
Lamivudine antiviral medication is efficient in reducing transaminase levels and lowering HBV DNA. It is also linked to increased graft survival that is almost on par with HBsAg-negative patients.
Live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
Yes we can proceed for transplantation in very high risk condition as risk of De novo disease is very high.
Conditions in which this donor is accepted are;
Recipient has a long waiting period.
Age
Other co morbidities
Dialysis risk and vascular access problem
HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
This patient have acute infection and seroconversion and he need treatemt befor proceding to transplantation
The recipient needs to be warned about the elevated risk of infection and other problems and start taking Entecavir or tenofovir as soon as possible after the transplant.
Differentials are
HBV
HVE
HBV with co-infection
Management;
Counselling
Multidisciplinary team approach
Antiviral treatment
References;
Huprikar S, Danziger-Isakov L, Ahn J, et al. Solid organ transplantation from hepatitis B virus-positive donors: Consensus guidelines for recipient management. Am J Transplant. 2015;15:1162–72
Fabrizi F, Dulai G, Dixit V, et al. Lamivudine for the treatment of hepatitis B virus-related liver disease after renal transplantation: meta-analysis of clinical trials. Transplantation. 2004;77:859–64.
42. Yap DY, Tang CS, Yung S, et al. Long-term outcome of renal transplant recipients with chronic hepatitis B infection- impact of antiviral treatments. Transplantation. 2010;90:325–30.
British Transplantation Society Guidelines: Guidelines for Hepatitis B & Solid Organ Transplantation 2018.
Yes MDT approach is good. One many have to decide at 3 am that MDT would not be possible at that time. However, I shall take opinion of other colleagues and experts to help in decision-making.
Will you accept this DBD donor?
Yes, But if the need demands
If the donor is considered for liver Tx and the recipient is HBsAg+ve
If HBeAg +ve, HBeAb +ve
Differential diagnosis
This patient had an active chronic hepatitis B infection.
Reference
BTS guideline, Hepatitis B and SOT 2018
I appreciate your clinical approach.
I did not understand the need for HBV DNA level if HbeAg is positive
DBD donor:
HBsAg positive, HBsAb negative, HBcAb negative, both HBeAg and HBeAb are negative. Both HCV and HIV are negative.
Will you accept this DBD donor?
Yes, I will.
Simply, the non-liver solid organs of the HBsAg positive organ donor can be used for any recipient, after an individualized assessment of risk and benefit.
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
Yes, I will.
We should request HBV DNA for the donor and herein, we have three possibilities for our recipients.
1-HBsAg positive recipient: Many studies shown safety of transplantation without elevation of transaminases but we consider antiviral treatment with Entecavir and clinical follow up with HBV DNA and liver function testes.
2-HBsAb positive with titer <10 IU/L: Consider vaccination, prophylaxis with high dose Immunoglobulin or Lamivudine and strict follow up by HBV PCR and liver function test.
3-HBcAb or HBsAb >10 IU/L: No need for prophylaxis and just clinical follow up with HBV DNA and liver functions.
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
Active infection with viral replication, No, the management remained the same regardless the DBD donor HBeAg/Ab status i.e., I will accept the DBD donor, the recipient must counseled about high risk of infection and complications that might be occurred and get Entecavir or tenofovir right away from the time of transplantation.
What is your differential diagnosis?
– False positive HBsAg results.
– Early stage of HBV infection.
– HBV and HDV co-infection.
How would you manage this case?
–Refer to hepatology consultant.
-Counseling the recipient about the possibility of HBsAg-positive organs
-Pre-transplant vaccine booster dose according to HBsAb titer.
-Start with Entecavir directly according to GFR.
-Close monitoring of HBV DNA and LFT post-transplantation and treat accordingly.
References:
1- British Transplantation Society Guidelines: Guidelines for Hepatitis B & Solid Organ Transplantation 2018.
2-Veroux M, Ardita V, Corona D, et al. Kidney Transplantation From Donors with Hepatitis B. Med Sci Monit. 2016;22:1427-1434. Published 2016 Apr 28. doi:10.12659/msm.896048.
I appreciate your clinical approach.
I will accept the donation. If the recipient is negative for HB s antigen and HBs antibodies then transplant can be planned with HBV immunoglobuline and Lamivudine prophylaxis.
If recipient is positive for Hbs antigen then transplantation with treatment protocol depending on other parameters of HBV DNA and HBVe antigen level to determine the suitable protocol of treatment.
HBe ang positive donor indicate active replication of the virus . Transplanting from such a donor is bearing high risk of infection in HBV naive recipient and its highly indicated to administer both HBIG and Lamivudine prophylaxis.
If the recipient is immunized with HBV antibodies titer of more than 100 then transplanting a kidney from HBs ag positive/HBV DNA negative donor can proceed transplantation with no prophylaxis but with close follow up.
‘Brevity for the sake of clarity’, I admire you for that approach.
Please use headings and sub-headings to make easier to read your write-up. Please use bold or underline to highlight headings and sub-headings.
You were offered kidneys from a 53-year-old male DBD (donor after brain stem death) donor who suffered from SAH (grade 5) complicating cerebral aneurysm. His retrieval S Cr was 78 µmol/L. Virology was reported as follows: HBsAg positive, HBsAb negative, HBcAb negative, both HBeAg and HBeAb are negative. Both HCV and HIV are negative;
NDD w Virology was reported as follows:
HBsAg + ve HBs Ab -ve , HBc Ab -ve
HBe Ag -ve , HBe Ab -ve
HCV -ve , HIV -ve
We need Donor HDV Ab serology and HBV DNA levels.
Before we accept the HBsAg positive donor, better to know the immune status of the recipient.
Will you accept this DBD donor?
Yes, but depending on recipient HBV status;
If recipient is vaccinated with anti HBs titer is more than 10 mIU/ml.
If Had chronic infection in past with lifelong antiviral therapy.
If Prior infection and immunity with antiviral therapy during intense IS.
YES, After Signing Exceptional Distribution Risk Consent (ExD) =>
If no immunity or not vaccinated, would need immunoglobulins and antiviral therapy if transplant occurred. HBV DNA, HBsAg and anti HBc should be checked every 3 months.
The non-liver solid organs of the HBsAg positive organ donor can be used for any recipient, after an individualized assessment of risk and benefit. (2C)
Individuals undergoing non-liver solid organ transplantation who are HBsAg positive must have liver disease staging and suppression of HBV DNA by either Tenofovir or Entecavir before transplantation if there is a standard clinical indication. (1B)
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
YES,
I will accept if HBs Ag positive Donor to HBsAg positive recipient,
Individuals undergoing non-liver solid organ transplantation who are HBsAg positive must have liver disease staging and suppression of HBV DNA by either Tenofovir or Entecavir before transplantation if there is a standard clinical indication. (1B)
HBsAg positive donors should not be used for HBV/HDV co-infected recipients. (1C)
It will need lifelong antiviral therapy if the recipient is established chronic infection, to do so will have to do Anti HBs, Ant HBc antibodies and DNA PCR.
In case of live donor HBV negative recipient should be vaccinated prior to transplantation. HBV DNA, HBsAg and anti HBc should be checked every 3 months.
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
YES,
Management will be changed; because this high risk for HBV recurrence.
(HBeAg) and (anti-HBe or HBeAb);
Useful in monitoring chronic HBV infection, especially during antiviral therapy.
The presence of HBeAg relates to viral replication.
Patients with HBeAg are generally considered to be more infectious than those with anti-HBe and without HBeAg.
Life-long combination therapy with HBIG and a potent NA can potentially be given to patients who were traditionally considered at high risk for HBV recurrence. (2B)
Individuals with decompensated cirrhosis and detectable HBV DNA require urgent antiviral treatment with NA(s). Entecavir and tenofovir are the first line antiviral agents and should be continued indefinitely. (1A)
Individuals with decompensated cirrhosis due to hepatitis B should be treated in specialist liver units as the application of antiviral therapy is complex and these patients may be candidates for liver transplantation. (1C)
Patients with advanced HBV-related liver disease requiring another organ transplant be considered for combined transplantation after careful consideration of the potential risks and benefits. (2C)
What is your differential diagnosis?
Considered at high risk for HBV recurrence,
HBe Ag positive patients,
HBV DNA positive at time of transplant,
Those transplanted for hepato-cellular carcinoma or,
Those who are HIV co-infected.
How would you manage this case?
In HBsAg positive individuals deemed to be at high risk of recurrence, combination therapy with HBIg and/or a potent NA is recommended from the time of transplantation to prevent HBV reinfection post-liver transplant. (1B)
Individuals with fulminant liver failure associated with hepatitis B infection must be managed in a specialist liver centre. (1C)
HBV/HDV recipients should receive combination HBIg/NA prophylaxis from time of transplantation. (1C)
For HBV/HDV infected recipients HBIg withdrawal from combination HBIg/nucleo(t)side analogues (NA) prophylaxis can be considered, but not within 12 months of transplantation. (2C)
HBV DNA and HBsAg should be monitored every three months in the first year and thereafter every six months in HBsAg positive liver transplant recipients or individuals receiving a graft from a HBcAb positive donor, regardless of treatment or prophylaxis regimen. (1C)
Amongst renal transplant recipients who are HBcAb positive, if HBsAb are < 100 IU/mL, then vaccination should be considered to boost the protective titre of HBsAb and minimize the risk of reactivation. (2C)
In those who fail to respond to the initial HBV vaccination schedule, a second series should be administered. (2C)
References;
*British Transplantation Society Guidelines: March 2018.
*UpToDate.
I like your well structured detailed summary.
I appreciate level of recommendation in relation to each advice in relation to the type of disease and corresponding mode of treatment indicated.
Typing whole sentence in bold amounts to shouting.
Chronic HBV is not uncommon and its prevalence vary according to the region ranging from 1.2-2.6% in Europe and up to 4.6-7.6% in Africa
Goal of management
Transplant recipient evaluation with positive HBsAg
Donor evaluation
Approach for transplanting kidney from HBsAg positive donor to naive transplant recipient
The main challenge is transmission of HBV from donor to the recipient which is lower in kidney compared to liver transplantation but still can occur so the following approach should be done in order to improve outcome:
A- Evaluation of the donor risk
B- Selecting the appropriate recipient
C- Use of prophylactic therapy at the time of transplantation including
Prophylaxis is indicated in the following
D- Monitoring
Prerequisites before accepting HBV positive donor to an HBV naive recipient:
As these criteria will put the patient at minimal risk of reactivation with either no or single antiviral agent for at least 1 year with close follows up every 3 months, except if the recipient is HBV positive at this situation I will initiate treatment before transplantation
Approach for transplanting kidney to transplant recipient with chronic (HBsAg positive, anti-HBc positive)
To conclude
I will do PCR for the donor and antiHBs to the recipient to evaluate the risk, if PCR is positive I will exclude this donor. If PCR is negative I will accept this DBD donor under the following circumstances
On the other hand, I will you accept this donor as a live donor if the recipient is also HBsAg positive since transplant recipients with chronic infection can receive kidney from any donor regardless of HBV status under cover of life long antiviral therapy with close monitoring, provided that there is no or compensated cirrhosis,
In case of decompensated cirrhosis , patient will be candidate for dual transplantation
An impotent point to be put in mind is that the risk on the donor since there is a possible risk of glomerulonephritis and PANS which can have bad impact on the kidney
If the donor HBeAg is positive in addition to positive HBsAg at that time I will exclude this donor since there are reported cases of fulminant hepatitis after transplantation from donors who were HBsAg and HBeAg positive.
References
1- Chan TM, Fang GX, Tang CS, et al. Preemptive lamivudine therapy based on HBV DNA level in HBsAg-positive kidney allograft recipients. Hepatology 2002; 36:1246.
2- Yap DY, Tang CS, Yung S, et al. Long-term outcome of renal transplant recipients with chronic hepatitis B infection-impact of antiviral treatments. Transplantation 2010; 90:325.
3- Liaw YF, Sung JJ, Chow WC, et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med 2004; 351:1521.
4- Loomba R, Rowley A, Wesley R, et al. Systematic review: the effect of preventive lamivudine on hepatitis B reactivation during chemotherapy. Ann Intern Med 2008; 148:519.
5- Han DJ, Kim TH, Park SK, et al. Results on preemptive or prophylactic treatment of lamivudine in HBsAg (+) renal allograft recipients: comparison with salvage treatment after hepatic dysfunction with HBV recurrence. Transplantation 2001; 71:387.
6- Chancharoenthana W, Townamchai N, Pongpirul K, et al. The outcomes of kidney transplantation in hepatitis B surface antigen (HBsAg)-negative recipients receiving graft from HBsAg-positive donors: a retrospective, propensity score-matched study. Am J Transplant 2014; 14:2814.
7- Shaikh SA, Kahn J, Aksentijevic A, et al. A multicenter evaluation of hepatitis B reactivation with and without antiviral prophylaxis after kidney transplantation. Transpl Infect Dis 2022; 24:e13751.
I like your analysis. However, you mention as I quote you, “Treatment of the donor and providing functional cure (sustained absence of HBsAg with or without the development of anti-HBs) before transplantation is the best.”
Do you really have enough time to treat DBD donor with anti-viral ?
No… I am talking about living donor with hepatitis Bs Ag, not deseced one
Oh yes for an LRD, of course Dr Yusuf.
4. You were offered kidneys from a 53-year-old male DBD (donor after brain stem death) donor who suffered from SAH (grade 5) complicating cerebral aneurysm. His retrieval S Cr was 78 µmol/L. Virology was reported as follows: HBsAg positive, HBsAb negative, HBcAb negative, both HBeAg and HBeAb are negative. Both HCV and HIV are negative.
====================================================================
History
====================================================================
Will you accept this DBD donor?
HBsAg positive, HBsAb negative, HBcAb negative
Both HBeAg and HBeAb are negative.
Both HCV and HIV are negative.
Yes I will accept this donor
====================================================================
Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
Yes
===================================================================
Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
==================================================================
What is your differential diagnosis?
====================================================================
How would you manage this case?
===================================================================
Reference
I like your analysis. However, you mention as I quote you, “HBV DNA beforehand; if it is positive, it is preferable to treat the donor before the donation.”
Do you really have enough time to treat DBD donor with anti-viral ?
Many thanks Prof.Sharma
NO
I’m referring to living donors who have hepatitis Bs Ag, not deceased donors
This DBD has isolated positive Hbs Ag and negative other antibodies so we should consider one of the following:
– Early hepatitis HBV infection or Hepatitis D co-infection with HBV
– False positive HBsAg results
An HBV-negative recipient could only receive a kidney transplant from a HbsAg-positive donor in extreme circumstances. There is a high probability of de novo infection with HBsAg-positive allografts in HBsAg-negative recipients.
Will accept the kidney donation if:
– Recipient is Hbs Ag positive
– If long time on the waiting list
– If recipient accept to take the risk of transplantation from Hbs Ag patient, being advised to take the treatment
Before kidney transplantation quantitative PCR HBV DNA is needed to look for viremia load.
Living donors who have positive Hbs Ag should have their viral loads confirmed by PCR HBV DNA. If this is the case, the donor should be treated before donating, and the efficacy of the therapy should be confirmed.
Patients receiving kidney transplants from HBsAg-positive, HBV-DNA positive donors exhibited similar graft and patient survival, acute rejection, and post-transplant sequelae to those receiving HBsAg-negative kidneys, despite a higher incidence of acute hepatitis.
In this context, the current clinical condition of donor is active hepatitis B infection which indicates that transplantation of donor with active Hep B carries high risk of infection transmission into immunocompromised patient. In this case donation is only given to waitlisted Hep B positive recipient on treatment or if the patient accepted the risk of infection.
This DBD has isolated positive Hbs Ag and negative other antibodies so we should consider one of the following:
o Early hepatitis HBV infection or Hepatitis D co-infection with HBV
o False positive HBsAg results
– Blood sample for PCR HBV DNA
– Donor Liver biopsy would be of great value for confirmation of Hepatitis B infection, during organ retrieval.
– Pre-transplant vaccination of recipient
– Prophylaxis with lamivudine or entecavir post-transplantation
– Monitoring of liver enzymes and viral load after transplantation
I like your analysis. However, you mention as I quote you, “PCR HBV DNA. If this is the case, the donor should be treated before donating, and the efficacy of the therapy should be confirmed..”
Do you really have enough time to treat DBD donor with anti-viral ?
Thank you Dr for your comment. In regards to PCR HBV DNA, needed to confirm the viral load and nor for treatment, in other words, to assess the risk of infection activation after transplantation.
However for living donation, it is used as baseline and for followup on treatment.
1) Will you accept this DBD donor
Yes, if the following conditions are met:
HBsAg positive organ has been included in extended criteria for organ donation because of a gross imbalance between kidneys needed and those available for transplantation. Moreso, this is a diseased donation, there is no sufficient time to start running a further investigation on the donor. Although blood samples can be collected for a retrospective test like HEV RNA, anti-HBe, and HBV DNA
2) Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met
In this situation, there is no concern of cold ischemic time on the kidney allograft, hence full serological, NAT, and HBV DNA will be done on both the donor and the recipient. This should be followed with NA treatment until the HBV DNA level is undetected if it was high initially
The following condition must be met:
3) Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
This donor has an active infection with possible ongoing replication of HBV because of positive HBeAg. However, acute infection is usually diagnosed by positive HBsAg, clinical symptoms, and high aminotransferase of more than x 3 upper normal level
No, it will change.
4) What is your differential diagnosis
5) How would you manage this case?
References
Remember HBcAg is only in the hepatocyte.
HBeAg means viral replication so this is a highly infective situation confirmed by a PCR, to be accepted in EMERGENCY situation after counselling.
Thank you Prof Dawlat
Only in emergencies could a kidney from a HbsAg-positive donor be transplanted into an HBV-negative recipient.
HBsAg-positive allografts in HBsAg-negative recipients have a high risk of de novo infection. Most transplant hospitals do not transfer kidneys from HBsAg-positive donors, and in most countries, these donors may only be transplanted into matched HBsAg-positive recipients.
Most studies have shown that transplanting HBsAg-positive kidneys to recipients with natural immunity is safe and reasonable.
In recent research, we reported 5 successful kidney transplantations from HBsAg-positive donors to HBsAg-positive recipients with no post-transplant transaminase increase and a considerable decrease in waiting time.
Only in emergencies could a kidney from a HbsAg-positive donor be transplanted into an HBV-negative recipient.
Yes, First the donor should have HBV DNA to check the viremia, if it is positive, better to treat the donor before the donation
If HBV DNA is negative, the kidney can be given to an immune recipient (natural or vaccinated.
Despite a greater occurrence of acute hepatitis, kidney transplant patients of HBsAg-positive, HBV-DNA positive donors had comparable graft and patient survival, acute rejection, and post-transplant sequelae to those of HBsAg-negative kidneys.
These investigations showed that protective HBV immunity from past infection or immunization prevents chronic HBV infection in HBsAg-positive kidney recipients.
HBsAg-positive kidneys transplanted into HBV-naïve recipients may cause primary infection, although NA antivirals (entecavir and tenofovir) may suppress HBV long-term and avoid cirrhosis and liver failure. Hepatocellular carcinoma risk remains increased for these people.
The donor has active HBV infection, the same acceptance rules
Only in emergencies could a kidney from a HbsAg-positive donor be transplanted into an HBV-negative recipient. If the recipient accepts the risk:
The recipient should be treated with HBIg and NA directly post-transplantation.
chronic infected HBV
Results can be falsely positive for HBsAg
Infection with hepatitis D and hepatitis B viruses may occur simultaneously.
Take care of it with the help of a hepatology consultation.
counseling the recipient of the possibility of HBsAg-positive organs
A pre-transplant vaccine booster should be administered
Continue with the transplanting procedure.
start lamivudine or entecavir directly
close monitoring of HBV DNA and LFT post-transplantation.
References:
Veroux, M., Ardita, V., Corona, D., Giaquinta, A., Ekser, B., Sinagra, N., … & Veroux, P. (2016). Kidney transplantation from donors with hepatitis B. Medical Science Monitor: International Medical Journal of Experimental and Clinical Research, 22, 1427.
– British Transplantation Society Guidelines2018
Thankyou well done.
Remember HDV does not occur alone ,but usually with HBV.
-Will you accept this DBD donor?
-Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
-Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
-What is your differential diagnosis?
-How would you manage this case?
Source: BTS guidelines 2018
You correctly mentioned that in a DD you usually have no times for the rest of useful investigation but it is always wise is to store blood samples from the donor.
HB e AG means active viral replication,so you should take it from there.
Thank you prof for useful comments
The donor is HBsAg positive, HBsAb negative, HBcAb negative, both HBeAg and HBeAb are negative
The donor should undergo HDV Ab serology and HBV DNA levels.
Before we accept the HBsAg positive donor, we need to know the immune status of the recipient.
“Transplantation of a non-liver solid organ from an HBsAg positive donor to a non-immune recipient will result in chronic infection of the recipient.
In this setting, antivirals should be given to prevent HBV-related liver damage.”
HBV Vaccination
Monitoring for HBV Recurrence or De Novo Infection
If HBeAg and HBeAb are positive in addition to positive HBsAg, then its active hepatitis B infection, which needs to be treated before transplanted.
McPherson S, Elsharkawy AM, Ankcorn M, Ijaz S, Powell J, Rowe I, Tedder R, Andrews PA. Summary of the British Transplantation Society UK guidelines for hepatitis E and solid organ transplantation. Transplantation. 2018 Jan
Typing whole sentence in bold amounts to shouting.
I like your well structured detailed summary.
I appreciate level of recommendation in relation to each advice in relation to the type of disease and corresponding treatment.
Interpretation of current case; according virology report;
-HBsAg (positive) , HBsAb (negative) , HBcAb (negative)
-HBeAg (negative) , HBeAb (negative)
-HCV (negative) , HIV (negative)
-Considering this patient (non-immune chronically infected HBV)
and need further investigations (LFTs,HBV PCR,HDV&HEV serology,U/S Liver)
1-Will you accept this DBD donor?
Yes; I will accept this donor (after informed consent of high risk for transmission of infection)
According to British Transplantation Society Guidelines:March 2018;
-If need demands, the non-liver solid organs of the HBsAg positive organ donor can be used for any recipient, after an individualised assessment of risk and benefit. (2C)
-Individuals undergoing non-liver solid organ transplantation who are HBsAg positive must have liver disease staging and suppression of HBV DNA by either tenofovir or entecavir before transplantation if there is a standard clinical indication. (1B)
2-Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
Yes; I will accept if HBs positive Doner to HBsAg positive recipient;
According to British Transplantation Society Guidelines:March 2018;
-Individuals undergoing non-liver solid organ transplantation who are HBsAg positive must have liver disease staging and suppression of HBV DNA by either tenofovir or entecavir before transplantation if there is a standard clinical indication. (1B)
-HBsAg positive donors should not be used for HBV/HDV co-infected recipients. (1C)
3-Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
Yes; management will be changed; because this high risk for HBV recurrence.
(HBeAg) and (anti-HBe or HBeAb);
-Useful in monitoring chronic HBV infection, especially during antiviral therapy.
-The presence of HBeAg relates to viral replication.
-Patients with HBeAg are generally considered to be more infectious than those with anti-HBe and without HBeAg.
According to British Transplantation Society Guidelines:March 2018;
-Life-long combination therapy with HBIG and a potent NA can potentially be given to patients who were traditionally considered at high risk for HBV recurrence. (2B)
–Individuals with decompensated cirrhosis and detectable HBV DNA require urgent antiviral treatment with NA(s). Entecavir and tenofovir are the first line antiviral agents and should be continued indefinitely. (1A)
-Individuals with decompensated cirrhosis due to hepatitis B should be treated in specialist liver units as the application of antiviral therapy is complex and these patients may be candidates for liver transplantation. (1C)
-Patients with advanced HBV-related liver disease requiring another organ transplant be considered for combined transplantation after careful consideration of the potential risks and benefits. (2C)
4-What is your differential diagnosis?
Considered at high risk for HBV recurrence;
-HBeAg positive patients,
-HBV DNA positive at time of transplant,
-Those transplanted for hepatocellular carcinoma or,
-Those who are HIV co-infected.
5-How would you manage this case?
According to British Transplantation Society Guidelines:March 2018;
-In HBsAg positive individuals deemed to be at high risk of recurrence, combination therapy with HBIg and/or a potent NA is recommended from the time of transplantation to prevent HBV reinfection post-liver transplant. (1B)
-Individuals with fulminant liver failure associated with hepatitis B infection must be managed in a specialist liver centre. (1C)
-HBV/HDV recipients should receive combination HBIg/NA prophylaxis from time of transplantation. (1C)
-For HBV/HDV infected recipients HBIg withdrawal from combination HBIg/nucleo(t)side analogues(NA) prophylaxis can be considered, but not within 12 months of transplantation. (2C)
-HBV DNA and HBsAg should be monitored every three months in the first year and thereafter every six months in HBsAg positive liver transplant recipients or individuals receiving a graft from a HBcAb positive donor, regardless of treatment or prophylaxis regimen. (1C)
-Amongst renal transplant recipients who are HBcAb positive, if HBsAb are < 100 IU/mL, then vaccination should be considered to boost the protective titre of HBsAb and minimise the risk of reactivation. (2C)
-In those who fail to respond to the initial HBV vaccination schedule, a second series should be administered. (2C)
References; British Transplantation Society Guidelines:March 2018;
I like your well structured detailed summary.
I appreciate level of recommendation in relation to each advice in relation to the type of disease and corresponding treatment.
· Will you accept this DBD donor?
Yes but depending on recipient HBV status;
· If recipient is vaccinated with anti HBs titer is more than 10 mIU/ml.
· Had chronic infection in past with lifelong antiviral therapy.
· Prior infection and immunity with antiviral therapy during intense IS.
NO if no immunity or not vaccinated, would need immunoglobulin’s and antiviral therapy if transplant occurred. HBV DNA, HBsAg and anti HBc should be checke every 3 months
· Will you accept this donor as a live donor if the recipient is also HBsAg positive? If yes, what are the conditions that should be met?
Yes but would need lifelong antiviral therapy if the recipient is established chronic infection, to do so will have to do Anti HBs, Ant HBc antibodies and DNA PCR.
In case of live donor HBV negative recipient should be vaccinated prior to transplantation. HBV DNA, HBsAg and anti HBc should be checke every 3 months
· Assume both HBeAg and HBeAb are positive in addition to positive HBsAg. Will this change your management?
No will manage on the same line.
· How would you manage this case?
· Recipient is immunized by vaccination than measure titer prior to transplantation if titer is less than 100mIU/ml than may consider immunoglobulin and antiviral therapy for upto 1 year.
· Recipient who had prior infection need to have antiviral indefinitely.
· No immunity to HBV or no previous exposure of recipient ideally avoids graft from HBsAg positive (chronic infection) donors. But if occurred (compelling reasons) than immunoglobulin with antiviral and vaccination. Though response to vaccination in recipients who are on maintenance Immunosuppressant is poor.
References UpToDate
I appreciate your careful well balanced clinical approach in managing this patient that is well supported by evidence.
Will do HBV DNA
Yes
Provided Anti- Hbs = or > 10 IU/L in the receipient
No
If Anti- Hbs < 10 IU/L in the receipient
Will accept along with 12 months of nucleotide antiviral prophylaxis along with HBIG when receipient is Naïve or Anti- Hbs < 10 IU/L only if urgent need for KT (exhausted multiple vascular access,with ongoing uremia despite adequate hemodialysis prescription).
Yes will accept as donor provided,
Receipient should have –
no abnormalities of liver function test
no history of liver disease within the previous 28 days
who are not living in the area of possible mutation strain of HBV
result of liver biopsy that did not show evidence of cirrhosis.
received antiviral treatment
Will discard the organ .
There may be instances where HBsAg may be momentarily positive within 30 days of receiving a dose of the hepatitis B vaccine.
HBV DNA needs to be done to rule out infection.
In the index case HBsAg positive, HBsAb negative, HBcAb negative, both HBeAg and HBeAb are negative.So recent vaccination with Hep B vaccine needs to be asked for.
Other possibility is wrong report.
Interpretation of hepatitis B serology report-
HBsAg—Positive
Total anti-HBc — Positive
IgM anti-HBc — Positive
Anti-HBs — Negative
Then Acute infection
HBsAg — Positive
Total anti-HBc — Positive
IgM anti-HBc — Negative
Anti-HBs — Negative
Then Chronic Infection
HBsAg — Negative
Total anti-HBc — Positive
Anti-HBs — Positive
Then Resolved Infection
HBsAg — Negative
Total anti-HBc — Negative
Anti-HBs — Positive
Immune from receipt of prior vaccination (if documented complete series)
HBsAg — Negative
Total anti-HBc — Positive
Anti-HBs — Negative
So when Only core antibody is positive, then
Resolved infection where anti-HBs levels have waned
Occult Infection
Passive transfer of anti-HBc to an infant born to an HBsAg-positive gestational parent
A false positive, thus patient is susceptible
A mutant HBsAg strain that is not detectable by laboratory assay
HBsAg — Negative
Total anti-HBc — Negative
Anti-HBs — Negative
Then Susceptible, never infected (if no documentation of HepB vaccine series completion)
monitoring liver enzymes, HBsAg, and HBV DNA every 3 months for at least 12 months post-transplantation and then yearly.
monitoring of anti-HBs concentration should be done at least
yearly.
If Anti HBs (<10 mIU/mL) a total complete course of vaccination with a follow-up level at 4-wk after a complete course of treatment.
Anti HBs (+ or > 10 mIU/mL) ,then lamivudine or entecavir for 12 months post transplantation .
Anti HBs (> 100 mIU/mL),then lamivudine or entecavir for 6 months post transplantation .
Anti HBs (> 10 mIU/mL) and positive recipients can receive kidney transplants from anti-HBc (+) donors without a need for prophylaxis antiviral medications due to the negligible risk of HBV transmission.
In contrast, naïve recipients who received kidneys from anti-HBc (+) donors should receive lamivudine prophylaxis without HBIG for at least 1 year.
In the setting of HBs Ag (+) donors, recipients with protective anti-HBs (> 10 mIU/mL) were considered suitable to receive the allocation of kidney grafts.
Further risk should be assessed by the result of the NAT test and HBV DNA measurement. If the result of nucleic acid for HBV was negative and HBV DNA was undetectable no NA prophylaxis (in the setting of no potent induction therapy), or prescription of NA alone without HBIG.
If the anti-HBs is > 100 mIU/mL, one can proceed to KT without
NA prophylaxis.
The first donor group is the anti-HBc positive group in which the rate of transmission appears to be negligible according to the recipient’s
protective immunity status. The overall seroconversion rate was 3.24%.
The second donor group is the HBsAg positive group where the HBV transmission remains a challenging problem.
Kidney transplant from donors with hepatitis B: A challenging
treatment option
Praopilad Srisuwarn et al
algorithm
Thank you Dr Prakash for such great answer but few comments need clarification:
1- Do you think you need to check the donor for HDV as well?
2-When you quote a reference please put the complete reference not as you mentioned Praopilad Srisuwarn et al
3- The diagram you quoted is interesting where it mandated check of HDV DNA which you did not mention in details in your answer