3. You were offered kidneys from a 59-year-old male DBD (donor after brain stem death) donor who suffered from SAH (grade 5) complicating cerebral aneurysm. His retrieval S Cr was 72 µmol/L. Virology was reported as follows: HBsAg negative, HBsAb negative, HBcAb positive, and both HBeAg and HBeAb are negative. Both HCV and HIV are negative.
There is sufficient evidence to provide confidence that nearly all solid organs from donors who are core antibody positive, whether HBsAg is negative or positive, can and should be used for transplantation.
Donation of non-liver solid organs from the core antibody positive donor is rarely associated with de novo infection of the recipient.
When a HBcAb positive donor is used, lamivudine prophylaxis may be given for six months after transplantation, although the risk of transmission is very low.
will l you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
Yes.
HBsAg and antibodies should be checked. also HDV for both ,Liver function test and abdominal ultrasound for both.
Antiviral should be give posttransplant.
References:
1- BTS ,Guidelines for Hepatitis B & Solid Organ Transplantation, 2018.
This donor can be gladly accepted as the core antibody when only positive while other HBV antibody screening are negative, it is then indicative of proper immune system which succeeded to eliminate this infection.
Considering the recipient status HBcAb positivity, further HBV profile screening is required.
HBV nucleic acid assessment by PCR, besides HDV to rule our HDV co-infection.
Other hepatropic 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 LFTs, 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.
Can this DBD be accepted? The donor is a donor after brain death with good renal function….The donor is HBcAb positive…Other serological tests for Hepatitis B infection are negative….HbsAg, HbeAg HBeAb and HIV,HCV are negative….Positive Anti HBcAb signifies either a past infection or a resolving infection…
As per the BTS guidelines, kidneys from HBcAb positive donors can be used for any recipients…The risk of de novo Hepatitis B infection in recipient is low….
As this is a cadaver renal donor we will be able to directly transplant the organ without evaluating the donor further….
The recipient should have finished primary immune – prophylaxis’s with Hepatitis B vacccine..If the recipient is immune (anti HBs titire >10 IU/ml), there is no need of anti viral prophylaxsis and regular monitoring of the HBV DNA viral load post transplant is indicated at 7 days, 14 days and 21 days and monthly for 3 months…If the recipient is not vaccinated and is not immune (anti HBs titre <10 mIU/ml), the recipient has to be treated with anti virals namely lamividine or tenofovir for 6months after transplant
If this was a live donor renal transplant?
A HBcAb positive live donor can be accepted for a recipient who is HBcAb positive…the donor and the recipient have to be evaluated in detail….it is important to do a detailed evaluation for the donor…the donor should be screened to rule out cirrhosis of the liver HBV DNA testing of the donor is needed, so as OGD, fibroscan of the donor it could be a past infection with underlying cirrhosis.
The recipient is also core antibody positive indicating past infection of chronic Hepatitis B infection….other markers like HbsAg, anti HBsAg, HBeAg and HBV DNA should be done…HDV RNA PCR to rule out co infection should also b done…We should do LFT , PT INR of the recipient with OGD and fibroscan of the liver to rule of fibrosis…. If cirrhosis is ruled out we can proceed for renal transplant alone…If the recipient is HBcAB positive and Anti Hbs Titre < 100 IU/ml, vaccination should be considered for the recipient o boost the titres….the AST recommends no need prophylaxis with antivirals for those vaccinated with HBV vaccine and good anti HBs titre….
If the recipient is highly immunosuppressed then anti viral prophylaxis’s is indicated if the use of ATG, Plasma and rituximab, or of rising serial titres of HBV DNA after transplant is demonstrated…
● Will you accept this DBD donor?
☆ Yes . I will accept him .
☆ Solid organ transplant recipients of HBcAb-positive organ donors, exposed to immunosuppression, may have a higher risk of developing de novo HBV infection after transplantation.But it’s impact in renal transplantation appears low to negligible.
☆ The risk may be more accurately determined by measuring HBV-DNA than HBcAb, HBcAb-positive HBV-DNA negative donors are unlikely to transmit infection to recipients.
● Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
☆ In the context of living donation, donors who are HBcAb alone (with negative HBsAg and undetectable DNA in blood) can therefore donate. The prospective recipient will ideally have been effectively immunised against HBV,
☆ Although immunization can be repeated post-transplant if a suboptimal antibody
response has been made. The addition of anti-viral drugs may be considered, especially in recipients with a low HBsAb response to vaccination.
☆ Strict surveillance serologies are mandatory and an HBIg single-shot prophylaxis may reduce the risk of HBV seroconversion or reactivation in all naïve or HBcAb-positive transplant recipients.
References:
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: Yes, I would accept conditions with isolated HBC AB positivity includes: previous infection (if HBC AB IgG is positive), window phase (if HBC AB IgM is positive), occult infection (if HBC DNA is positive), or passive transfer of this Ab by transfusion. Hence, a history of transfusion, IV abuse, previous hepatitis B, or exposure to it, should be taken after TX, prophylaxis is necessary and associated with close monitoring.
Q2: for live donation, more investigations are needed before transplantation such as HBV DNA, in both recipient and donor. In addition, HBC Ab in recipients with HBV DNA simultaneously shows the carrier state of the recipient and needs lifelong prophylaxis with entecavir or tenofovir alafenamide.
Reference:
Malinis, M., & Boucher, H. W. (2019). Screening of donor and candidate prior to solid organ transplantation—Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clinical Transplantation, 33(9). https://doi.org/10.1111/ctr.13548
Will you accept this DBD donor? · I will accept this DBD donor asthe risk of de novo HBV infection is low. The BTS guidelines stated that kidneys from HBcAb positive donors can be used for any recipient. However, a heptologist should be involved as part of the MDT and during the follow-up and the recipient should receive proper counselling.
· Administration of Lamivudine prophylaxis to the recipient depends on the recipient HBV immune status. If the recipient is HBV immune (anti-HBs +), no need for prophylaxis. Otherwise, administer 6 months Lamivudine prophylaxis.
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
· Yes. HBcAb + live donor can be accepted for HBcAb+ recipient.
· The donor should be assessed by:
· Liver function tests
· Check the type of HBcAb (IgG or IgM)
· HBV-DNA to exclude occult HBV infection
· Abdominal US
· The recipient should be assessed by: checking other serological markers including HBsAg, HBsAb, HBeAg, HBeAb, and HBV DNA by PCR as well as HDV to rule our HDV co-infection.
· Antiviral prophylaxis with tenofovir or entecavir can be given as this recipient is only HBcAb positive.
· Regular post-transplant monitoring of LFTs, HBsAg and HBV DNA should be done every 3 months in year 1 and during periods of intense immunosuppression.
References:
1. Ouseph R, Eng M, Ravindra K, Brock GN, Buell JF, Marvin MR. Review of the use of hepatitis B core antibody-positive kidney donors. Transplant Rev (Orlando). 2010 Oct; 24(4):167-71.
2. Guidelines for Hepatitis B & Solid Organ Transplantation. British Transplantation Society Guidelines, 2018.
Regarding his virology profile yes, I will accept him . after satisfying routine immune matching.
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
According to current guidelines, there is an increasing trend of accepting non-liver organs from total hepatitis B core antibody-positive [anti-HBc (+)] donors to be used in any recipient regardless of HBV immune status without prophylaxis due to the negligible risk of de novo infection. Although some studies mentioned that despite the low risk of transmission is very low, lamivudine prophylaxis may be given for 6 months after transplantation, when a HBcAb positive donor is used.
In acute hepatitis B infection, immunoglobulin M (IgM) antibody to hepatitis B core antigen (IgM anti-HBc) becomes positive after 4 wk to 6 wk of exposure indicating recent infection and active viral replication whereas total hepatitis B core antibody (anti-HBc) appear at the onset of symptoms and persists for life.
In clinical practice, isolated anti-HBc is commonly observed. This may occur in several clinical settings. First, the early window period of acute hepatitis B. Second, a resolved HBV infection with waning of anti-HBs titer. Third, a false positive anti-HBc. This setting is commonly found in an area with a low prevalence of HBV infection. Fourth, an occult chronic HBV infection with low viremia and undetectable HBsAg. The latter can occur with a poor test quality or when there is a mutation of HBsAg
Condition that should be met. –full virology profile for recipient ,If recipient HBsAg & HBV DNA is negative then vaccination of the recipient. – Monitoring for HBV Infection; HBV DNA and HBsAg should be monitored every 3 months in the first yearreference Praopilad Srisuwarn and Vasant Sumethkul .Kidney transplant from donors with hepatitis B: A challenging treatment optionWorld J Hepatol. 2021 Aug 27; 13(8): 853–867
will you accept this DBD donor?
I will accept the donor
ill you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
yes i will accept as the risk of deactivation is low
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
yes,I will accept ,but there is risk of reactivation of virus. Recipient HbsAg status should be checked.,Because in case of HbsAg positive risk of reactivation is highest.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. Among HBsAg-negative patients, reactivation is defined by the appearance of HBV DNA or the reappearance of HBsAg.Prior infection(Anti HBc antibody positive) is not a containdication to transplantation.Recipients who are anti-HBc positive have evidence of prior infection and need antiviral therapy to prevent HBV reactivation secondary to immunosuppressive therapy. The presence of anti-HBs at time of transplantation may not prevent reactivation, because anti-HBs titer can decrease and become undetectable with immunosuppression.The duration of antiviral therapy can vary. Some centers administer antiviral therapy indefinitely to all recipients with prior HBV. Others discontinue treatment when immunosuppression is reduced to low-dose maintenance level and monitor closely thereafter, unless the patient is receiving immunosuppression with an agent associated with a high risk of HBV reactivation (eg, rituximab).
Monitoring/management of reactivation
What to monitor – The approach to monitoring for HBV reactivation or flare depends upon whether the recipient is receiving preventive antiviral therapy and/or the type of immunosuppressive regimen that is used:
Recipients on antiviral therapy – Recipients receiving antiviral therapy to prevent reactivation or flare should have serum aminotransferases and HBV DNA monitored every six months or more frequently as indicated.
If antiviral therapy is discontinued, we monitor liver chemistries, HBV DNA, and HBsAg at least once every three months for at least one year.If reactivation occurs, patients should resume antiviral therapy
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
Yes i accept this donor as a live donor.
If the recipient HBsAg negative but Anti HBs positive then risk of HBV reactivation is low to moderate. But the risk is moderate to high if the recipient HBsAg & Anti HBs both are negative. The risk is very high if recipient’s HBsAg positive.
Condition that should be met:
– Detail virological study of the recipient.
– If recipient HBsAg, HBeAg & HBV DNA is negative then vaccination of the recipient.
– Target antiviral treatment & prophylaxis should be given according to HBV status
Yes , I would receive this patient . Patient without serology indicative of replication, so this result represents a criterion for curing the disease.
To prove that there is no replication, HBV DNA PCR could be used.
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
Yes, but the recipient should be further evaluated for the existence of liver disease at this time and monitored every 3 months with the test of HBsAg and HBV DNA for at least 1year post-transplant. In addition to performing prophylaxis treatment with entecavir or tenofovir
Yes, I will accept this donor if no other choice are available, but the recipient should be vaccinated and maintained on antiviral therapy for 6 months with regular follow up for graft function and HBV DNA PCR .
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
Yes I will accept this donation but first we must assess both the donor and recipient by doing HBV DNA PCR, HBsAg , anti-HBc IgM &IgG, HDV serology , Abdominal US, LFT, and we need to check anti-HBC level in recipient if less than 100 we must give vaccination and HB IG with antiviral prophylaxis for 6 months.
Reference
BTS guidelines 2017.
Will you accept this donor? Yes, kidneys from a HBcAb positive organ donor can be safely used, as the risk of HBV transmission is low. · Anti-HbcAb is positive if the patient has resolved or resolving hepatitis B infection, or during window phase in which HbsAg is not detectable – HBV DNA PCR can detect occult infection · The recipient should have been vaccinated with HBV. · Recipient should be explained about need monitoring or antiviral prophylaxis after transplant for at least 06mths.
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met–
Anti-HBcAb positive live donor can also be accepted – unless there is a positive HBcAb-IgM or positive HBV DNA Further investigations like HBV DNA PCR, anti-HbcIg M and IgG, LFT, USG abdomen, HDV serology of both donor and recipient should be done. – Recipient’s anti-Hbs Ab needs to be tested – if <10 IU/ml, restart HBV vaccine 4 doses – Recipient should receive antiviral prophylaxis with either entecavir or tenofovir – close monitoring of graft function and regular test of HBsAg and HBV DNA every 3 months for at least 1year post-transplant. 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. Int med journal of experimental and clinical research. 2016 Apr 28; 22: 1427-34. PMID: 27123988. Pubmed Central PMCID: PMC4915324. Epub 2016/04/29. eng.
3. Srisuwarn P, Sumethkul V. Kidney transplant from donors with hepatitis B: A challenging treatment option. World J Hepatol 2021 Aug 27; 13(8): 853-67. PubMed PMID: 34552692. Pubmed Central PMCID: PMC8422915. Epub 2021/09/24. eng. 4. 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 May; 15(5): 1162-72. PubMed PMID: 25707744. Epub 2015/02/25. eng
Yes, I will accept this living donor with anti HBc Ab. Those patients who are Anti-HBc antibody positive and HBsAg negative should not be excluded from transplantation. Those patients who are Anti-HBc antibody positive and HBsAg negative should not receive antiviral prophylaxis as the risk of reactivation is low. Patients who are Anti-HBc antibody positive and HBsAg negative should be monitored for a minimum of one year post transplantation by monitoring of HBsAg and HBV DNA. If the donor has chronic Hep B infection, then the recipient should receive prophylaxis with lamuvidin for 1 year.
Will you accept this DBD donor?
Anti-Hbc positivity means either the patient has resolved or resolving hepatitis B infection,or the patient has False-positive anti-HBc, or the patient is in window phase in which HbsAg is not detectable and PCR for HBV DNA to be done to check for acute infection
Yes, this donor can be accepted if no other donor available but the recipient should be vaccinated and placed on antiviral prophylaxis after transplant for at least 06mths and all risks explained to the recipient. Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met–
In this case, donation can be accepted but before that investigations like PCR for HBV DNA , anti-HbcIg M and IgG, LFTs ,USG abdomen ,HDV serology of both donor and recipient should be done. Anti-Hbs of the recipient should also be done. Recipient should be vaccinated if anti-Hbs titer less than 100 and also placed on antiviral prophylaxis post-transplant with close monitoring of graft function and regular test of HBsAg and HBV DNA 3 monthly for at least 1 year post-transplant.
REFERENCES:
1- British Transplantation Society Guidelines: Guidelines for Hepatitis B & Solid Organ Transplantation 2018
The patient received DBD from an HBcAb positive Donor.
Where donor is HBcAb positive. Other serological tests (HBsAag, HBeAg, HBeAb, HIV and HCV) are negative.
HBcAb results from resolving infection or a low level of chronic infection.
I shall accept this donor as risk of transmission is low
The decision of using antiviral prophylaxis is according to the immunity status of the recipient
If HBsAg is positive (immunized recipient) then no need for antiviral
If negative then we shall use antiviral e.g Lamivudine for 6 months
In case of isolated HBcAb then we shall do PCR test to detect viral load
As well as liver function tests and Ultrasound liver.
Recipient should be detected for HBV markers and liver function tests.
And check the vaccination status if below the 100 IU per ml then a booster dose should be indicated.
In our case donor Has HBcAb positive and also HBcAb is positive in recipient
So antiviral prophylaxis would be required.
In addition to vaccination of the recipient and consulting a hepatologist.
And regular check for HBV PCR as well as liver function tests and Ultrasound.
Yes, I will accept this living donor with anti HBc Ab. Those patients who are Anti-HBc antibody positive and HBsAg negative should not be excluded from transplantation. Those patients who are Anti-HBc antibody positive and HBsAg negative should not receive antiviral prophylaxis as the risk of reactivation is low. Patients who are Anti-HBc antibody positive and HBsAg negative should be monitored for a minimum of one year post transplantation by monitoring of HBsAg and HBV DNA. If the donor has chronic Hep B infection, then the recipient should receive prophylaxis with lamuvidin for 1 year.
– kidneys from a HBcAb positive organ donor can be used on any recipient since the risk of de novo HBV infection is low so is the risk of HBV transmission
– unless there is a positive HBcAb IgM or positive HBV DNA
– however, the recipient should receive antiviral prophylaxis with either entecavir or tenofovir
– HBIG can be considered if there is no response to antiviral therapy
References
1. Veroux M, Ardita V, Corona D, Giaquinta A, Ekser B, Sinagra N, et al. Kidney Transplantation From Donors with Hepatitis B. Medical science monitor : international medical journal of experimental and clinical research. 2016 Apr 28;22:1427-34. PubMed PMID: 27123988. Pubmed Central PMCID: PMC4915324. Epub 2016/04/29. eng.
2. 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.
3. 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
This is BDD with past history of HepB infection denoting ANTHBC Ab positive, which is indicating to the past infection and formation of immunity and this is according to the BTS having a high risk of reactivation or Denovo HBV infection. Accordingly, I am going to accept this donor with close observation of the HBV PCR level adding to that. He is a candidate for lamivudine for 6 months post-RTX.
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
Yes,I will accept especially if the HBV DNA is negative with a close follow up and observation
DBD with this serology suggest PAST INFECTION with HBV
We can accept kidney with possibility of reactivation of this infection in recipient depending on his/her serology of HBV as follow
LOW RISH – NEGATIVE SEROLOGY
HIGH RISK- SEROLOGY SUGGESTIVE OF PAST INFECTION like CORE ANTIBODY
VERY HIGH RISK- ACTIVE OR RECENT INFECTION SEROLOGY LIKE HBsAG and HBeAG OR AB positive
This DBD donor has anti-HBc Ab positive with negative HBsAg denoting past infection.
. Potential donor with positive HBcAb and negative HBsAg can be accepted for any recipient with low risk regarding de novo HBV infection. Donor can accepted with 6 months of lamuvidin for prophylaxis post transplantation.
In case the donor is a live :
It depends on HBV immune status of the recipient to explore risk of transmission or reactivation of the viral B infection.
HBsAg-ve/ HBsAb-ve denotes low to moderate risk
Hb cAb positive and HbsAb -ve denote moderate to high risk.
HBsAg+ve/ HbcAb+ve denotes very high risk
Donor HBV DNA quantification is needed to rule out occult infection.
Live donor can be accepted with excluding of occult infection in donor in low risk recipient Reference:
BTS guidelines for Hepatitis B & Solid Organ Transplantation,2018.
· Will you accept this DBD donor?
These donors have been exposed to hepatitis B in the past but test negative for the more serious hepatitis B surface antigen. In clinical practice, isolated anti-HBc is commonly observed. This may occur in several clinical settings. First, the early window period of acute hepatitis B. Second, a resolved HBV infection with waning of anti-HBs titer. Third, a false positive anti-HBc antibodies.
According to current guidelines, there is an increasing trend of accepting non-liver organs from total hepatitis B core antibody-positive [anti-HBc (+)] donors to be used in any recipient regardless of HBV immune status without prophylaxis due to the negligible risk of de novo infection. Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met? · Yes, especially if recipient has good antibody titer and negative HBV DNA.
· References: 1-World J Hepatol.2017 Sep 8; 9(25): 1054–1063. Published online 2017 Sep 8
Since he is a deceased donor and there will be a need for triple immunosuppression, including corticosteroids, he would proceed with prophylaxis for twelve months with Tenofovir alafenamide (TAF) or Entecavir.
This DBD donor may be accepted for renal transplantation.
Since HBsAg, HBsAb, HBeAg, HBeAb, HIV and HCV all are negative and the donor is HBcAb positive, it interprets to either a resolving acute infection (where Anti HBc IgM is positive), or a resolved HBV infection (where Anti HBc IgG is positive), or a low level chronic infection (where HBV DNA by PCR is positive).
Since the infection is resolving or has resolved or is a low grade infection, the risk of de novo HBV infection is low and prophylaxis with Lamivudine for 6 months post-transplant may be given to the recipient if the recipient has low Anti-HBs Ab titres. If the recipient has is HBV immune and has Anti-HBs Ab titres > 100 IU/L, then there is no need of antiviral prophylaxis. Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met? Yes, this live donor may be accepted for renal transplantation to a HBcAb positive recipient, provided the following conditions are met. Conditions for Donor:
Liver function tests have to be within normal limits and coarse hepatic parenchyma is to be excluded on abdominal ultrasound.
Anti-HBc IgG and IgM should be tested. Donor cannot be IgM positive.
HBV DNA by PCR testing of the donor should be done (to exclude occult HBV infection).
Conditions for Recipient:
HBsAg should be negative, HBsAb should be >100 IU/ml
HBeAg should be negative, should be positive and HBV DNA PCR should be negative. HBeAb should be done.
If Anti-HBcAb is positive and Anti-HBsAb is <100 IU/ml, boostervaccination should be given to the recipient.
In conclusion, the recipient cannot be transplanted during the period of active hepatitis infection. He may undergo transplantation if he is currently immune due to a past acute infection. He may also get transplanted with prophylactic measures, if he has a low level chronic infection with adequate counselling regarding risks of acute flares during immunosuppression. References: British Transplantation Society. Guidelines for Hepatitis B and Solid Organ Transplantation, 1st ed.; British Transplantation Society: Macclesfield, UK, 2018 Ouseph R, Eng M, Ravindra K, Brock GN, Buell JF, Marvin MR. Review of the use of hepatitis B core antibody-positive kidney donors. Transplant Rev (Orlando). 2010 Oct;24(4):167-71. doi: 10.1016/j.trre.2010.05.001. Epub 2010 Jul 23. PMID: 20655722.
Will you accept this DBD donor?
this patient offered graft from DBD and his virology screening showed HBcAb positive so further assessment should be done as HBcAb maybe related to old resolved infection or recent infection in window phase HBV PCR should be done if negative it means old resolved infection, if positive it means recent infection in window phase. HDV PCR also is needed and if positive organ better to discarded.
according to British society of organ transplantation organ of HBVcAb positive donor can be retrieved as kidney is like liver and not exposed to latent HBV infection So, I will accept this potential donor but recipient immune state is important to decide the need for antiviral prophylactic if the antibodies titter more than 100iu/ml so no need for antiviral prophylactic but if below 10iu/ml so antiviral prophylactic for 6m is needed.
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met? two main differences in the scenario 1-donor is alive so if HBV PCR positive he is exposed to complication including GN and donation should be delayed until proper treatment with sustained viral response then he should be reevaluated for donation. 2-reicient is also HBcAb positive so he is natural immune with risk of reactivation if the patient planned to receive heavy induction or desensitization so prophylactic treatment should be given. References:
Ouseph R, Eng M, Ravindra K, Brock GN, Buell JF, Marvin MR. Review of the use of hepatitis B core antibody-positive kidney donors. Transplant Rev (Orlando). 2010 Oct;24(4):167-71. doi: 10.1016/j.trre.2010.05.001. Epub 2010 Jul 23. PMID: 20655722.
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.
There are a substantial number of reports of kidneys transplanted from HBsAg negative/DNA undetectable, HBcAb positive deceased donors in which there have been a low risk of HBV seroconversion and no excess risk of graft failure or shortterm morbidity .
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
Yes,,,,
All prospective living donors should be tested for both Hepatitis B surface antigen (HBsAg) and Hepatitis B core antibody (HBcAb). If the HBcAb is positive, the donor should be tested for the presence of HBV DNA and Hepatitis B surface antibody (HBsAb). If HBsAb is >100 iU/L and HBV DNA is not detected, the infectious risk of the donor is low.
Living donors who are HBcAb alone with negative HBsAg and undetectable DNA in blood) can therefore donate. The prospective recipient will ideally have been effectively immunised against HBV, although immunization can be repeated post-transplant if a suboptimal antibody response has been made. The addition of anti-viral drugs may be considered, especially in recipients with a low HBsAb response to vaccination. Under these circumstances, advice from specialists with appropriate expertise should be sought and the donor and recipient should be fully informed.
When a HBcAb positive donor is used, lamivudine prophylaxis may be given for six months after transplantation, although the risk of transmission is very low.
Any potential transplant recipients found to be HBcAb positive but HBsAg negative (past infection) must have HBV DNA and HDV serology testing to exclude occult HBV or HDV infection.
All donors who are positive for HBcAb but HBsAg negative (past HBV exposure) must have HBV DNA testing to exclude the possibility of occult HBV infection.
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.
All prospective solid organ transplant recipients should receive a high-dose, accelerated vaccine schedule.
In those who fail to respond to the initial HBV vaccination schedule, a second series should be administered.
DD with anti-HBC positive (prior infection) the risk of transmission is negligible unless the donor is HBV DNA positive, in which case prophylactic antiviral therapy is recommended for one year, including entecavir and tenofovir
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
hepatitis BcAb in both donor and recipient means prior infection .recipient who has anti-HBc positive, HBV reactivation may occur secondary to immunosuppression therapy.
the presence of antiHBs at the time of Transplant may not prevent reactivation because anti -HBs titer can decrease and become undetectable with IS.
duration varies some give antiviral therapy indefinitely to all recipients with prior HBV.
others discontinue treatment when IS is reduced to a low maintenance level and monitor closely thereafter unless the patient receiving IS with an agent associated with a high risk of HBV reactivation (e.g rituximab)
references
update
· Will you accept this DBD donor? Yes , I will as this donor has excellent graft function and positive Anti HBV c Ab while all other serology negative corresponds with -Past HBV infection . -Occult HBV infection requiring further confirmation with HBV quantitative DNA PCR . – Assessment of risk of HBV infection in thisdonor is needed incuding history of previus blood transfusion . As the risk of acquiring HBV infection in HBs Ag –ve/ HBc Ab + ve donor ranges 0-5% ,so dueto shortage of donor pool , donors with previous HBV infection could be accepted. · Will you accept this donor as a live donor if the recipient is also HBcAb positive? Yes, I will · If yes, what are the conditions that should be met? – Assess risk of HBV reactivation depending on presence of positive HBs Ag , HBV DNA PCR . – Evaluate liver function to exclude decompensated LCF. – Exclude presence of other viral hepatitis as HEV , HDV. – Regularly monitor liver function to detect HBV reactivation early with HBs Ag and HBc Ab every 3 months and HBV DNA PCR every 6 months. – Start HBV treatment at time of transplantation with lamivudine ,entecavir or tenofovir. – Use the lowest possible dose of IS drugs needed to prevent rejection and try to early withdraw steroidtreatment or lower it to 5 mg daily. Ref: 1- Guidelines for Hepatitis B & Solid Organ Transplantation First Edition March 2018 .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 2- Fabrizio F, Bunnapradist S, Martin P. Transplanting kidneys from donors with prior hepatitis B infection: one response to the organ shortage. J Nephrol. 2002 Nov-Dec;15(6):605-13. PMID: 12495272.
Yes will accept this donors. Organs from anti-HBc+ donors should be considered for all adult transplant candidates after an individualized assessment of the risks and benefits and appropriate patient consent. Indefinite antiviral prophylaxis is recommended in liver recipients with no immunity or vaccine immunity but not in liver recipients with natural immunity. Antiviral prophylaxis may be considered for up to 1 year in susceptible non-liver recipients but is not recommended in immune non-liver recipients. Although no longer the treatment of choice in patients with chronic HBV, lamivudine remains the most cost-effective choice for prophylaxis in this setting.
3. You were offered kidneys from a 59-year-old male DBD (donor after brain stem death) donor who suffered from SAH (grade 5) complicating cerebral aneurysm. His retrieval S Cr was 72 µmol/L. Virology was reported as follows: HBsAg negative, HBsAb negative, HBcAb positive, and both HBeAg and HBeAb are negative. Both HCV and HIV are negative.
– yes, I would, due to the growing demand for organ donors this donor may still be a safe option
– a positive HBcAb result indicates a past or current infection
– HBcAb does not confer any protection against HBV
– since the donor was HBsAg negative and HBsAb negative, he could be infected, susceptible or have a resolved infection
– the kidneys from a HBcAb positive organ donor can be used on any recipient since the risk of de novo HBV infection is low
– however, the recipient should receive antiviral prophylaxis
– four possible interpretations for a state of isolated HBcAb (i.e., HBsAg negative, HBcAb positive, HBsAb negative): –
past exposure with resolved infection and immunity (most common)
no infection or immunity (false positive HBcAb)
occult chronic infection
past exposure with resolving acute infection
– presence of HBV DNA, HBsAg, HBeAg are markers of active infection
– IgM anti-HBc (IgM HBcAb) is a marker of acute or reactivated infection
– HBsAb is a marker of immunity
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met? (1-3)
Issues/ concerns
– living donor who is HBsAg negative, HBsAb negative, HBcAb positive, HBeAg negative, HBeAb negative, HCV negative, HIV negative
– recipient – HBcAb positive
– HBcAb positive is suggestive of prior infection
– the goal of care among recipients with prior or chronic HBV infection is to prevent HBV reactivation and worsening of liver disease
– generally, recipients with prior or chronic HBV infection can receive a kidney transplant from any donor regardless of the donor’s HBV status; however, they should be offered antiviral therapy to prevent reactivation which may occur secondary to immunosuppressive therapy
– for recipients with prior infection (HBsAg negative and HBcAb positive): – the preferred antiviral therapies include entecavir and tenofovir (preferably tenofovir alafenamide as opposed to tenofovir disoproxil fumarate)
– the antiviral therapy should be initiated at the time of transplantation, the duration of use varies i.e., some experts give it indefinitely while others discontinue it once the immunosuppression has been reduced then they monitor the patient closely
– for recipients with chronic HBV infection (HBsAg positive and HBcAb positive): – to prevent reactivation, all recipients with chronic HBV infection should receive antiviral therapy (entecavir and tenofovir alafenamide) indefinitely, the agent chosen depends on the patients’ prior antiviral history
– the goal of treatment in chronic HBV patients is virologic suppression
– monitoring and management of reactivation: –
among HBsAg positive patients, reactivation of HBV replication is defined by the appearance of HBV DNA in a patient who previously had undetectable HBV DNA or by a >1 to 2 log (10- to 100- fold) increase in HBV DNA
among HBsAg negative patients, HBV reactivation is defined by appearance of HBV DNA or the reappearance of HBsAg
recipients on antiviral therapy to prevent disease reactivation or flare should get serum aminotransferases and HBV DNA done every 6 months or as indicated
for recipients with prior HBV infection who had the antiviral therapy discontinued after immunosuppression was decreased should have serum liver chemistries, HBV DNA and HBsAg done every 3 months for 1year
if reactivation occurs then the patients should be reinitiated on the antiviral therapy
patients with a positive HBsAg need surveillance for HCC
References
1. Veroux M, Ardita V, Corona D, Giaquinta A, Ekser B, Sinagra N, et al. Kidney Transplantation From Donors with Hepatitis B. Medical science monitor : international medical journal of experimental and clinical research. 2016 Apr 28;22:1427-34. PubMed PMID: 27123988. Pubmed Central PMCID: PMC4915324. Epub 2016/04/29. eng.
2. 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.
3. 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.
Temporary state of cleared HBV infection before anti HBs in acute infection occur.
Decreased immunity from immunosuppression with loss of anti HBs.
Chronic infection with mutated HBsAG
Occult infection.
Previous blood transfusion
I will accept the donor as he is low risk but then rule out false positive in donor by a pepeat assay and equally do HBV DNA in donor to rule out an occult infection. As for the recipient we will need a full screen to establish status and rule out an occult infection; HBsAG, HBsAB, HBeAG and HBV DNA,. We would then monitor LFTS,HBV DNA and HBsAG at 1 month, then every 3 months and treat HBV if reactivation occurs post transplant.
HBcAB positivity with anti-Hbs positivity means previous infection and immunity, but here we may have an occult infection, and we need the HBV-DNA. as this is an emergent situation, not to waste the donor’s kidneys, I accept the patients with the support of anti-HBV treatment and HBV Immunoglobuline just as I accept HBsAg positive and consult a gastroenterologist or infectious diseases after detection of HBV DNA and I will repeat the HBV DNA and serology later
Will you accept this DBD donor? In this case HBcAb is positive and HBsAg negative, HBsAb negative are negative. Positive HbcAb can be due to previous immunity , seroconversion / Acute phase window, occult infection or false positivity. HBeAg and HBeAb are negative , so HEV infection is ruled out. Next step would be to check HBV DNA levels. Yes I will accept this DBD donor.
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met? Both donor and recipient are HbcAb positive . This will require further testing. HBV DNA titres should be checked. HBsAb Titres > 10 IU/L are protective if donor is HbcAb positive. If recipients has both HBsAg and HBsAb positivity , the he is a carrier. So in conclusion if both donor and recipient are HbcAb positive then both should be screened.
👉I will accept the deceased donor, as Postive anti HB C IgG means old infection with very low risk of transmission, however, prophylactic lamivudine for 6 months can be used.
👉 If he is live donor,
_ serological testing for the recipient by HBsAg, anti HBs IgM and IgG, HBc IgM and IgG, if any antibody postive …do HBV PCR.
_exclusion of occult infection in the live donor by HBV PCR is essential before accepting him as donor as there is risk of transmission.
Will you accept this DBD donor?
Yes, if recipient is immune either by natural infection or by vaccination and has protective anti HBs antibody
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
No, not straightaway.
if recipient is HBsAg negative, HBV DNA negative and is then vaccinated. Once protective anti HBs antibody develop after vaccination then transplantation can be considered
HBsAg negative, HBsAb negative, HBcAb positive, HBeAg negand HBeAb negative. Both HCV and HIV are negative.
Yes I will accept this DBD
It is a case of accult infection if the HBV DNA is negative
The
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
Yes we will accept this donor but also we should perform HBV DNA
In the condition of , we should study the recipient serological tests
HBeAG,
HBeAB,
HBsAG,
HBsAB,
and HBV DNA
HBcAB positivity with anti-Hbs positivity means previous infection and immunity, but here we may have an occult infection, and we need the HBV-DNA. as this is an emergent situation, not to waste the donor’s kidneys, I accept the patients with the support of anti-HBV treatment and HBV Immunoglobuline just as I accept HBsAg positive and consult a gastroenterologist or infectious diseases after detection of HBV DNA and I will repeat the HBV DNA and serology later
DD with anti-HBC positive (prior infection) the risk of transmission is negligible unless the donor is HBV DNA positive, in which case prophylactic antiviral therapy is recommended for one year, including entecavir and tenofovir
– kidneys from a HBcAb positive organ donor can be used on any recipient since the risk of de novo HBV infection is low so is the risk of HBV transmission
– unless there is a positive HBcAb IgM or positive HBV DNA
– however, the recipient should receive antiviral prophylaxis with either entecavir or tenofovir
– HBIG can be considered if there is no response to antiviral therapy
References
1. Veroux M, Ardita V, Corona D, Giaquinta A, Ekser B, Sinagra N, et al. Kidney Transplantation From Donors with Hepatitis B. Medical science monitor : international medical journal of experimental and clinical research. 2016 Apr 28;22:1427-34. PubMed PMID: 27123988. Pubmed Central PMCID: PMC4915324. Epub 2016/04/29. eng.
2. 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.
3. 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
this case scenario require more information about any blood transfusion, previous infections, exposure to HBV cases, drug abuser ,……etc
this case less likely to be occult infections as HBeV Ag & Ab negative
this case need HBV DNA before final decision yes i accept this case because categorized as low risk if previously infected , with close monitoring +/- lamivudine prophylaxis
I would accept this donor as the risk of de novo infection is low. HBcAb positive with negative HBsAg would suggest a previous infection, passively acquired antibodies from blood transfusion, acute hepatitis B infection or a false positive. It is important to get a history of any previous blood transfusion. The recipient may be offered lamivudine prophylaxis for 6 months after transplantation, although the risk of transmission is low
A HBcAb in the recipient will need to be investigated before transplantation. A careful history should be sought for any blood transfusion, risk factors for hepatitis B, testing for the full serological hepatitis B profile and the hepatitis B viral DNA. The risk of reactivation post transplant is estimated to be 1-5%. The recipients can either receive prophylaxis with lamivudine post transplant or can be floored up closely and monitored for reactivation
Guidelines for Hepatitis B and Solid Organ Transplantation, First Edition. British Transplantation Society
Thank you Professor Sharma
The presence of HBcAb alone does not confer protection. It is the presence of HBsAb more than 10 iU/ml that confer protection
The importance of HBcAb is the possibility of an occult infection
Will you accept this donor?
DBD with HBcAb positive and negative HBsAg and HBsAb.
Positive core antibody alone could occur from acute infection in the window phase, past infection or occult infection.
Hence in this donor it is important to get additional history on blood transfusion and any history of past Hepatitis B infection.
Additional test on NAAT for Hepatitis B and hepatitis D.
Yes I will accept this donor because the risk of de-novo infection in non-liver SOT is low.
Will you accept this donor if LDD and recipient also HBcAb positive? If yes, what conditions should be met?
Both donor and recipient are HBcAb positive, additional information of the recipient would be required.
Recipient HBsAg, HBsAb and HBV and HDV DNA.
HBsAb titers >10IU/L are considered to be protective for recipients receiving from HBcAb positive donors.
The recipients HBV DNA should be low or undetectable.
Recipient with high viral load will require entecavir/ tenofovir alafenamide prior to transplantation.
Yes I will accept this donor.
Recipient with high risk of reactivation will require lamivudine prophylaxis for 6 months post transplantation.
References
Guidelines for Hepatitis B & Solid Organ Transplantation First Edition March 2018
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
Thankyou,agree that in the second part of the scenario the recipient has to undergo tests to exclude OCULLT HBV
Mainly HBV DNA.
If the recipient has as well HBsAb so this incurs immunity.
If the the R has both HBs Ag+ and HBs Ab+ then he is a carrier.
Conclusion if this is LD with only HBc Ab + for both D and R the virology screen should be done for both.
In this indexed case of a DBD donor with
HBsAg negative
HBcAb positive
HBsAb negative
negative serology of HCV, and HIV screen, which indicates previous exposure with no immunity or controlled infection; resolving acute infection (window
period); or the possibility of occult HBV infection and there is a concern of reactivation after immunosuppression we need more history about the medical and social background of the donor including previous exposure, IV drug abuse, risky behavior, endemic area, infection screen in DD limited by the window period of infection
Anti-HBc of the IgM class indicates a current or recent infection with HBV, whereas anti-HBc of the IgG class indicates a past infection. The presence of hepatitis B surface antibody (HBsAb) in the blood is indicative of an immunologic response to HBsAg, and the higher the HBsAb titer, the lower the infectious risk associated with anti–HBc-positive donors which are not available in this case. Will you accept this DBD donor?
YES organs from these donors may be transplanted in certain cases with appropriate HBV prophylaxis similar to the indexed case
So the answer will be Yes after screening for silent HBV infection in the donor by NAT for HBV DNA. Check the recipient’s vaccination status and the HBs AB titer . one prospective study found that kidney transplantation using organs from anti-HBc IgG-positive donors (even when they are concurrently anti-HBs negative) in anti-HBs-positive recipients is a safe procedure and may be considered as a way to expand the donor pool (1).
Occult or silent HBV infection OBI refers to the status of negative hepatitis B surface antigen and positive/negative anti-hepatitis B core immunoglobulin G status but hepatitis B virus (HBV) DNA is detectable in serum and liver tissue. Genotypes A, C, G, E, and D have been found among patients with OBI in different regions of the world. Two types identified of silent HBV infection
1. Seropositive OBI, when the serum HBV DNA is detectable and both anti-HBc/anti-hepatitis B surface (HBs) IgGs are positive or only anti-HBc IgG is positive
2. Seronegative OBI. Only HBV DNA is detectable in serum/or liver tissue, but anti-HBc IgG/anti-HBs IgGs are negative in serum, it has been reported in up to 20% of cases of OBI. Patients at risk of OBI includes blood donors, health workers, hemodialysis patient, donors and recipients of SOT on immunosuppression, lymphoma, or other hematological malignancy on chemotherapy, co-infection with HIV, HCV with the impaired immune response they are at risk of reactivation of OBI with a previous history of HBV infection along with immunosuppression or chemotherapy status so to prevent such a risk the screening of HBV DNA should be implemented in blood donors, immunosuppressive patients, organ transplant donors, organ transplant recipients, and individuals with acute rheumatoid arthritis before and after treatment with anti-tumor necrosis factor (TNF)-α(2).
Will you accept this donor as a live donor if the recipient is also HB c Ab positive? If yes, what are the conditions that should be met?
This profile must be further investigated to clarify HBV status In patients with risk factors in the past for HBV infection: past, controlled infection; resolving acute infection (window period); or occult chronic infection. In patients with a recent history of blood/blood product transfusion: possible passively acquired anti-HB core antibody.
Donation is permitted if Anti-HBsAb titer >100 IU/L: with negative HBV-NAT, Between patients with past HBV (HBsAg negative, HBcAb positive), reactivation is more likely to occur in those with low or undetectable HBsAb levels and may be preceded by a fall in HBsAb levels over time.
it is recommended that HBV DNA is carried out in both donors and organ transplant recipients by highly sensitive molecular means. OBI reactivation may take place with increasing HBV DNA replication in patients during immunosuppression therapy. The risk of HBV reactivation is considered as high as 21% to 67%, especially with anti-CD20 rituximab and alemtuzumab with a mortality rate reported up to 20%. References
1. Abrão JM, Carvalho MF, Garcia PD, Contti MM, Andrade LG. Safety of kidney transplantation using anti-HBc-positive donors. Transplant Proc. 2014 Dec;46(10):3408-11.
2.Makvandi M. Update on occult hepatitis B virus infection. World J Gastroenterol. 2016 Oct 21;22(39):8720-8734. doi: 10.3748/wjg.v22.i39.8720. PMID: 27818588; PMCID: PMC5075547.
3.González R, Torres P, Castro E, Barbolla L, Candotti D, Koppelman M, Zaaijer HL, Lelie N, Allain JP, Echevarría JM. Efficacy of hepatitis B virus (HBV) DNA screening and characterization of acute and occult HBV infections among blood donors from Madrid, Spain. Transfusion. 2010;50:221–230.
4. Sowole L, Labbett W, Patel M, O’Riordan A, Cross J, Davenport A, Haque T. The prevalence of occult hepatitis B virus (HBV) infection in a large multi-ethnic hemodialysis cohort. BMC Nephrol. 2015;16:12.
5. White SL, Rawlinson W, Boan P, Sheppeard V, Wong G, Waller K, Opdam H, Kaldor J, Fink M, Verran D, Webster A, Wyburn K, Grayson L, Glanville A, Cross N, Irish A, Coates T, Griffin A, Snell G, Alexander SI, Campbell S, Chadban S, Macdonald P, Manley P, Mehakovic E, Ramachandran V, Mitchell A, Ison M. Infectious Disease Transmission in Solid Organ Transplantation: Donor Evaluation, Recipient Risk, and Outcomes of Transmission. Transplant Direct. 2018 Dec 20;5(1):e416.
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
yes I will accept
· HEV RNA SHOULD BE DONE TO EXCLUDE OCCULT INFECTION
· vaccination should be considered to boost the protective titre of HBsAb and minimise the risk of reactivation.
· Discussion with a specialist in viral hepatitis.
Please clarify your answer:
Who is immune.
Who is a healthy carrier
Who has a past infection and is also immune
Who has occult infection
TRY again.
then I will give you the answer!
The kidneys, heart & lungs from the HBcAb positive organ donor can be used for any recipient, & the risk of de novo HBV infection is low. (1A)
========================= Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
Yes, I will accept him.
It is suggested that:
lamivudine prophylaxis may be given for six months after transplantation, although the risk of transmission is very low. (2C)
The appropriate matching of an organ recipient with a donor positive for HBsAg or HBcAb should be discussed with a specialist in viral hepatitis. (2C)
All potential recipients should be counselled during the assessment process about the possibility of receiving a liver from a donor with past or current HBV infection.(Not graded)
Reference
British Transplantation Society Guidelines for Hepatitis B & Solid Organ Transplantation, March 2018
In LD in the given situation (D,R are HBc Ab +) to clarify the status of each
The index D will still need a HBV DNA to rule out OCCULT HBV.
As for the R he will need a full screen ,and also rule out occult HBV.
Will you accept this DBD donor?
o Yes, I will accept this deceased donor with only HBcAb positive as HBV seroconversion risk is low and no excess risk of graft failure or short-term morbidity
o Kidneys from HBcAb positive organ donor can be used for any recipient and the risk of de novo HBV infection is low (Guidelines for Hepatitis B & Solid Organ Transplantation. British Transplantation Society Guidelines, 2018
o One review of core antibody positive donation to a large number of renal transplant recipients found that 45/1385 (3.2%) developed new HBV serological markers, but HBsAg seroconversion was seen in only four (0.28%) patients
o With this isolated HBcAb positive donor, lamivudine prophylaxis may be given for six months after transplantation, although the risk of transmission is very low
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
o This case should be discussed with a specialist in viral hepatitis
o Ask for recent HBV exposure (HBC IgM )
o HBcAb positive but HBsAg negative potential recipient (past infection): do HBV DNA and HDV serology testing to exclude occult HBV or HDV infection
o In HBcAb positive patient (past resolved infection), if HBsAb are <100 IU/mL, give vaccination to boost the protective titre of HBsAb and minimise the risk of reactivation
o Reactivation in patients with past resolved HBV infection (i.e. HBsAg negative/HBcAb positive is around 6.5% (particularly amongst recipients without HBsAb at the time of renal transplantation)
o HBV DNA and HBsAg should be monitored every 3 months in the first year and thereafter every six months individuals receiving a graft from a HBcAb positive donor, regardless of treatment or prophylaxis regimen
Serological markers for HBV infection
HBsAg, anti-HBs, HBeAg, anti-HBe, and anti-HBc IgM and IgG
HBsAg:
o Appears in serum within 1 to 10 weeks after exposture
o Persistence more than 6 months implies chronic HBV infection
o Titers are higher in patients with HBeA gpositive chronic hepatitis B (CHB) than in HBeAg-negative CHB
Anti-HBs (neutralizing antibody):
o Confers long-term immunity
o Are unable to neutralize the circulating viruses in most cases (so regarded as carriers of HBV)
o It is the only serological marker for vaccination
o Simultaneous appearance of HBsAg and anti-HBs may occur in patients with HBsAg positive
HBeAg and anti-HBe:
o For Infectivity and viral replication (replaced by HBV DNA)
o Seroconversion is related to the remission of hepatic disease
o Active viral replication is sustained in some patients with HBe seroconversion due to mutations in the pre-core and core region that inhibit or decrease the production of HBeAg
HBc Ag:
o Intracellular in infected hepatocyte and is not identified in the serum
anti-HBc:
o During acute infection, anti-HBc IgM and IgG appears 1–2 weeks after the presence of HBsAg along with raised serum aminotransferase and symptoms
o Anti-HBc IgM wears off after 6 months of acute infection
o Anti-HBc IgG continues to detect in both patients with resolved HBV infection and CHB
o Some HBsAg-negative individuals are positive for anti-HBc IgG without anti-HBs (isolated anti-HBc positive)
o Isolated anti-HBc positive seen in 3 conditions:
1. seen as IgM class during the window period of acute phase
2. after acute infection ended, anti-HBs has decreased below the cutoff level of detection
3. after several years of chronic HBV infection, HBsAg has diminished to undetectable levels
o In isolated anti-HBc positive, anti-HBc IgM should be checked to assess the possibility of recent HBV exposure
o HBV DNA should be tested in chronic liver disease patients to find out occult HBV infection (existence of detectable HBV DNA without serum HBsAg)
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.
Kidney of 59- year male, DBD, HBsAg , HBsAb were negative. HBcAb positive, HBeAg and HBeAb were negative, Both HCV and HIV were negative.
1. Will you accept this DBD donor?
This donor has past HBV infection
Yes will accept this DBD donor
· Check the donor PCR if feasible.
· The risk for HBV transmission to the recipient in renal transplantation, seems to be low, especially in successfully vaccinated (anti-HBs concentration of <10IU/Ml)
· If the recipient is HBsA g positive.
· Lamivudine prophylaxis may be given for six months after transplantation or an HB Ig single-shot prophylaxis may reduce the risk of HBV seroconversion or reactivation.
· HBcAb-positive transplant recipients should be followed for the development of HBV by checking serologies for seroconversion.
2. Will you accept this donor as a living donor if the recipient is also HBc Ab positive? If yes why?
Yes will accept
· Will check for immunity status of recipient, if anti-HBs concentration of <10IU/mL will give HBV vaccine.
· Prophylaxis for recipients of HBcAb-positive kidneys using lamivudine may give protection.
· If the level of anti-HBs concentration of >10 IU/mL no need for prophylaxis as this level is considered protective.
· Important is close follow up with serum ALT, HBV DNA, and seroconversion, for evidence do novo infection.
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
This potential donor is positive for HBc-Ab, although, not determined which one of anti-HBc antibody is positive. The followings may further explain this case scenario(1):
· The potential donor may have an occult HBV infection:Occult HBV infection is defined by persistence of low level of intrahepatic HBV DNA without detectable HBsAg. It is a serological situation defined by the presence of isolated anti-HBc with the absence of HBsAg and anti- HBs antibody.
· The potential donor may be in the window period of acute phase: seen predominantly as IgM class.
· The potential donor may have an acute HBV infection that had ended: anti-HBs has decreased below the cutoff level of detection. Patient in the convalescence phase with the detectable HBc-Ab mostly to be of IgM type.
Overall, I will accept this potential donor and proceed forward in the transplant process.
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(2). I will consider antiviral therapy for the recipient.
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
The HBcAb positive organ donor can be used for any recipient, and the risk of de novo HBV infection is low. 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(2).
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): As long as HBcAb positive donor is used, lamivudine prophylaxis may be given for six months after transplantation, although the risk of transmission is very low.
References
1. 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.
2. Guidelines for Hepatitis E & Solid Organ Transplantation; first edition (BTS guidelines)
I would accept this DBD donor but need to manage the recipient for denovo HBV infection according to his/her HBV status.
we can stratify the recipient as
•High risk recipient- HbsAg-ve, Anti Hbc-ve, anti hbs-ve(susceptible)
•Moderate risk- HbsAg+ve, anti Hbc igg+ve, Anti hbs –ve (chronically infected) and
Hbsag-ve, Anti hbc+ve, Anti hbsAg-ve (prior infection)
Mild risk recipient- HbsAg-ve, Anti Hbc+ve, Anti Hbs+ve(immune due to natural infection) and Hbsag-ve, Anti-Hbc-ve, Anti Hbs+ve (immune due to vaccination) Antiviral for prevention of denovo infection and re activation Life long- antiviral for moderate risk One year for high risk, mild risk Antiviral to be started at the time of transplantation
and need to monitoring HBsAg, HBcAb every 3 month for 1 year, then every 6 months DNA (NAT)
Choice of antiviral
Entecavir or tenofovir alafenamide (if patient had received lamivudine in past, then preferred tenofovir alafenamide)
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
Yes will accept this donor as live donor only if HBcAb Igm of recipient is negative
If the recipieent is HbcAb positive he may be
Moderate risk recipient- HbsAg+ve, anti Hbc igg+ve, Anti hbs –ve (chronically infected) and
Hbsag-ve, Anti hbc+ve, Anti hbsAg-ve (prior infection)
or
Mild risk recipient- HbsAg-ve, Anti Hbc+ve, Anti Hbs+ve(immune due to natural infection)
Need to see HBV DNA load and liver enzymes (withing normal limits)
Antiviral for prevention of denovo infection and re activation Life long- antiviral for moderate risk One year for high risk, mild risk
and need to monitor HBsAg, HBcAb every 3 month for 1 year, then every 6 months DNA (NAT)
Choice of antiviral
Entecavir or tenofovir alafenamide (if patient had received lamivudine in past then preferred tenofovir alafenamide)
Induction agents– consider basiliximab instead for lymphocyte depleted and steroid free manintanence immunosuppression. not to use rituximab
1)Lecture : May A Hassaballa HEV in kidney transplant
2)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.
We accepted this patient who HBcAb positive with negative HBsAg .
The HBcAb positive (HBsAg negative) donor liver can be used for any potential liver recipient.
When the liver comes from a HBcAb positive donor and is given to a HBV immune or non-immune recipient, prophylactic lamivudine for 6 month should be given from the time of transplantation.
Donation of non-liver solid organs from the core antibody positive donor is rarely associated with de novo infection of the recipient.
Though serological signs of HBV infection may be documented (such as the development of HBcAb in a non-immune recipient), serum HBsAg seroconversion (de novo infection) is rarely observed with this postive HBcAb and negative to HBsAb,HBsAg ,HBeAb and HBAg may reflect prior infection and liable to reactivation there for HBVDNA testing is mandatory.
Monitor HBV DNA, and HDV serology, every 3 months in the 1st year and then every 6 months thereafter and accordingly.
According to the antibody titer recipient should receive HB vaccination.
One review of core antibody positive donation to a large number of renal transplant recipients found that 45/1385 (3.2%) developed new HBV serological markers, but HBsAg seroconversion was seen in only four (0.28%) patients [12].
With such a low risk for de novo infection, it is hard to demonstrate a benefit of antiviral prophylaxis.
Pre-transplant recipient HBV immunity appears to protect against de novo infection. Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
Yeas I will .
HBcAb may differentite as :
HBsAg+ve recipient.( Lamivudine administered for one year if donor HBV PCR is positive along with HBV immunoglobuline)
Hepatitis B immune recipient.( with anti-Hepatitis B s antibody titer of more than 10 IU/ml)
Hepatitis B non-immune recipient.( single dose of 2000 HBV immunoglobulin if HBV PCR was not done)
Reference
1.Mahboobi N, Tabatabaei SV, Blum HE, et al. Renal grafts from anti hepatitis B core positive donors. A quantitative review of the literature. Transpl Infect Dis 2013; 14: 445-51.
2.Pilmore HL, Gane EJ. Hepatitis B positive donors in renal transplantation: increasing the deceased donor pool. Transplantation 2012; 94: 205-10.
3.Rosemary Ouseph et al. Review of the use of hepatitis B core antibody–positive kidney donors.Transplantation ReviewsVolume 24, Issue
The DD ‘s liver can harbour in this case a state of occult HBV so a HBV DNA is a must if you decide to use this liver, or at least a prophylaxis should be strongly implemented .
Stored samples from a DD are very informative when needed.
Hepatitis B virus (HBV) infection is a major risk factor for liver injury after kidney transplantation. As an Anti-HBc IgM and IgGrise in 1–2 weeks after the presence of HBsAg along with raised serum aminotransferase and symptoms during acute infection (window period). After 6 months of acute infection. anti-HBc IgM becomes negative, and Anti-HBc IgG positive in resolved HBV infection and Chronic HB. Thus, donor medical chart, and detailed history might be informative to clarify the distinct of HBV status( either acquired by blood product transfusion, resolving acute infection, or occult chronic infection), so HBV PCR should also be taken from the donor- UK guidelines stated that: All donors who are positive for HBcAb but HBsAg negative (past HBV exposure) must have HBV DNA testing to exclude the possibility of occult HBV infection. (1C) Amongst patients with past HBV (HBsAg negative, HBcAb positive), reactivation is more likely to occur in those with low or undetectable HBsAb levels and may be preceded by a fall in HBsAb levels over time. I would check the recipient vaccination chart for hepatitis B if HBs Ab titer > 10 means that he is immunized, so I would do transplant such a patient. But I would explain the risk of having active disease, with fulminant hepatitis, and death. Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
Yes, I will accept this living donor with anti HBc Ab But before I would ask for HBs Ab, HBs Ag, and HBe Ab. Anti-HBc antibody positive (HBsAg negative) patients should not be excluded from kidney transplantation (1C). Anti-HBc antibody positive (HBsAg negative) patients should not receive antiviral prophylaxis given that the risk of reactivation is low (1D). Anti-HBc antibody positive (HBsAg negative) patients have a plan in place for post-transplant monitoring of HBsAg and HBV DNA for a minimum of 1-year post-transplantation.(1C)
If the donor has a chronic infection of Hepatis B – in spite of low risk of viral infection the recipient should receive anti- viral prophylaxis for up to one year with lamuvidin most widely used. Ensure that the recipient is immunized – received HB vaccine with anti HBs AB >10 , this strategy found to be protective. References: (1) Abrão JM, Carvalho MF, Garcia PD, Contti MM, Andrade LG. Safety of kidney transplantation using anti-HBc-positive donors. Transplant Proc. 2014 Dec;46(10):3408-11. doi: 10.1016/j.transproceed.2014.06.067. PMID: 25498061. (2) Chadban, Steven J. BMed, PhD1,*; Ahn, Curie MD, PhD2; Axelrod, David A. MD, MBA3; Foster, Bethany J. MD, MSCE4; Kasiske, Bertram L. MD5; Kher, Vijah MD, DM6; Kumar, Deepali MD, MSc7; Oberbauer, Rainer MD, PhD8; Pascual, Julio MD, PhD9; Pilmore, Helen L. MD10; Rodrigue, James R. PhD11; Segev, Dorry L. MD, PhD12; Sheerin, Neil S. BSc, PhD13; Tinckam, Kathryn J. MD, MMSc7; Wong, Germaine MD, PhD14; Knoll, Gregory A. MD, MSc15,*. KDIGO Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation. Transplantation 104(4S1):p S11-S103, April 2020. (3) 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.
The index patient is being offered a DBD (donor after brain death) donor with good terminal renal function. The donor is HBcAb positive. Other serological tests (HBsAag, HBeAg, HBeAb, HIV and HCV) are negative.
Positive Anti-HBcAb signifies either a resolving acute infection (Anti HBcAb IgM positive), or a resolved HBV infection (Anti HBcAb IgG positive), or a low level chronic infection (HBV DNA PCR positive).
As per the British Transplantation Society guidelines, kidneys from HBcAb positive donors can be used for any recipient, the risk of de novo HBV infection being low (1).
Hence, I will accept this DBD donor.
Lamivudine prophylaxis for 6 months post-transplant can be given to the recipient if the recipient is non-HBV immune (1,2).
If the recipient is anti-HBs positive (HBV immune), then there is no need of antiviral prophylaxis (3).
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
Yes. A HBcAb positive live donor can be accepted for HBcAb positive recipient (1).
Donor: In case a live donor, if during pre-donation evaluation, is found to be HBcAb positive and HBsAg negative, then HBV DNA testing of the donor should be done (to rule out occult HBV infection). The prospective donor should be evaluated thoroughly including liver function tests and abdominal ultrasound. The type of HBcAb (IgG or IgM) should be tested.
Recipient: If the recipient is also HBcAb positive, other markers like HBsAg, HBsAb, HBeAg, HBeAb, and HBV DNA PCR and HDV serology (to rule our HDV co-infection) should be done.
If HBcAb positive and Anti-HBsAb <100 IU.ml, vaccination should be considered for the recipient to boost HBsAb titres.
It has been recommended that routine antiviral prophylaxis (tenofovir or entecavir) are not required in those with markers of past HBV infection (HBsAg negative, HBcAb positive, with or without Anti-HBsAb), but they may be given if the recipient is Anti-HBcAb positive alone, or has detectable HBV DNA, or requiring intense immunosuppression like rituximab, ATG use (3).
So, in this scenario, if only HBcAb is positive in recipient, antiviral prophylaxis would be required.
Patient should be monitored with liver enzyme, HBsAg and HBV DNA once in 3 months for at least 1 year post-transplant, and during periods of intense immunosuppression, if prophylaxis is not given and antivirals can be initiated if HBsAg becomes positive or HBV DNA titres rise (1,3).
In nutshell, this clinical scenario requires:
1) Recipient should be counselled regarding the clinical scenario.
2) Hepatologist should be involved in management.
3) Donor HBV DNA should be checked.
4) Recipient should be vaccinated.
5) Post-transplant antiviral prophylaxis would be required.
6) Regular post-transplant monitoring of LFT, HBsAg and HBV DNA should be done as per protocol.
Ouseph R, Eng M, Ravindra K, Brock GN, Buell JF, Marvin MR. Review of the use of hepatitis B core antibody-positive kidney donors. Transplant Rev (Orlando). 2010 Oct;24(4):167-71. doi: 10.1016/j.trre.2010.05.001. Epub 2010 Jul 23. PMID: 20655722.
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.
Thankyou well done ,the -ve HBeAg, and HBeAb means he has no virus replication(no or low INFECTIVITY) so your vaccination/prophylaxis plan is correct.
In the second part of the scenario you well confirmed a full virology screen for the R with HBV DNA and a well planed vaccination/prophylaxis.
well done very well structured (not just copy ,paste guidelines.
Will you accept this DBD donor?
Yes, with the current marked imbalance between the supply and demand for organs, this donor can be accepted.
BTS clearly stated that non-liver solid organs from the HBcAb positive organ donor can be used for any recipient, and the risk of de novo HBV infection is low.
Isolated HBcAb can be seen in the following condition:
– Window period of acute phase; predominantly IgM class.
-After acute infection had ended, anti-HBs has decreased below the cutoff level of detection.
-After several years of chronic HBV infection, HBsAg has diminished to undetectable levels.
In this case we should check the possibility of:
– Recent HBV exposure by anti-HBc IgM.
– Occult HBV infection(existence of detectable HBV DNA without serum HBsAg) by checking Real time PCR (HBV DNA assays)
– Despite the low risk of transmission is very low, lamivudine prophylaxis may be given for 6 months after transplantation, when a HBcAb positive donor is used. Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
Yes, this donor can be accepted and we need to rule out the possibility of :
– Recent HBV exposure.
– Occult HBV infection.
Occult HBV infection is defined by:
– Persistence of low level of HBV DNA without detectable HBsAg
– Presence of isolated anti-HBc with the absence of HBsAg and anti- HBs antibody
-The detection of HBV DNA in the liver is the gold standard of diagnosis for occult HBV, invasive and not performed usually.
The clinical importance of Occult HBV infection: .
– Transmission via transfusion, SOT or hemodialysis
– Risk of reactivation of HBV in immunocompromised state.
– It may accelerate liver injury and lead to hepatic fibrosis
– it is a risk factor for HCC.
In this setting check the donor for:
– LFT enzymes.
– HBV DNA ( PCR)
– Repeat serology; HBcAg IM and IgG
– Check for co-infection with HDV.
– Liver US
For the recipient:
– Check HBV status; serology HBsAg, HBsAb, HBcAb IgG& IgM, HBV PCR, HDV. Other viruses as per guidelines.
– Lamivudine prophylaxis may be given for 6 months Post-KT t, although the risk of transmission is very low although monitoring for HBV recurrence is an equally acceptable strategy.
– Monitoring for HBV Recurrence or De Novo Infection; HBV DNA and HBsAg should be monitored every 3 months in the first year and then every 6 months in HBsAg positive liver transplant recipients or
individuals receiving a graft from a HBcAb positive donor, regardless of treatment or prophylaxis regimen.
– Recipient will ideally have been effectively immunized against HBV.
– KTR with HBcAb positive, if HBsAb are <100 IU/mL, should be vaccinated to decrease transmission risk
– High-dose, accelerated vaccine schedule, second series can be given if no response.
– KTR who have a resolved infection of HBV (defined by positive anti-HBc serology) should be aware of a possibility of HBV reactivation during a course of intensive IS particularly Rituximab ( regardless donor status)
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.
I would accept this donor because he is HbsAg negative, anti HBc positive, both HBeAg and HBeAb negative. This donor is non-infectious to others.
However, there is risk of de novo HBV in recipient with this donor.
Since donor is HBcAb positive, recipient can be given lamivudine prophylaxis for 6 months post transplant.
If recipient has history of HBV infection previously with reports of HBcAb positivity, then the recipient could be at risk of this infection reactivating post transplant. Thus, I would consider 6 months prophylaxis of antiviral therapy. Careful monitoring for HBV recurrence is also necessary in this recipient.
If recipient is HBV naive, then vaccination has to be done.
Live donor with HBcAb positive recipient
Since recipient is HBcAb positive, if titles are below 100 IU/ml then he/she should be vaccinated in order to reduce incidence of reactivation. If the patient fails to respond, then second series can be considered.
Since donor is live, test for HIV, HEV and HCV active infection.
Do HBV DNA for the donor to check for occult infection.
If donor has no active viral infection, has HBV DNA undetected, then I would accept this live donor.
Do HBV serology every 3 months in the first year post transplant, followed by twice a year from second year onwards.
References :
1.Prof May Hassaballa. Kidney Tx in patients with HBV, HEV. Cairo University. World kidney Academy. 2023.
2.BTS. Guidelines for Hepatitis B & Solid organ transplantation. 2023.
Agree if the living donor is -ve for HBe Ag ,HBe Ab therefore he has no virus REPLICATION.
However you still need HBV DNA ,if that is -ve then the R can be vaccinated and LAMIVUDINE prophylaxis.
Interpretation of results for isolated anti-HBc. There are different possibilities which includes the following:
A window period of acute hepatitis B when the anti-HBc is majorly IgM.
An undetectable level of anti-HBs following recovery from acute hepatitis B.
An undetectable level of HBsAg in a state of chronic hepatitis B.
A false negative result due to mutation of HBsAg.
A false positive anti-HBc result.
In order to determine the source and significance of the anti-HBc positivity, a repeat testing for anti-HBc, HBsAg, anti-HBs and anti-HBe is checked.
A repeat positive antibody to core antigen with history of recent exposure to HBV and symptoms of hepatitis and/ or evidence of transaminitis will require anti-HBc IgM to rule out recent infection.
An acute infection is a contraindication to transplantation for both donor and recipient. However, in extreme cases such as in those on dialysis with access line exhaustion or those who are not tolerating dialysis, transplantation may proceed with antiviral prophylaxis.
HBV DNA level should also be checked in isolated anti-HBc antibody.
This is to rule out occult infection which has an elevated risk of chronic liver disease and hepatocellular carcinoma.
If DNA is detected, such patients should be treated with antiviral agents to suppress DNA to undetectable levels before transplantation except in extreme cases as highlighted above. Additionally, patient should be screened for other viruses such as HCV, HIV etc. Evaluation for liver cirrhosis and malignancy such as liver scan, serum alpha-fetoprotein etc. may also be done.
If DNA is undetected, a recipient with isolated antibody to core antigen can be offered a booster dose of HBV vaccine. If serum antibody to HBsAg is at least 10mIU/ml after 1 month, it is likely a previous infection. However, if there is no response it is likely a chronic HBV infection with loss of HBsAg or occult HBV. Otherwise, it could be a case of vaccine non responder like in CKD patients with impaired immune response.
Will you accept this DBD donor? Yes. However, if the recipient has no previous infection or vaccinated, transplantation the donor will not be accepted except in extreme cases. The recipient will also need to be on prophylaxis with either entecavir or tenofovir.
Rationale is that this could be a potential case of either an acute or even a chronic infection as highlighted earlier and may constitute a high risk for the recipient especially if recipient is immune naive.
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
Yes, and the conditions will include:
Rule out an active infection using the HBV DNA.
If an active infection is present with high HBV DNA, donor will be on treatment to suppress HBV DNA to undetectable level before donation except in extreme cases.
A donor with active infection should also be screened for other viruses such as HIV, HCV, HEV.
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
I like your analysis. However, you mention as I quote you, “donor will be on treatment to suppress HBV DNA to undetectable level before donation except in extreme cases.” My question to you: Do you really have enough time to treat DBD donor with anti-viral ?
Both adopted & innate immunity response are vital in controlling HBV infection, so post transplantation use of immunosuppression can alter the natural history of HBV infection causing progressive hepatic injury & damage with increasing morbidity & mortality.
Risk of HBV reactivation depend on both donor & recipient immune status.
This donor had anti-HBc Ab & negative HBsAg mean past infection.
According BTS guidelines potential donor with positive HBcAn & negative HBsAg can be used to any recipient with low risk of de novo HBV infection.So yes I will accept this donor & 6 months of lamuvidin as prophylaxis can be used post transplantation.
If the donor is a live :
Accepting a live donor with HBcAb+ve/HBsAg-ve depend on HBV immune status of the recipient to determine the risk of transmission or reactivation of HBV infection.
Recipient : HBsAg-ve /HBsAb+ve =low risk
HBcAb-ve/ HBsAb-ve =low risk
HBsAg-ve/ HBsAb-ve =low to moderate risk.
HBcAb+ve/ HbsAb-ve =moderate to high risk.
HBsAg+ve/ HbcAb+ve = very high risk
In addition donor HBV RNA quantification is important to exclude occult infection.
I will accept live donor after excluding of occult infection & low risk recipient
Reference:
BTS guidelines for Hepatitis B & Solid Organ Transplantation, 18th edition,2018.
· Will you accept this DBD donor?
Yes as the donor has no active infection but immune by natural old infection the risk of getting HBV infection is low But the following is required
Evaluation of HBV DNA and HDV RNS for any dormant infection
Lamivudine prophylaxis is recommended life long
Testing every 3 months for HBV and HDV serology for the 1st year then every 6 months after 1styear Will you accept this donor as a liver donor if the recipient is also HBcAb +ve? Yes of course with the same protocol mentioned above Ref https://bts.org.uk/wp-content/uploads/2018/03/BTS_HepB_Guidelines_FINAL_09.03.18.pdf
-Will you accept this DBD donor?
Yes can be accepted according to the recipient virological status and immunity certain considerations .
HBcAb positive donors can be donated to any recipient, as de novo HBV infection is low meanwhile lamivudine prophylaxis may be given for 6 months after transplantation.
This donor is HBc Ab positive while HBsAb ,HbsAg ,HBe Ag and HBe Ab are negative means that he had prior HBV infection and is liable to reactivation
HBV DNA testing is needed
So the risk of HBV infection transmission to the recipient from this Hbc Ab positive donor will vary according to virological recipient’s status so
· If the recipient had HBs Ag,HBs Ab, HBc Ab negative ,he will be highly susceptible to develop HBV infection
· If the recipient had HBs Ag, negative and HBs Ab, HBc Ab are positive then he will be immune due to natural infection and the risk will be low
· If the recipient had HBs Ag, HBc Ab negative HBs Ab is positive denoting vaccination and immunity also the risk will be low
· If the recipient had HBs Ag, HBc Ab, HBc Ab Ig M positive , HBs Ab is negative indicating acute infection so it suitable to receive this donor’s graft
· If the recipient had HBs Ag, HBc Ab, positive and HBs Ab, HBc Ab Ig M are negative indicating chronic infection so the risk will be moderate
· If the recipient had HBc Abpositive and HBs Ag, HBs Ab are negative the same as the donor virological status indicating also previous HBV infection ,therefore the risk will be moderate
In this case the recipient has to receive antiviral therapy at the time of transplantation and to monitor carefully the immunosuppression and titrate the dose as needed to maintain immunity against the HBV infection and at the same time guard against rejection risk .
Tenofovir with lower renal toxicity or entecavir according to creat. clearance dose adjustment can be given , it is preferred than Lamivudine for the sake of safety profile with long duration therapies
HBV DNA and HBsAg need monitoring every 3 months in the first year and then every 6 months
In fact Risk benefit has to be weighed with counselling of the recipient considering the age of the recipient, his medical condition and co morbidities ,matching and desensitisation need, time spent on waiting list
-Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
Yes ,Antiviral therapy can be given for lifelong in this case with prior HBV infection with monitoring /3 months for 1 years testing HB sAg HBcAb then every 6 months by testing HBV DNA
Reference
– Guidelines forHepatitis B & Solid Organ Transplantation, BTS March 2018
– Chan T M etal .Kidney transplantation in adults: Hepatitis B virus infection in kidney transplant recipients.Uptodate2022
You were offered kidneys from a 59-year-old male DBD (donor after brain stem death) donor who suffered from SAH (grade 5) complicating cerebral aneurysm. His retrieval S Cr was 72 µmol/L. Virology was reported as follows: HBsAg negative, HBsAb negative, HBcAb positive, and 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 HBcAb positive?
If yes, what are the conditions that should be met?
New infection or recovering from acute HBV infection.
Chronic infection with low antibodies. False-positive anti-HBc. Will you accept this DBD donor?
YES, IF; After HBV DNA status If donor is negative on HBV PCR testing. If Recipient is immunized with anti-Hepatitis B s antibody titer of more than 10 IU/ml and
preferably more than 100 IU/ml after boosting the recipient with anti HBV vaccine
If HBs Ab is more than 100 an HBV DNA in not detected, the infectious risk is low.
There are several reports of kidney transplanted from HBsAg/DNA negative.
the prospective recipient will effectively be immunized against HBV. single dose of 2000 HBV immunoglobulin if HBV PCR was not done.
The addition of antiviral drug may be considered especially in low HBs Ab response to
vaccination=> Lamivudine or Entecavir administered for one year if donor HBV PCR is positive along with HBV immunoglobulin.
Most transplant units will not accept potential donor with active viral replication. References; *British Transplantation Society Guidelines: March 2018.
*UpToDate
*Hyejin Mo et al. Outcome after kidney transplantation in hepatitis B surface antigen-positive patients. Scientific Reportsvolume 11, Article number: 11744 (2021)
Virology was reported as follows: HBsAg negative, HBsAb negative, HBcAb positive, and both HBeAg and HBeAb are negative. Both HCV and HIV are negative.
The possibilities of this results are :
1-New infection .
2-chronic infection with low antibodies .
Will you accept this DBD donor?
yes ,but I would like to do HBV DNA
if HBSAb is more than 100 an HBV DNA in not detected ,the infectious risk is low .
There are a number of reports of kidney transplanted from HBsAG/DNA negative
the prospective recipient will effectively immunized against HBV .
The addition of antiviral drug maybe considered especially in low HBs AB response to vaccination .
MOst transplant units will not accept potential donor with active viral replication .
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 evaluationwith isolated anti-HBc positivity (negative for both HBsAg and anti-HBs)
Isolated anti-HBc positivity may be seen in case of early infection (window period), occult infection, or resolved infection
Transplant recipients with isolated anti-HBc positivity, should be assessed using HBV PCR
If PCR is positive this means that the patient has occult infection
If PCR is negative this means either occult infection (virus in the liver) or previous infection, at that time a booster dose of vaccination can be given, if the titer increase ≥10 mIU/mL this means previous resolved infection but if the titer does not increase this means occult infection or previous infection with failure of vaccine due to impaired immunity related to CKD (1)
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
Donors with isolated anti-HBc positivity and negative PCR can be accepted routinely
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 anti-HBc positive donor to naive transplant recipient (Will you accept this DBD donor?)
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
Donors with HBsAg (-) anti-HBc (+) are routinely accepted whatever the immunization state of the recipient due to negligible risk associated with this seropositivity, except if the PCR is positive at that time the risk is high (2)
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 antiviral prophylactic therapy
Antiviral prophylaxis for at least 1 year is indicated in patients with antiHBs < 10 receiving kidney from anti-HBc (+) donors
Patients with antiHBs ≻10 receiving kidney from anti-HBc (+) donors should receive no prophylaxis except if PCR is positive
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
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 if given and testing should be done annually
Monitoring of antiHBs Ab yearly, and if < 10 a booster dose should be given,
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 previous infection (HBsAg negative, anti-HBc positive) (Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?)
Transplant recipients with prior infection can receive kidney from any donor regardless of HBV status
Transplant recipients with prior infection should receive antiviral therapy at the time of transplantation even if PCR is positive (< 5%) and antiHBs Ab is positive. No clear evidence of the optimal duration of antiviral (6), some recommends lifelong, others recommend 6 months to 1 year after transplantation in patients receiving high dose triple therapy, rituximab, belatacept or alemtuzumab and after rejection treatment
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)
Patient with positive anti-HBc are at high risk of reactivation with the use of even single dose of Rituximab (ABMR, ABO I transplantation), in this patient reinitiating prophylactic antiviral therapy is recommended.
In patients with prior infection regular check of serum ALT, HBV DNA and HBs Ag is indicated every 6 months while on antiviral, if treatment is stopped monitoring is indicated every 3 months for 1 year, then every 6 month thereafter except in intensification of immunosuppression is required at that time monitoring will be every 3 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
Patient who develop positive anti-HBc after resolution of infection are at high risk of reactivation with aggressive immunosuppression (especially Rituximab)
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 Ab for the recipient to evaluate the risk, I will accept this DBD donor with isolated anti-HBc positive to naive transplant recipients 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
The donor PCR and HBe antigen are negative
Antiviral prophylaxis should be received for at least 1 year is indicated only in patients with antiHBs < 10 or patients with antiHBs ≻10 with positive donor PCR
On the other hand, I will you accept this donor as a live donor if the recipient is also HBcAb positive since transplant recipients with prior infection can receive kidney from any donor regardless of HBV status under cover of life long or 1 year antiviral therapy with close monitoring
References
1- Chen GD, Gu JL, Qiu J, Chen LZ. Outcomes and risk factors for hepatitis B virus (HBV) reactivation after kidney transplantation in occult HBV carriers. Transpl Infect Dis 2013; 15:300.
2- Abrão JM, Carvalho MF, Garcia PD, et al. Safety of kidney transplantation using anti-HBc-positive donors. Transplant Proc 2014; 46:3408.
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- Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology 2018; 67:1560.
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 make note of your interpretation of serological and molecular testing reports pertaining to HBV infections in relation to timings in the natural history HBV infections. I like your summary.
Might have had prior infection and test not sensitive enough to detect very low level of anti-HBs in serum.
Might be susceptible with a false positive anti-HBc.
Might be undetectable level of HBsAg present in the serum, and the person is actually chronically infected.
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
YES ACCEPT
Recipients who are anti-HBc positive have evidence of prior infection, and HBV reactivation may occur secondary to immunosuppressive therapy. The presence of anti-HBs at time of transplantation may not prevent reactivation, because anti-HBs titer can decrease and become undetectable with immunosuppression.
The duration of antiviral therapy can vary. Some centers administer antiviral therapy indefinitely to all recipients with prior HBV. Others discontinue treatment when immunosuppression is reduced to low-dose maintenance level and monitor closely thereafter, unless the patient is receiving immunosuppression with an agent associated with a high risk of HBV reactivation (eg, rituximab).
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 chronic kidney disease and immunosuppressive medications.
If antiviral therapy is administered, the optimal duration is unknown; Aadminister therapy for 1 year.According HBV viral load
I will accept the donor,
Owing to the fact that HB c antibody positive donor might indicate a previous infection in the donor, even with HB s Ag negative status. risk of recipient seroconversion is 4 % if virology status showed Anti HB s Ab positive of a titer exceeding 10 iu/ml and risk of around 10% with lesser titer. nevertheless, risk of transmission is dependent on virology load, If PCR for HBV is positive then increasing risk of transmission necessitated the administration of HBV immunoglobulins and Lamivudine prophylactic therapy along with immunization of recipient. If he is non immunized. however, is PCR is negative then risk of transmission is negligible.
If the donor and recipient both are Hepatitis B core antibody positive , I will accept the donation if:
1] The donor is negative on HBV PCR testing.
2] Recipient is immunized with anti-Hepatitis B s antibody titer of more than 10 IU/ml and preferably more than 100 IU/ml after boosting the recipient with anti HBV vaccine.
3] single dose of 2000 HBV immunoglobulin if HBV PCR was not done .
4] Lamivudine administered for one year if donor HBV PCR is positive along with HBV immunoglobuline.
References:
1]Rosemary Ouseph et al. Review of the use of hepatitis B core antibody–positive kidney donors.Transplantation ReviewsVolume 24, Issue 4, October 2010, Pages 167-171.
2] Hyejin Mo et al. Outcome after kidney transplantation in hepatitis B surface antigen-positive patients. Scientific Reportsvolume 11, Article number: 11744 (2021)
The donor is only hepatitis B core Abs +ve
Interpretation unclear; four possibilities:
1. Resolved infection (most common)
2. False-positive anti-HBc, thus susceptible
3. “Low level” chronic infection
4. Resolving acute infection
Isolated positive hepatitis Bc Abs seems to be dismal for recipients of renal transplantation with potential risk of HBV during immunosuppression. Due to the risk of reactivation, prophylactic lamivudine or entecavir should be considered with regular testing of HBV DNA and HBsAg
In the era of kidney donors shortage, I will accept this donation.
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
considering the recipient has received a full vaccination for HBV, or if the patient is HBs Ag +ve with HBs Ab titer > 10 IU/L, or if the recipient is a very low risk of transmission in HBs Ab -ve recipient.
Isolated positive anti-HBc antibodies can be explained by a variety of clinical conditions, such as acute hepatitis B, cured HBV infection, declining anti-HBs titer, and false positives.
The effect of donors with positive HBc antibodies in renal transplantation seems to be minimal. According to donor and recipient immunological state, there is a moderate risk of HBV reactivation in kidney transplants, without antiviral treatment. Pre-transplant recipient HBV immunity appears to protect against de novo infection following donation of solid organs other than the liver from a core antibody positive donor.
In the first year following a kidney transplant, HBV DNA and HBsAg should be checked every three months, and then every six months. Patients with occult HBV infection should be treated similarly to those who test positive for HBsAg. One to five percent of kidney transplant recipients are thought to be at risk of HBV reactivation. Hence, prophylaxis is recommended to reduce the risk of infection reactivation. Consider prophylaxis with antiviral therapy for up to a year while also monitoring out for HBV recurrence in this donor with HBcAb positive serology. In this patient, antiviral prophylaxis with lamivudine or entecavir are indicated. So Yes, I will accept this donor.
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
Yes, I will accept the offer from an HBcAb-positive living organ donor as long as the recipient has received a successful vaccination, has an HBsAg-positive HBs Ab titer of >10 IU/L, or has a very low risk of transmission if the recipient has HBsAb-negative recipients.
In the current index case, the potential deceased donor virology screen revealed: HBsAg negative, HBsAb negative,both HBeAg and HBeAb are negative and isolated HBcAb positive. Both HCV and HIV are negative.
Basically, Hepatitis B core antibody (HBcAb) is the first antibody to appear following acute hepatitis B infection and will persist in high levels following resolution of infection and in chronically infected patients. Resolved infection is recognized by the presence of (HBsAb) in the serum.In chronic infection (HBsAg) is typically present.
Isolated HBcAb, which is defined as positive HBcAb with undetectable HBsAg and HBsAb can occurs in one of several clinical situations:
-The only marker for Acute hepatitis B infection during “window phase”.
-It can be presents between disappearance of HBsAg and appearance of HBsAb. -It can represent remote resolved infection with the decline of HBsAb to undetectable levels.
-Ongoing chronic infection with HBsAg that is undetectable, either because of low levels of HBsAg or because of mutations.
*In the current scenario, it represents prior hepatitis B infection with negative HBS Ag and HBS Abs.
The answer to the question: Yes will accept the offer. The risk of developing a de novo HBV infection after transplantation from HBcAb-positive donors may be up to 70% in liver transplant recipients, while the negative impact of HBcAb-positive donors in renal transplantation appears low to negligible. Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met? Yes ,I will accept the offer from HBcAb-positive living organ donor provided that successfully vaccinated recipient or in recipients with HBsAg-positive with HBs Ab titer >10 IU/L as well as for recipients with HBsAb-negative recipients with a very low risk of transmission.
In these patients,antiviral prophylaxis with lamivudine or, alternatively, with entecavir are indicated.
Referrences:
Fong TL, Bunnapradist S, Jordan SC, Cho YW. Impact of hepatitis B core antibody status on outcomes of cadaveric renal transplantation: analysis of United Network of Organ Sharing Database between 1994 and 1999. Transplantation. 2002;73:85–89. Veroux M, Puliatti C, Gagliano M, et al. Use of hepatitis B core antibody-positive donor kidneys in hepatitis B surface antibody-positive and -negative recipients. Transplant Proc. 2005;37:2574–75.
Patient with folloing result HBsAg negative, HBsAb negative, HBcAb positive, HBeAg and HBeAb are negative. HCV and HIV are negative.Will you accept this DBD donor;Yes i will accept his kidney
HBV DNA testing is utilized to identify occult HBV infection since a deceased donor has isolated anti-HBc in the absence of HBsAg and anti-HBs antibody.
It shows that there is very little chance of HBV transmission from kidney donors who have tested positive for HBcAb.
As a result, ESRD patients can receive kidney transplants from these donors without risk. If it is a living donor and the recipient is also HBcAb positive; Yes I will accept if the below criteria are full filled
HBV DNA viral load that has not been found in the recipient or donor to rule out occult infection
To rule out the potential of an active, ongoing infection, test for anti-HBc IgM and IgG.
Normal liver synthethetic profile including ALT, may require liver biopsy to rule out fibrosis or fibroscan.
Informed consent explaining risk of de novo and reactivation of disease and prognosis
Level of HBsAb and vaccination accordingly.
Renal grafts from anti-hepatitis B core-positive donors: a quantitative review of the literature Mahboobi N, Tabatabaei SV, Blum HE, Alavian SM. Renal grafts from anti-hepatitis B core-positive donors: a quantitative review of the literature. Transplant Infectious Disease 2012; 14(5): 445-451
Guidelines for Hepatitis B and Solid Organ Transplantation.BTS. First Edition 2018
HBsAg negative, HBsAb negative, HBcAb positive, and both HBeAg and HBeAb are negative. Both HCV and HIV are negative. Will you accept this DBD donor? Yes, I will accept .
Our deceased donor has isolated anti-HBc with the absence of HBsAg and anti- HBs antibody, thus HBV DNA testing used to diagnose occult HBV infection, and non-liver organ transplantation such as 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 (1). Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met? Yes, I will.
If recipient is HBc Ab positive and HBs Ab negative or titer less than 10è will consider vaccination, prophylaxis with high dose Immunoglobulin or Lamivudine and strict follow up by HBV PCR and liver function test.
If HBs Ab titer >10 iu/L , no need for prophylaxis and clinical follow up with HBV PCR and liver function. References:
1-Mahboobi N, Tabatabaei SV, Blum HE, et al. Renal grafts from anti hepatitis B core positive donors. A quantitative review of the literature. Transpl Infect Dis 2013; 14: 445-51.
2– British Transplantation Society Guidelines: Guidelines for Hepatitis B & Solid Organ Transplantation 2018.
3-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.
Yes, I will accept the donor because of the following reason
The kidneys from the HBcAb-positive organ donor can be used for any recipient, and the risk of de novo HBV infection is documented to be low
Scarcity of organs for donation
Kidneys from DBD have the advantage of shorter warm ischemic and are still better than for patients remaining on dialysis
Absent of co-infection with other virus-like HCV and HIV
In the above situation, the use of lamivudine for 6 months has been suggested by the BTS guidelines
Will you accept the same organ if it is a living donor and the recipient is also HBcAb positive
Yes, I will accept after the following condition is met
Undetected HBV DNA viral load in both recipient and donor to exclude occult infection
Check for anti-HBc IgM and IgG, to rule out the possibility of active ongoing infection
Liver enzymes aminotransferase
Clothing profile
Abdominal USS/ Fibroscan
Good immunological matching to avoid
Informed consent is to be obtained from the recipient explaining the type of the organ and prognosis after the kidney transplant
The recipient must agree to have the vaccination if the anti-HBs is less than 100IU/ml to boost the immunity and for a second series if there is no response in the first series of vaccination
MDT comprising of a hepatitis specialist for a detailed review of all the serology results
The persistently low-level HBV DNA in the absence of anti-HBs is a pointer to occult HBV infection.
Post kidney transplantation
Recipients with evidence of past HBV infection (HBcAb positive alone) are at risk of HBV reactivation Post-KTP and could be considered for a limited (6-12 months) course of prophylactic antiviral treatment along with monitoring for HBV recurrence.
HBV DNA and HBsAg should be monitored every three months in the first year, then every 6 months
References
Jeong Eun Song, Do Young Kim. Diagnosis of Hepatitis B. Ann Transl Med. 2016; 4(18): 338
Guidelines for Hepatitis B and Solid Organ Transplantation.BTS. First Edition 2018
Johnson, R. J, Bredbury L.L, Martin, K, Neuberger, J, Registry, U.K.T. Organ donation, and Transplantation in the UK in the last Decade: Areport from the UK National Transplant Registry. Transplantation. 2014, 97; S1-S27.
3. You were offered kidneys from a 59-year-old male DBD (donor after brain stem death) donor who suffered from SAH (grade 5) complicating cerebral aneurysm. His retrieval S Cr was 72 µmol/L. Virology was reported as follows: HBsAg negative, HBsAb negative, HBcAb positive, and both HBeAg and HBeAb are negative. Both HCV and HIV are negative.
=================================================================== History
The 59-year-old male DBD donor had 72 µmol/L of S Cr, HBsAg negative, HBsAb negative, HBcAb positive, and both HBeAg and HBeAb negative, and HCV and HIV negative.
Will you accept this DBD donor?
Yes I will accept this donor because ;-
The impact of HBcAb-positive donors in renal transplantation appears low to negligible.
Donation of non-liver solid organs from a core antibody positive donor is rarely associated with de novo infection of the recipient, and pre-transplant recipient HBV immunity appears to protect against it.
All patients being worked up for solid organ transplantation must be tested for HBsAg, HBsAb (absolute titres) and HBcAb.
All donors who are positive for HBcAb but HBsAg negative (past HBV exposure) must have HBV DNA testing to exclude the possibility of occult HBV infection.
Risk of reactivation of HBV according to donor and recipient serolog without antiviral prophylaxis/treatment is low .
Infection with isolated anti-HBc can occur in several clinical settings, including acute hepatitis B, resolved HBV infection, waning of anti-HBs titer, and false positives.
=================================================================== Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
YES I will accept this donor post evulation
Risk of HBV infection/ reactivation in non-liver SOT without antiviral prophylaxis/treatment(Moderate – high)
HBcAb positivity, with or without HBsAb, is indicative of past HBV infection and should be managed posttransplant.
Occult HBV infection should be managed in the same way as HBsAg positive patients.
Risk of HBV reactivation is estimated at 1-5% in recipients of kidney transplantation.
Organ donation from donors with previous HBV exposure is a safe way to expand the donor organ pool.
Lamivudine is the most widely used antiviral treatment for HBV naïve recipients, reducing the risk of de novo hepatitis B from 58% to 11% and 18% to 2%.
Combined therapy with HBIG has not been shown to confer additional benefit, and newer NA antivirals are less cost-effective than lamivudine in the long-term.
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
Thankyou well done for dealing with the living donation scenario differently.If RECIPIENT is HBVc positive, could be OCCULT state and should treated as HBsAg +.
Might have had a prior infection and the test was not sensitive enough to detect very low levels of anti-HBs in the serum.
Might be susceptible to a false positive anti-HBc.
Might be an undetectable level of HBsAg present in the serum, and the person is actually chronically infected.
After counseling the recipient, I will ask the hepatologist to start entecavir directly post-transplant.
Core antibody-positive donors seldom infect recipients with non-liver solid organs. Serum HBsAg seroconversion, or de novo HBV infection, is rare. (3.2%) renal transplant recipients had novel HBV serological markers, however, only four (0.28%) experienced HBsAg seroconversion. Antiviral prophylaxis is challenging to prove effective since de novo infection is rare. Pre-transplant HBV immunity may prevent de novo infection.
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
Yes, I will accept the donor after the evaluation of thehepatitis B serologic panel, LFTs, and an ultrasound abdomen.
HBcAb-positive but HBsAg-negative (past infection) transplant candidates must undergo HBV DNA and HDV serology tests to rule out occult HBV or HDV infection.
Donors with HBcAb but no HBsAg (previous HBV exposure) must undergo HBV DNA testing to rule out occult HBV infection.
If HBsAb levels are <100 IU/mL in HBcAb-positive kidney transplant patients, immunization may reduce the risk of reactivation.
Lamivudine (we are giving entecavir in our center) should be provided as a preventative measure at the time of transplantation and maintained for the rest of one’s life.
References: -Centers for Disease Control and Prevention, Hepatitis B information for health professionals: Interpretation of hepatitis B serologic test results. Available from the CDC website
Guidelines for Hepatitis B & Solid Organ Transplantation (BTS)
Yes, I will accept as he has no absolute contraindication for donation and had excellent renal function. The serology indicates past HBV infection and may be occult HBV infection
2.Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
Yes,this type of donor (HBcAb positive & HBsAg negative) can be use for any liver recipient ideally in the following order: first option for HBsAg positive recipient, second option for HBV-immune recipient and lastly for HBV non-immune recipient
Recipient should be counseled during evaluation that, He may get an organ from a donor with past HBV infection
Prevention of HBV reactivation is mandatory
Prophylactic lamivudine should be given at the time of transplantation and continued for life
This type of donor (HBcAb positive & HBsAg negative) can be use for any liver recipient ideally in the following order: first option for HBsAg positive recipient, second option for HBV-immune recipient and lastly for HBV non-immune recipient
The use of anti-HBc antibody-positive kidneys is considered a safe way to expand the donor pool as it is associated with negligible risk of transmission of HBV infection, depending on the recipient’s protective immunity status .
Causes of isolated HBcAb :
– Early window period of acute hepatitis B. – Resolved HBV infection with warning of anti-HBs titer. – A false positive anti-HBc. – An occult chronic HBV infection with low viremia and undetectable HBsAg. Kidney transplantation from anti-HBc positive donors can be performed safely without the need for prophylaxis in recipients with HBV immunity (>10 IU/mL). In patients with low titer of anti-HBs (<10 IU/mL), a pre-transplant vaccine booster should be administered and, if successful, no prophylaxis is needed. In patients not responding to vaccines, consider prophylaxis with hepatitis B Immunoglobulin or lamivudine.
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
– Yes, I will accept this donor .
Any potential transplant recipients found to be HBcAb positive but HBsAg negative (past infection) must have HBV DNA and HDV serology testing to exclude occult HBV or HDV infection. If proved no occult chronic infection and the kidney recipient is immune (anti HBs > 10 mIU/mL) , 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. if the positive recipient has low immunity (anti-HBs <10 IU/mL) prophylaxis with hepatitis B Immunoglobulin or lamivudine may be needed after a booster dose of hepatitis B Vaccine .
4.Srisuwarn P, Sumethkul V. Kidney transplant from donors with hepatitis B: A challenging treatment option. World J Hepatol 2021; 13(8): 853-867 [PMID:34552692 DOI:10.4254/wjh.v13.i8.853]
Will you accept this DBD donor? Yes, I will accept the donor.
According to
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. (1A)
When a HBcAb positive donor is used, lamivudine prophylaxis may be given for six months after transplantation, although the risk of transmission is very low. (2C)
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
This donor is HBsAg -ve, HBsAb -ve
HBcAb +ve
HBeAg and HBeAb -ve
So, this donor has either past HBV infection with no active infection at present or an occult infection.
The donor can be accepted even if recipient is HBcAb positive is when occult infection if ruled out or proper steps are taken to treat it.
So, additional tests would as below:
Any potential transplant recipients found to be HBcAb positive but HBsAg negative (past infection) must have HBV DNA and HDV serology testing to exclude occult HBV or HDV infection. (1B)
All donors who are positive for HBcAb but HBsAg negative (past HBV exposure) must have HBV DNA testing to exclude the possibility of occult HBV infection. (1C)
When a HBcAb positive donor is used, lamivudine prophylaxis may be given for six months after transplantation, although the risk of transmission is very low. (2C)
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 from a HBcAb positive donor, regardless of treatment or prophylaxis regimen. (1C)
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)
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
1-Will you accept this DBD donor? Yes; I will accept this DBD donor; According to British Transplantation Society Guidelines:March 2018; –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. (1A)
-When a HBcAb positive donor is used, lamivudine prophylaxis may be given for six months after transplantation, although the risk of transmission is very low. (2C) 2-Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met? Yes; I will accept this donor; Interpretation of current case; according his virology report HBsAG negative , HBsAB negative , HBcAB positive, HBeAG negative, HBeAb negative HCV negative , HIV negative -(This Doner has prior infection vs Ocult infection); Past HBV infection;
-Defined by the coexistence of anti-HBs and IgG anti-HBc. Occult HBV infection;
-Defined by persistence of low level of intrahepatic HBV DNA without detectable HBsAg.
-It is a serological situation defned by the presence of isolated anti-HBc with the absence of HBsAg and antiHBs antibody.
-The detection of HBV DNA in the liver is the gold standard of diagnosis for occult HBV infection, however, gaining hepatic HBV DNA is diffcult in clinical setting since the procedure is invasive. Isolated anti-HBc positive can be seen in three conditions.
*First, it can be predominantly seen as IgM class during the window period of acute phase.
*Second, after acute infection had ended, anti-HBs has decreased below the cutoff level of detection.
*Third, after several years of chronic HBV infection, HBsAg has diminished to undetectable levels.
-In these conditions, anti-HBc IgM should be checked in order to assess the possibility of recent HBV exposure. Importance of diagnosis of occult HBV infection;
-It can be transmitted via transfusion, solid organ transplantation, or hemodialysis.
-Reactivation of HBV infection may occur in patients receiving chemotherapy or immunocompromised state.
-It may accelerate liver injury and lead to hepatic fibrosis in patients with chronic liver disease including chronic hepatitis C infection.
-It appears to be a risk factor for HCC by its carcinogenic effect and by leading to continuous hepatic inflammation and fibrosis.
-What will do for acceptance this doner; -Further investigation;
(HBV DNA & Genotyping ,HDV serolog, anti HBc IM , U/S on Liver) According to British Transplantation Society Guidelines: March 2018; –Any potential transplant recipients found to be HBcAb positive but HBsAg negative (past infection) must have HBV DNA and HDV serology testing to exclude occult HBV or HDV infection. (1B) –All donors who are positive for HBcAb but HBsAg negative (past HBV exposure) must have HBV DNA testing to exclude the possibility of occult HBV infection. (1C) –Prophylactic anti viral treatment; According to British Transplantation Society Guidelines: March 2018;
-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 a limited (6-12 months) course of prophylactic antiviral treatment; although monitoring for HBV recurrence is an equally acceptable strategy. (2B) -Vaccination; According to British Transplantation Society Guidelines: March 2018; –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) -Close Monitoring after KT; According to British Transplantation Society Guidelines: March 2018;
-HBV DNA and HBsAg should be monitored every three months in the first year and thereafter every six months in individuals receiving a graft from a HBcAb positive donor, regardless of treatment or prophylaxis regimen. (1C)
-Monitoring intervals should be shortened in cases of self-reported or suspected non-adherence. (Not graded) References;
-British Transplantation Society Guidelines: March 2018.
Raimondo G, Allain JP, Brunetto MR, et al. Statements from the Taormina expert meeting on occult hepatitis B virus infection. J Hepatol 2008;49:652-7.
-Raimondo G, Caccamo G, Filomia R, et al. Occult HBV infection. Semin Immunopathol 2013;35:39-52.
-Mahboobi N, Tabatabaei SV, Blum HE, et al. Renal grafts from anti-hepatitis B core-positive donors: a quantitative. review of the literature. Transpl Infect Dis 2012;14:445-51.
-Minuk GY, Sun DF, Greenberg R, et al. Occult hepatitis B virus infection in a North American adult hemodialysis patient population. Hepatology 2004;40:1072-7.
-Yoo JH, Hwang SG, Yang DH, et al. Prevalence of occult hepatitis B virus infection in hemodialysis patients. Korean J Gastroenterol 2013;61:209-14.
Will you accept this DBD donor? Yes can accept this kidney keeping in mind patient’s isolated B core antibodies. HBc antibodies in absence of HBsAg have been reported in upto 20% [1] in endemic areas which could be due to;
· Anti HBs has fallen to undetectable level many years after recovery. · HbcAb is a false positive. · HbSAg titer is below detectable in chronic infection. · Window period of acute hepatitis. · False negative HbsAg.
Risk of HBV transmission from blood or organ donors with isolated core antibodies has been reported to be 0.4-78%. [2, 3]
Keeping all these possibilities in mind will have to explain to receipt and after consenting may proceed with transplantation and prophylactic antiviral therapy with close surveillance and treatment if infection occurs.
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
The above mentioned possibilities could be there so in case of live donor will have to do, · Repeat testing for Anti HBc IgG and IgM (to exclude active infection along with Liver enzymes), HBsAg,ant HBs, HBe antibody. · Liver function test and radiological scan to exclude chronic infection. · DNA PCR · Despite Negative DNA and no active hepatitis patient can develop de novo infection in up to 14% of liver recipients who received organ from isolated core antibody positive but negative HBsAg and negative DNA. [4] · Risk of HBV infection would be there but keeping in mind dialysis related morbidity and mortality an individualized approach should be adopt and close surveillance for HBV infection after transplantation. References
1. Lok AS, Lai CL, Wu PC. Prevalence of isolated antibody to hepatitis B core antigen in an area endemic for hepatitis B virus infection: implications in hepatitis B vaccination programs. Hepatology. 1988 Jul-Aug;8(4):766-70. doi: 10.1002/hep.1840080411. PMID: 2968945. 2. Lok AS, Lai CL, Wu PC. Prevalence of isolated antibody to hepatitis B core antigen in an area endemic for hepatitis B virus infection: implications in hepatitis B vaccination programs. Hepatology. 1988 Jul-Aug;8(4):766-70. doi: 10.1002/hep.1840080411. PMID: 2968945. 3. van de Laar TJ, Marijt-van der Kreek T, Molenaar-de Backer MW, Hogema BM, Zaaijer HL. The yield of universal antibody to hepatitis B core antigen donor screening in the Netherlands, a hepatitis B virus low-endemic country. Transfusion. 2015 Jun;55(6):1206-13. doi: 10.1111/trf.12962. Epub 2014 Dec 15. PMID: 25494685. 4. Bohorquez HE, Cohen AJ, Girgrah N, Bruce DS, Carmody IC, Joshi S, Reichman TW, Therapondos G, Mason AL, Loss GE. Liver transplantation in hepatitis B core-negative recipients using livers from hepatitis B core-positive donors: a 13-year experience. Liver Transpl. 2013 Jun;19(6):611-8. doi: 10.1002/lt.23644. PMID: 23526668.
yes professor HBV would remain in hepatocyte and de novo infection is plausible, but the point here was to highlight the importance of isolated core antibody positive associated risk.
Thank you for your input.
Will you accept this DBD donor?
Yes .
Will check Anti=Hbs titre in receipient and if >10 miu/ml then nucleotide prophylaxis is not needed post transplant.
If 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.
LFT and HBV DNA needs to be monitored every 3 monthly for a year and then yearly post transplant.
If Anti-Hbs titers <10 miu/ml then will need HBIG and post transplant nucleotide antiviral prophylaxis for 12 months .
LFT and HBV DNA needs to be monitored monthly for 3 months and then every 3 monthly for a year and then yearly.
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
Yes .
Transplant can go ahead with a single shot HBIG prophylaxis to reduce sero conversion or reactivation in a Hbc positive receipient.
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
I will accept this donor with HBCAb if it is IgG not IgM and give the recipient entacvir prophylaxis for six months
Yes.
There is sufficient evidence to provide confidence that nearly all solid organs from donors who are core antibody positive, whether HBsAg is negative or positive, can and should be used for transplantation.
Donation of non-liver solid organs from the core antibody positive donor is rarely associated with de novo infection of the recipient.
When a HBcAb positive donor is used, lamivudine prophylaxis may be given for six months after transplantation, although the risk of transmission is very low.
will l you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
Yes.
HBsAg and antibodies should be checked. also HDV for both ,Liver function test and abdominal ultrasound for both.
Antiviral should be give posttransplant.
References:
1- BTS ,Guidelines for Hepatitis B & Solid Organ Transplantation, 2018.
This donor can be gladly accepted as the core antibody when only positive while other HBV antibody screening are negative, it is then indicative of proper immune system which succeeded to eliminate this infection.
Considering the recipient status HBcAb positivity, further HBV profile screening is required.
HBV nucleic acid assessment by PCR, besides HDV to rule our HDV co-infection.
Other hepatropic 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 LFTs, 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.
Can this DBD be accepted? The donor is a donor after brain death with good renal function….The donor is HBcAb positive…Other serological tests for Hepatitis B infection are negative….HbsAg, HbeAg HBeAb and HIV,HCV are negative….Positive Anti HBcAb signifies either a past infection or a resolving infection…
As per the BTS guidelines, kidneys from HBcAb positive donors can be used for any recipients…The risk of de novo Hepatitis B infection in recipient is low….
As this is a cadaver renal donor we will be able to directly transplant the organ without evaluating the donor further….
The recipient should have finished primary immune – prophylaxis’s with Hepatitis B vacccine..If the recipient is immune (anti HBs titire >10 IU/ml), there is no need of anti viral prophylaxsis and regular monitoring of the HBV DNA viral load post transplant is indicated at 7 days, 14 days and 21 days and monthly for 3 months…If the recipient is not vaccinated and is not immune (anti HBs titre <10 mIU/ml), the recipient has to be treated with anti virals namely lamividine or tenofovir for 6months after transplant
If this was a live donor renal transplant?
A HBcAb positive live donor can be accepted for a recipient who is HBcAb positive…the donor and the recipient have to be evaluated in detail….it is important to do a detailed evaluation for the donor…the donor should be screened to rule out cirrhosis of the liver HBV DNA testing of the donor is needed, so as OGD, fibroscan of the donor it could be a past infection with underlying cirrhosis.
The recipient is also core antibody positive indicating past infection of chronic Hepatitis B infection….other markers like HbsAg, anti HBsAg, HBeAg and HBV DNA should be done…HDV RNA PCR to rule out co infection should also b done…We should do LFT , PT INR of the recipient with OGD and fibroscan of the liver to rule of fibrosis…. If cirrhosis is ruled out we can proceed for renal transplant alone…If the recipient is HBcAB positive and Anti Hbs Titre < 100 IU/ml, vaccination should be considered for the recipient o boost the titres….the AST recommends no need prophylaxis with antivirals for those vaccinated with HBV vaccine and good anti HBs titre….
If the recipient is highly immunosuppressed then anti viral prophylaxis’s is indicated if the use of ATG, Plasma and rituximab, or of rising serial titres of HBV DNA after transplant is demonstrated…
● Will you accept this DBD donor?
☆ Yes . I will accept him .
☆ Solid organ transplant recipients of HBcAb-positive organ donors, exposed to immunosuppression, may have a higher risk of developing de novo HBV infection after transplantation.But it’s impact in renal transplantation appears low to negligible.
☆ The risk may be more accurately determined by measuring HBV-DNA than HBcAb, HBcAb-positive HBV-DNA negative donors are unlikely to transmit infection to recipients.
● Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
☆ In the context of living donation, donors who are HBcAb alone (with negative HBsAg and undetectable DNA in blood) can therefore donate. The prospective recipient will ideally have been effectively immunised against HBV,
☆ Although immunization can be repeated post-transplant if a suboptimal antibody
response has been made. The addition of anti-viral drugs may be considered, especially in recipients with a low HBsAb response to vaccination.
☆ Strict surveillance serologies are mandatory and an HBIg single-shot prophylaxis may reduce the risk of HBV seroconversion or reactivation in all naïve or HBcAb-positive transplant recipients.
References:
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.
Is it safe to accept kidney from hep c antibodies positive patient
Yes, as it reflect previous infection, with close monitoring
Q1: Yes, I would accept conditions with isolated HBC AB positivity includes: previous infection (if HBC AB IgG is positive), window phase (if HBC AB IgM is positive), occult infection (if HBC DNA is positive), or passive transfer of this Ab by transfusion. Hence, a history of transfusion, IV abuse, previous hepatitis B, or exposure to it, should be taken after TX, prophylaxis is necessary and associated with close monitoring.
Q2: for live donation, more investigations are needed before transplantation such as HBV DNA, in both recipient and donor. In addition, HBC Ab in recipients with HBV DNA simultaneously shows the carrier state of the recipient and needs lifelong prophylaxis with entecavir or tenofovir alafenamide.
Reference:
Malinis, M., & Boucher, H. W. (2019). Screening of donor and candidate prior to solid organ transplantation—Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clinical Transplantation, 33(9). https://doi.org/10.1111/ctr.13548
Will you accept this DBD donor?
· I will accept this DBD donor as the risk of de novo HBV infection is low. The BTS guidelines stated that kidneys from HBcAb positive donors can be used for any recipient. However, a heptologist should be involved as part of the MDT and during the follow-up and the recipient should receive proper counselling.
· Administration of Lamivudine prophylaxis to the recipient depends on the recipient HBV immune status. If the recipient is HBV immune (anti-HBs +), no need for prophylaxis. Otherwise, administer 6 months Lamivudine prophylaxis.
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
· Yes. HBcAb + live donor can be accepted for HBcAb+ recipient.
· The donor should be assessed by:
· Liver function tests
· Check the type of HBcAb (IgG or IgM)
· HBV-DNA to exclude occult HBV infection
· Abdominal US
· The recipient should be assessed by: checking other serological markers including HBsAg, HBsAb, HBeAg, HBeAb, and HBV DNA by PCR as well as HDV to rule our HDV co-infection.
· Antiviral prophylaxis with tenofovir or entecavir can be given as this recipient is only HBcAb positive.
· Regular post-transplant monitoring of LFTs, HBsAg and HBV DNA should be done every 3 months in year 1 and during periods of intense immunosuppression.
References:
1. Ouseph R, Eng M, Ravindra K, Brock GN, Buell JF, Marvin MR. Review of the use of hepatitis B core antibody-positive kidney donors. Transplant Rev (Orlando). 2010 Oct; 24(4):167-71.
2. Guidelines for Hepatitis B & Solid Organ Transplantation. British Transplantation Society Guidelines, 2018.
Regarding his virology profile yes, I will accept him . after satisfying routine immune matching.
According to current guidelines, there is an increasing trend of accepting non-liver organs from total hepatitis B core antibody-positive [anti-HBc (+)] donors to be used in any recipient regardless of HBV immune status without prophylaxis due to the negligible risk of de novo infection.
Although some studies mentioned that despite the low risk of transmission is very low, lamivudine prophylaxis may be given for 6 months after transplantation, when a HBcAb positive donor is used.
In acute hepatitis B infection, immunoglobulin M (IgM) antibody to hepatitis B core antigen (IgM anti-HBc) becomes positive after 4 wk to 6 wk of exposure indicating recent infection and active viral replication whereas total hepatitis B core antibody (anti-HBc) appear at the onset of symptoms and persists for life.
In clinical practice, isolated anti-HBc is commonly observed. This may occur in several clinical settings.
First, the early window period of acute hepatitis B.
Second, a resolved HBV infection with waning of anti-HBs titer.
Third, a false positive anti-HBc. This setting is commonly found in an area with a low prevalence of HBV infection.
Fourth, an occult chronic HBV infection with low viremia and undetectable HBsAg. The latter can occur with a poor test quality or when there is a mutation of HBsAg
Condition that should be met.
–full virology profile for recipient ,If recipient HBsAg & HBV DNA is negative then vaccination of the recipient.
– Monitoring for HBV Infection; HBV DNA and HBsAg should be monitored every 3 months in the first year reference
Praopilad Srisuwarn and Vasant Sumethkul .Kidney transplant from donors with hepatitis B: A challenging treatment option World J Hepatol. 2021 Aug 27; 13(8): 853–867
will you accept this DBD donor?
I will accept the donor
ill you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
yes i will accept as the risk of deactivation is low
Will you accept this DBD donor?
Yes
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
yes,I will accept ,but there is risk of reactivation of virus. Recipient HbsAg status should be checked.,Because in case of HbsAg positive risk of reactivation is highest.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. Among HBsAg-negative patients, reactivation is defined by the appearance of HBV DNA or the reappearance of HBsAg.Prior infection(Anti HBc antibody positive) is not a containdication to transplantation.Recipients who are anti-HBc positive have evidence of prior infection and need antiviral therapy to prevent HBV reactivation secondary to immunosuppressive therapy. The presence of anti-HBs at time of transplantation may not prevent reactivation, because anti-HBs titer can decrease and become undetectable with immunosuppression.The duration of antiviral therapy can vary. Some centers administer antiviral therapy indefinitely to all recipients with prior HBV. Others discontinue treatment when immunosuppression is reduced to low-dose maintenance level and monitor closely thereafter, unless the patient is receiving immunosuppression with an agent associated with a high risk of HBV reactivation (eg, rituximab).
Monitoring/management of reactivation
What to monitor – The approach to monitoring for HBV reactivation or flare depends upon whether the recipient is receiving preventive antiviral therapy and/or the type of immunosuppressive regimen that is used:
Recipients on antiviral therapy – Recipients receiving antiviral therapy to prevent reactivation or flare should have serum aminotransferases and HBV DNA monitored every six months or more frequently as indicated.
If antiviral therapy is discontinued, we monitor liver chemistries, HBV DNA, and HBsAg at least once every three months for at least one year.If reactivation occurs, patients should resume antiviral therapy
Yes, iwould accept this DBD donor
Yes i accept this donor as a live donor.
If the recipient HBsAg negative but Anti HBs positive then risk of HBV reactivation is low to moderate. But the risk is moderate to high if the recipient HBsAg & Anti HBs both are negative. The risk is very high if recipient’s HBsAg positive.
Condition that should be met:
– Detail virological study of the recipient.
– If recipient HBsAg, HBeAg & HBV DNA is negative then vaccination of the recipient.
– Target antiviral treatment & prophylaxis should be given according to HBV status
Yes , I would receive this patient . Patient without serology indicative of replication, so this result represents a criterion for curing the disease.
To prove that there is no replication, HBV DNA PCR could be used.
Yes, but the recipient should be further evaluated for the existence of liver disease at this time and monitored every 3 months with the test of HBsAg and HBV DNA for at least 1year post-transplant. In addition to performing prophylaxis treatment with entecavir or tenofovir
Will you accept this DBD donor?
Yes, I will accept this donor if no other choice are available, but the recipient should be vaccinated and maintained on antiviral therapy for 6 months with regular follow up for graft function and HBV DNA PCR .
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
Yes I will accept this donation but first we must assess both the donor and recipient by doing HBV DNA PCR, HBsAg , anti-HBc IgM &IgG, HDV serology , Abdominal US, LFT, and we need to check anti-HBC level in recipient if less than 100 we must give vaccination and HB IG with antiviral prophylaxis for 6 months.
Reference
BTS guidelines 2017.
Will you accept this donor?
Yes, kidneys from a HBcAb positive organ donor can be safely used, as the risk of HBV transmission is low.
· Anti-HbcAb is positive if the patient has resolved or resolving hepatitis B infection, or during window phase in which HbsAg is not detectable – HBV DNA PCR can detect occult infection
· The recipient should have been vaccinated with HBV.
· Recipient should be explained about need monitoring or antiviral prophylaxis after transplant for at least 06mths.
Will you accept this donor as a live donor if the recipient is also HBcAb positive?
If yes, what are the conditions that should be met–
Anti-HBcAb positive live donor can also be accepted
– unless there is a positive HBcAb-IgM or positive HBV DNA
Further investigations like HBV DNA PCR, anti-HbcIg M and IgG, LFT, USG abdomen, HDV serology of both donor and recipient should be done.
– Recipient’s anti-Hbs Ab needs to be tested – if <10 IU/ml, restart HBV vaccine 4 doses
– Recipient should receive antiviral prophylaxis with either entecavir or tenofovir
– close monitoring of graft function and regular test of HBsAg and HBV DNA every 3 months for at least 1year post-transplant.
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. Int med journal of experimental and clinical research. 2016 Apr 28; 22: 1427-34. PMID: 27123988. Pubmed Central PMCID: PMC4915324. Epub 2016/04/29. eng.
3. Srisuwarn P, Sumethkul V. Kidney transplant from donors with hepatitis B: A challenging treatment option. World J Hepatol 2021 Aug 27; 13(8): 853-67. PubMed PMID: 34552692. Pubmed Central PMCID: PMC8422915. Epub 2021/09/24. eng.
4. 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 May; 15(5): 1162-72. PubMed PMID: 25707744. Epub 2015/02/25. eng
Yes, I will accept this living donor with anti HBc Ab.
Those patients who are Anti-HBc antibody positive and HBsAg negative should not be excluded from transplantation.
Those patients who are Anti-HBc antibody positive and HBsAg negative should not receive antiviral prophylaxis as the risk of reactivation is low. Patients who are Anti-HBc antibody positive and HBsAg negative should be monitored for a minimum of one year post transplantation by monitoring of HBsAg and HBV DNA. If the donor has chronic Hep B infection, then the recipient should receive prophylaxis with lamuvidin for 1 year.
Will you accept this DBD donor?
Anti-Hbc positivity means either the patient has resolved or resolving hepatitis B infection,or the patient has False-positive anti-HBc, or the patient is in window phase in which HbsAg is not detectable and PCR for HBV DNA to be done to check for acute infection
Yes, this donor can be accepted if no other donor available but the recipient should be vaccinated and placed on antiviral prophylaxis after transplant for at least 06mths and all risks explained to the recipient.
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met–
In this case, donation can be accepted but before that investigations like PCR for HBV DNA , anti-HbcIg M and IgG, LFTs ,USG abdomen ,HDV serology of both donor and recipient should be done. Anti-Hbs of the recipient should also be done. Recipient should be vaccinated if anti-Hbs titer less than 100 and also placed on antiviral prophylaxis post-transplant with close monitoring of graft function and regular test of HBsAg and HBV DNA 3 monthly for at least 1 year post-transplant.
REFERENCES:
1- British Transplantation Society Guidelines: Guidelines for Hepatitis B & Solid Organ Transplantation 2018
The patient received DBD from an HBcAb positive Donor.
Where donor is HBcAb positive. Other serological tests (HBsAag, HBeAg, HBeAb, HIV and HCV) are negative.
HBcAb results from resolving infection or a low level of chronic infection.
I shall accept this donor as risk of transmission is low
The decision of using antiviral prophylaxis is according to the immunity status of the recipient
If HBsAg is positive (immunized recipient) then no need for antiviral
If negative then we shall use antiviral e.g Lamivudine for 6 months
In case of isolated HBcAb then we shall do PCR test to detect viral load
As well as liver function tests and Ultrasound liver.
Recipient should be detected for HBV markers and liver function tests.
And check the vaccination status if below the 100 IU per ml then a booster dose should be indicated.
In our case donor Has HBcAb positive and also HBcAb is positive in recipient
So antiviral prophylaxis would be required.
In addition to vaccination of the recipient and consulting a hepatologist.
And regular check for HBV PCR as well as liver function tests and Ultrasound.
Yes, I will accept this living donor with anti HBc Ab.
Those patients who are Anti-HBc antibody positive and HBsAg negative should not be excluded from transplantation.
Those patients who are Anti-HBc antibody positive and HBsAg negative should not receive antiviral prophylaxis as the risk of reactivation is low. Patients who are Anti-HBc antibody positive and HBsAg negative should be monitored for a minimum of one year post transplantation by monitoring of HBsAg and HBV DNA. If the donor has chronic Hep B infection, then the recipient should receive prophylaxis with lamuvidin for 1 year.
Will you accept this donor? (1-3)
– yes, I would
– kidneys from a HBcAb positive organ donor can be used on any recipient since the risk of de novo HBV infection is low so is the risk of HBV transmission
– unless there is a positive HBcAb IgM or positive HBV DNA
– however, the recipient should receive antiviral prophylaxis with either entecavir or tenofovir
– HBIG can be considered if there is no response to antiviral therapy
References
1. Veroux M, Ardita V, Corona D, Giaquinta A, Ekser B, Sinagra N, et al. Kidney Transplantation From Donors with Hepatitis B. Medical science monitor : international medical journal of experimental and clinical research. 2016 Apr 28;22:1427-34. PubMed PMID: 27123988. Pubmed Central PMCID: PMC4915324. Epub 2016/04/29. eng.
2. 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.
3. 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
Yes,I will accept especially if the HBV DNA is negative with a close follow up and observation
references
BTS
DBD with this serology suggest PAST INFECTION with HBV
We can accept kidney with possibility of reactivation of this infection in recipient depending on his/her serology of HBV as follow
LOW RISH – NEGATIVE SEROLOGY
HIGH RISK- SEROLOGY SUGGESTIVE OF PAST INFECTION like CORE ANTIBODY
VERY HIGH RISK- ACTIVE OR RECENT INFECTION SEROLOGY LIKE HBsAG and HBeAG OR AB positive
LAMIVIDIN for 6 months is drug of choice
. Potential donor with positive HBcAb and negative HBsAg can be accepted for any recipient with low risk regarding de novo HBV infection. Donor can accepted with 6 months of lamuvidin for prophylaxis post transplantation.
It depends on HBV immune status of the recipient to explore risk of transmission or reactivation of the viral B infection.
HBsAg-ve/ HBsAb-ve denotes low to moderate risk
Hb cAb positive and HbsAb -ve denote moderate to high risk.
HBsAg+ve/ HbcAb+ve denotes very high risk
Donor HBV DNA quantification is needed to rule out occult infection.
Live donor can be accepted with excluding of occult infection in donor in low risk recipient
Reference:
BTS guidelines for Hepatitis B & Solid Organ Transplantation,2018.
· Will you accept this DBD donor?
These donors have been exposed to hepatitis B in the past but test negative for the more serious hepatitis B surface antigen. In clinical practice, isolated anti-HBc is commonly observed. This may occur in several clinical settings. First, the early window period of acute hepatitis B. Second, a resolved HBV infection with waning of anti-HBs titer. Third, a false positive anti-HBc antibodies.
According to current guidelines, there is an increasing trend of accepting non-liver organs from total hepatitis B core antibody-positive [anti-HBc (+)] donors to be used in any recipient regardless of HBV immune status without prophylaxis due to the negligible risk of de novo infection.
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
· Yes, especially if recipient has good antibody titer and negative HBV DNA.
· References:
1-World J Hepatol. 2017 Sep 8; 9(25): 1054–1063. Published online 2017 Sep 8
Yes, I would accept the organ.
Since he is a deceased donor and there will be a need for triple immunosuppression, including corticosteroids, he would proceed with prophylaxis for twelve months with Tenofovir alafenamide (TAF) or Entecavir.
Will you accept this DBD donor?
This DBD donor may be accepted for renal transplantation.
Since HBsAg, HBsAb, HBeAg, HBeAb, HIV and HCV all are negative and the donor is HBcAb positive, it interprets to either a resolving acute infection (where Anti HBc IgM is positive), or a resolved HBV infection (where Anti HBc IgG is positive), or a low level chronic infection (where HBV DNA by PCR is positive).
Since the infection is resolving or has resolved or is a low grade infection, the risk of de novo HBV infection is low and prophylaxis with Lamivudine for 6 months post-transplant may be given to the recipient if the recipient has low Anti-HBs Ab titres. If the recipient has is HBV immune and has Anti-HBs Ab titres > 100 IU/L, then there is no need of antiviral prophylaxis.
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
Yes, this live donor may be accepted for renal transplantation to a HBcAb positive recipient, provided the following conditions are met.
Conditions for Donor:
Conditions for Recipient:
In conclusion, the recipient cannot be transplanted during the period of active hepatitis infection. He may undergo transplantation if he is currently immune due to a past acute infection. He may also get transplanted with prophylactic measures, if he has a low level chronic infection with adequate counselling regarding risks of acute flares during immunosuppression.
References:
British Transplantation Society. Guidelines for Hepatitis B and Solid Organ Transplantation, 1st ed.; British Transplantation Society: Macclesfield, UK, 2018
Ouseph R, Eng M, Ravindra K, Brock GN, Buell JF, Marvin MR. Review of the use of hepatitis B core antibody-positive kidney donors. Transplant Rev (Orlando). 2010 Oct;24(4):167-71. doi: 10.1016/j.trre.2010.05.001. Epub 2010 Jul 23. PMID: 20655722.
Will you accept this DBD donor?
this patient offered graft from DBD and his virology screening showed HBcAb positive so further assessment should be done as HBcAb maybe related to old resolved infection or recent infection in window phase
HBV PCR should be done if negative it means old resolved infection, if positive it means recent infection in window phase.
HDV PCR also is needed and if positive organ better to discarded.
according to British society of organ transplantation organ of HBVcAb positive donor can be retrieved as kidney is like liver and not exposed to latent HBV infection
So, I will accept this potential donor but recipient immune state is important to decide the need for antiviral prophylactic if the antibodies titter more than 100iu/ml so no need for antiviral prophylactic but if below 10iu/ml so antiviral prophylactic for 6m is needed.
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
two main differences in the scenario
1-donor is alive so if HBV PCR positive he is exposed to complication including GN and donation should be delayed until proper treatment with sustained viral response then he should be reevaluated for donation.
2-reicient is also HBcAb positive so he is natural immune with risk of reactivation if the patient planned to receive heavy induction or desensitization so prophylactic treatment should be given.
References:
Yes ,,,,
There are a substantial number of reports of kidneys transplanted from HBsAg negative/DNA undetectable, HBcAb positive deceased donors in which there have been a low risk of HBV seroconversion and no excess risk of graft failure or shortterm morbidity .
Yes,,,,
All prospective living donors should be tested for both Hepatitis B surface antigen (HBsAg) and Hepatitis B core antibody (HBcAb). If the HBcAb is positive, the donor should be tested for the presence of HBV DNA and Hepatitis B surface antibody (HBsAb). If HBsAb is >100 iU/L and HBV DNA is not detected, the infectious risk of the donor is low.
Living donors who are HBcAb alone with negative HBsAg and undetectable DNA in blood) can therefore donate. The prospective recipient will ideally have been effectively immunised against HBV, although immunization can be repeated post-transplant if a suboptimal antibody response has been made. The addition of anti-viral drugs may be considered, especially in recipients with a low HBsAb response to vaccination. Under these circumstances, advice from specialists with appropriate expertise should be sought and the donor and recipient should be fully informed.
When a HBcAb positive donor is used, lamivudine prophylaxis may be given for six months after transplantation, although the risk of transmission is very low.
Any potential transplant recipients found to be HBcAb positive but HBsAg negative (past infection) must have HBV DNA and HDV serology testing to exclude occult HBV or HDV infection.
All donors who are positive for HBcAb but HBsAg negative (past HBV exposure) must have HBV DNA testing to exclude the possibility of occult HBV infection.
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.
All prospective solid organ transplant recipients should receive a high-dose, accelerated vaccine schedule.
In those who fail to respond to the initial HBV vaccination schedule, a second series should be administered.
DD with anti-HBC positive (prior infection) the risk of transmission is negligible unless the donor is HBV DNA positive, in which case prophylactic antiviral therapy is recommended for one year, including entecavir and tenofovir
hepatitis BcAb in both donor and recipient means prior infection .recipient who has anti-HBc positive, HBV reactivation may occur secondary to immunosuppression therapy.
the presence of antiHBs at the time of Transplant may not prevent reactivation because anti -HBs titer can decrease and become undetectable with IS.
duration varies some give antiviral therapy indefinitely to all recipients with prior HBV.
others discontinue treatment when IS is reduced to a low maintenance level and monitor closely thereafter unless the patient receiving IS with an agent associated with a high risk of HBV reactivation (e.g rituximab)
references
update
· Will you accept this DBD donor?
Yes , I will as this donor has excellent graft function and positive Anti HBV c Ab while all other serology negative corresponds with
-Past HBV infection .
-Occult HBV infection requiring further confirmation with HBV quantitative DNA PCR .
– Assessment of risk of HBV infection in thisdonor is needed incuding history of previus blood transfusion .
As the risk of acquiring HBV infection in HBs Ag –ve/ HBc Ab + ve donor ranges 0-5% ,so dueto shortage of donor pool , donors with previous HBV infection could be accepted.
· Will you accept this donor as a live donor if the recipient is also HBcAb positive?
Yes, I will
· If yes, what are the conditions that should be met?
– Assess risk of HBV reactivation depending on presence of positive HBs Ag , HBV DNA PCR .
– Evaluate liver function to exclude decompensated LCF.
– Exclude presence of other viral hepatitis as HEV , HDV.
– Regularly monitor liver function to detect HBV reactivation early with HBs Ag and HBc Ab every 3 months and HBV DNA PCR every 6 months.
– Start HBV treatment at time of transplantation with lamivudine ,entecavir or tenofovir.
– Use the lowest possible dose of IS drugs needed to prevent rejection and try to early withdraw steroidtreatment or lower it to 5 mg daily.
Ref:
1- Guidelines for Hepatitis B & Solid Organ Transplantation First Edition March 2018 .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
2- Fabrizio F, Bunnapradist S, Martin P. Transplanting kidneys from donors with prior hepatitis B infection: one response to the organ shortage. J Nephrol. 2002 Nov-Dec;15(6):605-13. PMID: 12495272.
Yes will accept this donors.
Organs from anti-HBc+ donors should be considered for all adult transplant candidates after an individualized assessment of the risks and benefits and appropriate patient consent.
Indefinite antiviral prophylaxis is recommended in liver recipients with no immunity or vaccine immunity but not in liver recipients with natural immunity.
Antiviral prophylaxis may be considered for up to 1 year in susceptible non-liver recipients but is not recommended in immune non-liver recipients.
Although no longer the treatment of choice in patients with chronic HBV, lamivudine remains the most cost-effective choice for prophylaxis in this setting.
References:
1-S Huprikar , L Danziger-Isakov, J Ahn, et al. Solid organ transplantation from hepatitis
B virus-positive donors: consensus guidelines for recipient management .Epub 2015 Feb
23.
3. You were offered kidneys from a 59-year-old male DBD (donor after brain stem death) donor who suffered from SAH (grade 5) complicating cerebral aneurysm. His retrieval S Cr was 72 µmol/L. Virology was reported as follows: HBsAg negative, HBsAb negative, HBcAb positive, and both HBeAg and HBeAb are negative. Both HCV and HIV are negative.
Issues/ concerns
– 59yo, male, DBD, Grade 5 SAH complicating cerebral aneurysm
– sCr 72
– virology screen: – HBsAg negative, HBsAb negative, HBcAb positive, HBeAg negative, HBeAb negative, HCV negative, HIV negative
Will you accept this DBD donor? (1-3)
– yes, I would, due to the growing demand for organ donors this donor may still be a safe option
– a positive HBcAb result indicates a past or current infection
– HBcAb does not confer any protection against HBV
– since the donor was HBsAg negative and HBsAb negative, he could be infected, susceptible or have a resolved infection
– the kidneys from a HBcAb positive organ donor can be used on any recipient since the risk of de novo HBV infection is low
– however, the recipient should receive antiviral prophylaxis
– four possible interpretations for a state of isolated HBcAb (i.e., HBsAg negative, HBcAb positive, HBsAb negative): –
– presence of HBV DNA, HBsAg, HBeAg are markers of active infection
– IgM anti-HBc (IgM HBcAb) is a marker of acute or reactivated infection
– HBsAb is a marker of immunity
Will you accept this donor as a live donor if the recipient is
also HBcAb positive? If yes, what are the conditions that should be met? (1-3)
Issues/ concerns
– living donor who is HBsAg negative, HBsAb negative, HBcAb positive, HBeAg negative, HBeAb negative, HCV negative, HIV negative
– recipient – HBcAb positive
– HBcAb positive is suggestive of prior infection
– the goal of care among recipients with prior or chronic HBV infection is to prevent HBV reactivation and worsening of liver disease
– generally, recipients with prior or chronic HBV infection can receive a kidney transplant from any donor regardless of the donor’s HBV status; however, they should be offered antiviral therapy to prevent reactivation which may occur secondary to immunosuppressive therapy
– for recipients with prior infection (HBsAg negative and HBcAb positive): – the preferred antiviral therapies include entecavir and tenofovir (preferably tenofovir alafenamide as opposed to tenofovir disoproxil fumarate)
– the antiviral therapy should be initiated at the time of transplantation, the duration of use varies i.e., some experts give it indefinitely while others discontinue it once the immunosuppression has been reduced then they monitor the patient closely
– for recipients with chronic HBV infection (HBsAg positive and HBcAb positive): – to prevent reactivation, all recipients with chronic HBV infection should receive antiviral therapy (entecavir and tenofovir alafenamide) indefinitely, the agent chosen depends on the patients’ prior antiviral history
– the goal of treatment in chronic HBV patients is virologic suppression
– monitoring and management of reactivation: –
References
1. Veroux M, Ardita V, Corona D, Giaquinta A, Ekser B, Sinagra N, et al. Kidney Transplantation From Donors with Hepatitis B. Medical science monitor : international medical journal of experimental and clinical research. 2016 Apr 28;22:1427-34. PubMed PMID: 27123988. Pubmed Central PMCID: PMC4915324. Epub 2016/04/29. eng.
2. 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.
3. 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.
HBsAG – NEG
HBsAB – NEG
HBcAB – +VE
Isolated HBcAB
Possible scenarios;
I will accept the donor as he is low risk but then rule out false positive in donor by a pepeat assay and equally do HBV DNA in donor to rule out an occult infection. As for the recipient we will need a full screen to establish status and rule out an occult infection; HBsAG, HBsAB, HBeAG and HBV DNA,. We would then monitor LFTS,HBV DNA and HBsAG at 1 month, then every 3 months and treat HBV if reactivation occurs post transplant.
REF;
BTS Guidelines.
Yes I will accept this donor because presence of HbcAb positive means previous infection and past vaccination
In this situation need further investigation before transplant from HBV DNA, HbsAg and HbsAb to role out occult hepatitis B infection
HBcAB positivity with anti-Hbs positivity means previous infection and immunity, but here we may have an occult infection, and we need the HBV-DNA. as this is an emergent situation, not to waste the donor’s kidneys, I accept the patients with the support of anti-HBV treatment and HBV Immunoglobuline just as I accept HBsAg positive and consult a gastroenterologist or infectious diseases after detection of HBV DNA and I will repeat the HBV DNA and serology later
Will you accept this DBD donor?
In this case HBcAb is positive and HBsAg negative, HBsAb negative are negative.
Positive HbcAb can be due to previous immunity , seroconversion / Acute phase window, occult infection or false positivity.
HBeAg and HBeAb are negative , so HEV infection is ruled out.
Next step would be to check HBV DNA levels.
Yes I will accept this DBD donor.
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
Both donor and recipient are HbcAb positive . This will require further testing. HBV DNA titres should be checked.
HBsAb Titres > 10 IU/L are protective if donor is HbcAb positive. If recipients has both HBsAg and HBsAb positivity , the he is a carrier. So in conclusion if both donor and recipient are HbcAb positive then both should be screened.
👉I will accept the deceased donor, as Postive anti HB C IgG means old infection with very low risk of transmission, however, prophylactic lamivudine for 6 months can be used.
👉 If he is live donor,
_ serological testing for the recipient by HBsAg, anti HBs IgM and IgG, HBc IgM and IgG, if any antibody postive …do HBV PCR.
_exclusion of occult infection in the live donor by HBV PCR is essential before accepting him as donor as there is risk of transmission.
Will you accept this DBD donor?
Yes, if recipient is immune either by natural infection or by vaccination and has protective anti HBs antibody
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
No, not straightaway.
if recipient is HBsAg negative, HBV DNA negative and is then vaccinated. Once protective anti HBs antibody develop after vaccination then transplantation can be considered
1- Yes
2- For live donor:
HBsAg negative, HBsAb negative, HBcAb positive, HBeAg negand HBeAb negative. Both HCV and HIV are negative.
Yes I will accept this DBD
It is a case of accult infection if the HBV DNA is negative
The
Yes we will accept this donor but also we should perform HBV DNA
In the condition of , we should study the recipient serological tests
HBeAG,
HBeAB,
HBsAG,
HBsAB,
and HBV DNA
Thanks, All
I would answer the question in one line.
It is safe to accept a kidney from an HBcAb-positive patient.
Yes if anti-HBc IgG positive not IgM which indicates previous exposure with a good immune response if HBs AB positive and low risk of reactivation
Yes, the recipients will require prophylactic therapy for 6 months.
HBcAB positivity with anti-Hbs positivity means previous infection and immunity, but here we may have an occult infection, and we need the HBV-DNA. as this is an emergent situation, not to waste the donor’s kidneys, I accept the patients with the support of anti-HBV treatment and HBV Immunoglobuline just as I accept HBsAg positive and consult a gastroenterologist or infectious diseases after detection of HBV DNA and I will repeat the HBV DNA and serology later
Yes, with pre-emptive antiviral therapy, and regular monitoring
DD with anti-HBC positive (prior infection) the risk of transmission is negligible unless the donor is HBV DNA positive, in which case prophylactic antiviral therapy is recommended for one year, including entecavir and tenofovir
Will you accept this donor? (1-3)
– yes, I would
– kidneys from a HBcAb positive organ donor can be used on any recipient since the risk of de novo HBV infection is low so is the risk of HBV transmission
– unless there is a positive HBcAb IgM or positive HBV DNA
– however, the recipient should receive antiviral prophylaxis with either entecavir or tenofovir
– HBIG can be considered if there is no response to antiviral therapy
References
1. Veroux M, Ardita V, Corona D, Giaquinta A, Ekser B, Sinagra N, et al. Kidney Transplantation From Donors with Hepatitis B. Medical science monitor : international medical journal of experimental and clinical research. 2016 Apr 28;22:1427-34. PubMed PMID: 27123988. Pubmed Central PMCID: PMC4915324. Epub 2016/04/29. eng.
2. 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.
3. 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
Yes and consider six months of prophylaxis.
YES with regular monitoring and prophylactic therapy of 6 months
Isolated HBcAb positive explanations:
this case scenario require more information about any blood transfusion, previous infections, exposure to HBV cases, drug abuser ,……etc
this case less likely to be occult infections as HBeV Ag & Ab negative
this case need HBV DNA before final decision
yes i accept this case because categorized as low risk if previously infected , with close monitoring +/- lamivudine prophylaxis
Thanks, Delshad
Well done
I would accept this donor as the risk of de novo infection is low. HBcAb positive with negative HBsAg would suggest a previous infection, passively acquired antibodies from blood transfusion, acute hepatitis B infection or a false positive. It is important to get a history of any previous blood transfusion. The recipient may be offered lamivudine prophylaxis for 6 months after transplantation, although the risk of transmission is low
A HBcAb in the recipient will need to be investigated before transplantation. A careful history should be sought for any blood transfusion, risk factors for hepatitis B, testing for the full serological hepatitis B profile and the hepatitis B viral DNA. The risk of reactivation post transplant is estimated to be 1-5%. The recipients can either receive prophylaxis with lamivudine post transplant or can be floored up closely and monitored for reactivation
Guidelines for Hepatitis B and Solid Organ Transplantation, First Edition. British Transplantation Society
I note that you have explained how a donor with evidence of past infection of HBV in relation to the decision -making necessary for transplantation.
What is your logic for HBcAb in recipient?
Does it confer protection?
Thank you Professor Sharma
The presence of HBcAb alone does not confer protection. It is the presence of HBsAb more than 10 iU/ml that confer protection
The importance of HBcAb is the possibility of an occult infection
Will you accept this donor?
DBD with HBcAb positive and negative HBsAg and HBsAb.
Positive core antibody alone could occur from acute infection in the window phase, past infection or occult infection.
Hence in this donor it is important to get additional history on blood transfusion and any history of past Hepatitis B infection.
Additional test on NAAT for Hepatitis B and hepatitis D.
Yes I will accept this donor because the risk of de-novo infection in non-liver SOT is low.
Will you accept this donor if LDD and recipient also HBcAb positive?
If yes, what conditions should be met?
Both donor and recipient are HBcAb positive, additional information of the recipient would be required.
Recipient HBsAg, HBsAb and HBV and HDV DNA.
HBsAb titers >10IU/L are considered to be protective for recipients receiving from HBcAb positive donors.
The recipients HBV DNA should be low or undetectable.
Recipient with high viral load will require entecavir/ tenofovir alafenamide prior to transplantation.
Yes I will accept this donor.
Recipient with high risk of reactivation will require lamivudine prophylaxis for 6 months post transplantation.
References
Guidelines for Hepatitis B & Solid Organ Transplantation First Edition March 2018
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
Thankyou,agree that in the second part of the scenario the recipient has to undergo tests to exclude OCULLT HBV
Mainly HBV DNA.
If the recipient has as well HBsAb so this incurs immunity.
If the the R has both HBs Ag+ and HBs Ab+ then he is a carrier.
Conclusion if this is LD with only HBc Ab + for both D and R the virology screen should be done for both.
Thank you prof
In this indexed case of a DBD donor with
HBsAg negative
HBcAb positive
HBsAb negative
negative serology of HCV, and HIV screen, which indicates previous exposure with no immunity or controlled infection; resolving acute infection (window
period); or the possibility of occult HBV infection and there is a concern of reactivation after immunosuppression we need more history about the medical and social background of the donor including previous exposure, IV drug abuse, risky behavior, endemic area, infection screen in DD limited by the window period of infection
Anti-HBc of the IgM class indicates a current or recent infection with HBV, whereas anti-HBc of the IgG class indicates a past infection. The presence of hepatitis B surface antibody (HBsAb) in the blood is indicative of an immunologic response to HBsAg, and the higher the HBsAb titer, the lower the infectious risk associated with anti–HBc-positive donors which are not available in this case.
Will you accept this DBD donor?
YES organs from these donors may be transplanted in certain cases with appropriate HBV prophylaxis similar to the indexed case
So the answer will be Yes after screening for silent HBV infection in the donor by NAT for HBV DNA. Check the recipient’s vaccination status and the HBs AB titer . one prospective study found that kidney transplantation using organs from anti-HBc IgG-positive donors (even when they are concurrently anti-HBs negative) in anti-HBs-positive recipients is a safe procedure and may be considered as a way to expand the donor pool (1).
Occult or silent HBV infection OBI refers to the status of negative hepatitis B surface antigen and positive/negative anti-hepatitis B core immunoglobulin G status but hepatitis B virus (HBV) DNA is detectable in serum and liver tissue. Genotypes A, C, G, E, and D have been found among patients with OBI in different regions of the world.
Two types identified of silent HBV infection
1. Seropositive OBI, when the serum HBV DNA is detectable and both anti-HBc/anti-hepatitis B surface (HBs) IgGs are positive or only anti-HBc IgG is positive
2. Seronegative OBI. Only HBV DNA is detectable in serum/or liver tissue, but anti-HBc IgG/anti-HBs IgGs are negative in serum, it has been reported in up to 20% of cases of OBI. Patients at risk of OBI includes blood donors, health workers, hemodialysis patient, donors and recipients of SOT on immunosuppression, lymphoma, or other hematological malignancy on chemotherapy, co-infection with HIV, HCV with the impaired immune response they are at risk of reactivation of OBI with a previous history of HBV infection along with immunosuppression or chemotherapy status so to prevent such a risk the screening of HBV DNA should be implemented in blood donors, immunosuppressive patients, organ transplant donors, organ transplant recipients, and individuals with acute rheumatoid arthritis before and after treatment with anti-tumor necrosis factor (TNF)-α(2).
Will you accept this donor as a live donor if the recipient is also HB c Ab positive? If yes, what are the conditions that should be met?
This profile must be further investigated to clarify HBV status In patients with risk factors in the past for HBV infection: past, controlled infection; resolving acute infection (window period); or occult chronic infection. In patients with a recent history of blood/blood product transfusion: possible passively acquired anti-HB core antibody.
Donation is permitted if Anti-HBsAb titer >100 IU/L: with negative HBV-NAT, Between patients with past HBV (HBsAg negative, HBcAb positive), reactivation is more likely to occur in those with low or undetectable HBsAb levels and may be preceded by a fall in HBsAb levels over time.
it is recommended that HBV DNA is carried out in both donors and organ transplant recipients by highly sensitive molecular means. OBI reactivation may take place with increasing HBV DNA replication in patients during immunosuppression therapy. The risk of HBV reactivation is considered as high as 21% to 67%, especially with anti-CD20 rituximab and alemtuzumab with a mortality rate reported up to 20%.
References
1. Abrão JM, Carvalho MF, Garcia PD, Contti MM, Andrade LG. Safety of kidney transplantation using anti-HBc-positive donors. Transplant Proc. 2014 Dec;46(10):3408-11.
2.Makvandi M. Update on occult hepatitis B virus infection. World J Gastroenterol. 2016 Oct 21;22(39):8720-8734. doi: 10.3748/wjg.v22.i39.8720. PMID: 27818588; PMCID: PMC5075547.
3.González R, Torres P, Castro E, Barbolla L, Candotti D, Koppelman M, Zaaijer HL, Lelie N, Allain JP, Echevarría JM. Efficacy of hepatitis B virus (HBV) DNA screening and characterization of acute and occult HBV infections among blood donors from Madrid, Spain. Transfusion. 2010;50:221–230.
4. Sowole L, Labbett W, Patel M, O’Riordan A, Cross J, Davenport A, Haque T. The prevalence of occult hepatitis B virus (HBV) infection in a large multi-ethnic hemodialysis cohort. BMC Nephrol. 2015;16:12.
5. White SL, Rawlinson W, Boan P, Sheppeard V, Wong G, Waller K, Opdam H, Kaldor J, Fink M, Verran D, Webster A, Wyburn K, Grayson L, Glanville A, Cross N, Irish A, Coates T, Griffin A, Snell G, Alexander SI, Campbell S, Chadban S, Macdonald P, Manley P, Mehakovic E, Ramachandran V, Mitchell A, Ison M. Infectious Disease Transmission in Solid Organ Transplantation: Donor Evaluation, Recipient Risk, and Outcomes of Transmission. Transplant Direct. 2018 Dec 20;5(1):e416.
Thankyou Saja for confirming the fact as to rule out OCULT HBV in this LD IN BOTH D,R by full screen and mainly HBV DNA
yes will accept
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
yes I will accept
· HEV RNA SHOULD BE DONE TO EXCLUDE OCCULT INFECTION
· vaccination should be considered to boost the protective titre of HBsAb and minimise the risk of reactivation.
· Discussion with a specialist in viral hepatitis.
Please clarify your answer:
Who is immune.
Who is a healthy carrier
Who has a past infection and is also immune
Who has occult infection
TRY again.
then I will give you the answer!
Will you accept this DBD donor?
=========================
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
Reference
British Transplantation Society Guidelines for Hepatitis B & Solid Organ Transplantation, March 2018
In LD in the given situation (D,R are HBc Ab +) to clarify the status of each
The index D will still need a HBV DNA to rule out OCCULT HBV.
As for the R he will need a full screen ,and also rule out occult HBV.
Will you accept this DBD donor?
o Yes, I will accept this deceased donor with only HBcAb positive as HBV seroconversion risk is low and no excess risk of graft failure or short-term morbidity
o Kidneys from HBcAb positive organ donor can be used for any recipient and the risk of de novo HBV infection is low (Guidelines for Hepatitis B & Solid Organ Transplantation. British Transplantation Society Guidelines, 2018
o One review of core antibody positive donation to a large number of renal transplant recipients found that 45/1385 (3.2%) developed new HBV serological markers, but HBsAg seroconversion was seen in only four (0.28%) patients
o With this isolated HBcAb positive donor, lamivudine prophylaxis may be given for six months after transplantation, although the risk of transmission is very low
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
o This case should be discussed with a specialist in viral hepatitis
o Ask for recent HBV exposure (HBC IgM )
o HBcAb positive but HBsAg negative potential recipient (past infection): do HBV DNA and HDV serology testing to exclude occult HBV or HDV infection
o In HBcAb positive patient (past resolved infection), if HBsAb are <100 IU/mL, give vaccination to boost the protective titre of HBsAb and minimise the risk of reactivation
o Reactivation in patients with past resolved HBV infection (i.e. HBsAg negative/HBcAb positive is around 6.5% (particularly amongst recipients without HBsAb at the time of renal transplantation)
o HBV DNA and HBsAg should be monitored every 3 months in the first year and thereafter every six months individuals receiving a graft from a HBcAb positive donor, regardless of treatment or prophylaxis regimen
Serological markers for HBV infection
HBsAg, anti-HBs, HBeAg, anti-HBe, and anti-HBc IgM and IgG
HBsAg:
o Appears in serum within 1 to 10 weeks after exposture
o Persistence more than 6 months implies chronic HBV infection
o Titers are higher in patients with HBeA gpositive chronic hepatitis B (CHB) than in HBeAg-negative CHB
Anti-HBs (neutralizing antibody):
o Confers long-term immunity
o Are unable to neutralize the circulating viruses in most cases (so regarded as carriers of HBV)
o It is the only serological marker for vaccination
o Simultaneous appearance of HBsAg and anti-HBs may occur in patients with HBsAg positive
HBeAg and anti-HBe:
o For Infectivity and viral replication (replaced by HBV DNA)
o Seroconversion is related to the remission of hepatic disease
o Active viral replication is sustained in some patients with HBe seroconversion due to mutations in the pre-core and core region that inhibit or decrease the production of HBeAg
HBc Ag:
o Intracellular in infected hepatocyte and is not identified in the serum
anti-HBc:
o During acute infection, anti-HBc IgM and IgG appears 1–2 weeks after the presence of HBsAg along with raised serum aminotransferase and symptoms
o Anti-HBc IgM wears off after 6 months of acute infection
o Anti-HBc IgG continues to detect in both patients with resolved HBV infection and CHB
o Some HBsAg-negative individuals are positive for anti-HBc IgG without anti-HBs (isolated anti-HBc positive)
o Isolated anti-HBc positive seen in 3 conditions:
1. seen as IgM class during the window period of acute phase
2. after acute infection ended, anti-HBs has decreased below the cutoff level of detection
3. after several years of chronic HBV infection, HBsAg has diminished to undetectable levels
o In isolated anti-HBc positive, anti-HBc IgM should be checked to assess the possibility of recent HBV exposure
o HBV DNA should be tested in chronic liver disease patients to find out occult HBV infection (existence of detectable HBV DNA without serum HBsAg)
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.
Exellent answer but in the index LD with all the -ve serology ,short of HBV DNA you still have to rule out occult HBV so as to be a safe donor.
Kidney of 59- year male, DBD, HBsAg , HBsAb were negative. HBcAb positive, HBeAg and HBeAb were negative, Both HCV and HIV were negative.
1. Will you accept this DBD donor?
This donor has past HBV infection
Yes will accept this DBD donor
· Check the donor PCR if feasible.
· The risk for HBV transmission to the recipient in renal transplantation, seems to be low, especially in successfully vaccinated (anti-HBs concentration of <10IU/Ml)
· If the recipient is HBsA g positive.
· Lamivudine prophylaxis may be given for six months after transplantation or an HB Ig single-shot prophylaxis may reduce the risk of HBV seroconversion or reactivation.
· HBcAb-positive transplant recipients should be followed for the development of HBV by checking serologies for seroconversion.
2. Will you accept this donor as a living donor if the recipient is also HBc Ab positive? If yes why?
Yes will accept
· Will check for immunity status of recipient, if anti-HBs concentration of <10IU/mL will give HBV vaccine.
· Prophylaxis for recipients of HBcAb-positive kidneys using lamivudine may give protection.
· If the level of anti-HBs concentration of >10 IU/mL no need for prophylaxis as this level is considered protective.
· Important is close follow up with serum ALT, HBV DNA, and seroconversion, for evidence do novo infection.
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
Thankyou ( needless to say that in this LD situation the R has to have a full virology screen including HBV DNA to decide the risk stratification.)
Will you accept this DBD donor?
This potential donor is positive for HBc-Ab, although, not determined which one of anti-HBc antibody is positive. The followings may further explain this case scenario(1):
· The potential donor may have an occult HBV infection: Occult HBV infection is defined by persistence of low level of intrahepatic HBV DNA without detectable HBsAg. It is a serological situation defined by the presence of isolated anti-HBc with the absence of HBsAg and anti- HBs antibody.
· The potential donor may be in the window period of acute phase: seen predominantly as IgM class.
· The potential donor may have an acute HBV infection that had ended: anti-HBs has decreased below the cutoff level of detection. Patient in the convalescence phase with the detectable HBc-Ab mostly to be of IgM type.
Overall, I will accept this potential donor and proceed forward in the transplant process.
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(2). I will consider antiviral therapy for the recipient.
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
The HBcAb positive organ donor can be used for any recipient, and the risk of de novo HBV infection is low. 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(2).
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): As long as HBcAb positive donor is used, lamivudine prophylaxis may be given for six months after transplantation, although the risk of transmission is very low.
References
1. 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.
2. Guidelines for Hepatitis E & Solid Organ Transplantation; first edition (BTS guidelines)
Exellent so in the second scenario liver functions and staging of disease is needed in this case ( even in non liver TX).
I would accept this DBD donor but need to manage the recipient for denovo HBV infection according to his/her HBV status.
we can stratify the recipient as
•High risk recipient- HbsAg-ve, Anti Hbc-ve, anti hbs-ve(susceptible)
•Moderate risk- HbsAg+ve, anti Hbc igg+ve, Anti hbs –ve (chronically infected) and
Hbsag-ve, Anti hbc+ve, Anti hbsAg-ve (prior infection)
Mild risk recipient- HbsAg-ve, Anti Hbc+ve, Anti Hbs+ve(immune due to natural infection)
and Hbsag-ve, Anti-Hbc-ve, Anti Hbs+ve (immune due to
vaccination)
Antiviral for prevention of denovo infection and re activation
Life long- antiviral for moderate risk
One year for high risk, mild risk
Antiviral to be started at the time of transplantation
and need to monitoring HBsAg, HBcAb every 3 month for 1 year, then every 6 months DNA (NAT)
Choice of antiviral
Entecavir or tenofovir alafenamide (if patient had received lamivudine in past, then preferred tenofovir alafenamide)
Yes will accept this donor as live donor only if HBcAb Igm of recipient is negative
If the recipieent is HbcAb positive he may be
Moderate risk recipient- HbsAg+ve, anti Hbc igg+ve, Anti hbs –ve (chronically infected)
and
Hbsag-ve, Anti hbc+ve, Anti hbsAg-ve (prior infection)
or
Mild risk recipient- HbsAg-ve, Anti Hbc+ve, Anti Hbs+ve(immune due to natural infection)
Need to see HBV DNA load and liver enzymes (withing normal limits)
Antiviral for prevention of denovo infection and re activation
Life long- antiviral for moderate risk
One year for high risk, mild risk
and need to monitor HBsAg, HBcAb every 3 month for 1 year, then every 6 months DNA (NAT)
Choice of antiviral
Entecavir or tenofovir alafenamide (if patient had received lamivudine in past then preferred tenofovir alafenamide)
Induction agents– consider basiliximab instead for lymphocyte depleted and steroid free manintanence immunosuppression. not to use rituximab
1)Lecture : May A Hassaballa HEV in kidney transplant
2)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.
Well done for selecting the induction agent.
Will you accept this DBD donor?
We accepted this patient who HBcAb positive with negative HBsAg .
The HBcAb positive (HBsAg negative) donor liver can be used for any potential liver recipient.
When the liver comes from a HBcAb positive donor and is given to a HBV immune or non-immune recipient, prophylactic lamivudine for 6 month should be given from the time of transplantation.
Donation of non-liver solid organs from the core antibody positive donor is rarely associated with de novo infection of the recipient.
Though serological signs of HBV infection may be documented (such as the development of HBcAb in a non-immune recipient), serum HBsAg seroconversion (de novo infection) is rarely observed with this postive HBcAb and negative to HBsAb,HBsAg ,HBeAb and HBAg may reflect prior infection and liable to reactivation there for HBVDNA testing is mandatory.
Monitor HBV DNA, and HDV serology, every 3 months in the 1st year and then every 6 months thereafter and accordingly.
According to the antibody titer recipient should receive HB vaccination.
One review of core antibody positive donation to a large number of renal transplant recipients found that 45/1385 (3.2%) developed new HBV serological markers, but HBsAg seroconversion was seen in only four (0.28%) patients [12].
With such a low risk for de novo infection, it is hard to demonstrate a benefit of antiviral prophylaxis.
Pre-transplant recipient HBV immunity appears to protect against de novo infection.
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes,
what are the conditions that should be met?
Yeas I will .
HBcAb may differentite as :
HBsAg+ve recipient.( Lamivudine administered for one year if donor HBV PCR is positive along with HBV immunoglobuline)
Hepatitis B immune recipient.( with anti-Hepatitis B s antibody titer of more than 10 IU/ml)
Hepatitis B non-immune recipient.( single dose of 2000 HBV immunoglobulin if HBV PCR was not done)
Reference
1.Mahboobi N, Tabatabaei SV, Blum HE, et al. Renal grafts from anti hepatitis B core positive donors. A quantitative review of the literature. Transpl Infect Dis 2013; 14: 445-51.
2.Pilmore HL, Gane EJ. Hepatitis B positive donors in renal transplantation: increasing the deceased donor pool. Transplantation 2012; 94: 205-10.
3.Rosemary Ouseph et al. Review of the use of hepatitis B core antibody–positive kidney donors.Transplantation ReviewsVolume 24, Issue
The DD ‘s liver can harbour in this case a state of occult HBV so a HBV DNA is a must if you decide to use this liver, or at least a prophylaxis should be strongly implemented .
Stored samples from a DD are very informative when needed.
Will you accept this DBD donor?
Yes, I would accept this donor’s organ.
Hepatitis B virus (HBV) infection is a major risk factor for liver injury after kidney transplantation.
As an Anti-HBc IgM and IgG rise in 1–2 weeks after the presence of HBsAg along with raised serum aminotransferase and symptoms during acute infection (window period). After 6 months of acute infection. anti-HBc IgM becomes negative, and Anti-HBc IgG positive in resolved HBV infection and Chronic HB.
Thus, donor medical chart, and detailed history might be informative to clarify the distinct of HBV status( either acquired by blood product transfusion, resolving acute infection, or occult chronic infection), so HBV PCR should also be taken from the donor- UK guidelines stated that: All donors who are positive for HBcAb but HBsAg negative (past HBV exposure) must have HBV DNA testing to exclude the possibility of occult HBV infection. (1C)
Amongst patients with past HBV (HBsAg negative, HBcAb positive), reactivation is more likely to occur in those with low or undetectable HBsAb levels and may be preceded by a fall in HBsAb levels over time.
I would check the recipient vaccination chart for hepatitis B if HBs Ab titer > 10 means that he is immunized, so I would do transplant such a patient.
But I would explain the risk of having active disease, with fulminant hepatitis, and death.
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
Yes, I will accept this living donor with anti HBc Ab
But before I would ask for HBs Ab, HBs Ag, and HBe Ab.
Anti-HBc antibody positive (HBsAg negative) patients should not be excluded from kidney transplantation (1C).
Anti-HBc antibody positive (HBsAg negative) patients should not receive antiviral prophylaxis given that the risk of reactivation is low (1D).
Anti-HBc antibody positive (HBsAg negative) patients have a plan in place for post-transplant monitoring of HBsAg and HBV DNA for a minimum of 1-year post-transplantation.(1C)
If the donor has a chronic infection of Hepatis B – in spite of low risk of viral infection the recipient should receive anti- viral prophylaxis for up to one year with lamuvidin most widely used.
Ensure that the recipient is immunized – received HB vaccine with anti HBs AB >10 , this strategy found to be protective.
References:
(1) Abrão JM, Carvalho MF, Garcia PD, Contti MM, Andrade LG. Safety of kidney transplantation using anti-HBc-positive donors. Transplant Proc. 2014 Dec;46(10):3408-11. doi: 10.1016/j.transproceed.2014.06.067. PMID: 25498061.
(2) Chadban, Steven J. BMed, PhD1,*; Ahn, Curie MD, PhD2; Axelrod, David A. MD, MBA3; Foster, Bethany J. MD, MSCE4; Kasiske, Bertram L. MD5; Kher, Vijah MD, DM6; Kumar, Deepali MD, MSc7; Oberbauer, Rainer MD, PhD8; Pascual, Julio MD, PhD9; Pilmore, Helen L. MD10; Rodrigue, James R. PhD11; Segev, Dorry L. MD, PhD12; Sheerin, Neil S. BSc, PhD13; Tinckam, Kathryn J. MD, MMSc7; Wong, Germaine MD, PhD14; Knoll, Gregory A. MD, MSc15,*. KDIGO Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation. Transplantation 104(4S1):p S11-S103, April 2020.
(3) 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.
Well done.Very comprehensive plan.
Thank you Prof. Dawlat
The index patient is being offered a DBD (donor after brain death) donor with good terminal renal function. The donor is HBcAb positive. Other serological tests (HBsAag, HBeAg, HBeAb, HIV and HCV) are negative.
Positive Anti-HBcAb signifies either a resolving acute infection (Anti HBcAb IgM positive), or a resolved HBV infection (Anti HBcAb IgG positive), or a low level chronic infection (HBV DNA PCR positive).
As per the British Transplantation Society guidelines, kidneys from HBcAb positive donors can be used for any recipient, the risk of de novo HBV infection being low (1).
Hence, I will accept this DBD donor.
Lamivudine prophylaxis for 6 months post-transplant can be given to the recipient if the recipient is non-HBV immune (1,2).
If the recipient is anti-HBs positive (HBV immune), then there is no need of antiviral prophylaxis (3).
Yes. A HBcAb positive live donor can be accepted for HBcAb positive recipient (1).
Donor: In case a live donor, if during pre-donation evaluation, is found to be HBcAb positive and HBsAg negative, then HBV DNA testing of the donor should be done (to rule out occult HBV infection). The prospective donor should be evaluated thoroughly including liver function tests and abdominal ultrasound. The type of HBcAb (IgG or IgM) should be tested.
Recipient: If the recipient is also HBcAb positive, other markers like HBsAg, HBsAb, HBeAg, HBeAb, and HBV DNA PCR and HDV serology (to rule our HDV co-infection) should be done.
If HBcAb positive and Anti-HBsAb <100 IU.ml, vaccination should be considered for the recipient to boost HBsAb titres.
It has been recommended that routine antiviral prophylaxis (tenofovir or entecavir) are not required in those with markers of past HBV infection (HBsAg negative, HBcAb positive, with or without Anti-HBsAb), but they may be given if the recipient is Anti-HBcAb positive alone, or has detectable HBV DNA, or requiring intense immunosuppression like rituximab, ATG use (3).
So, in this scenario, if only HBcAb is positive in recipient, antiviral prophylaxis would be required.
Patient should be monitored with liver enzyme, HBsAg and HBV DNA once in 3 months for at least 1 year post-transplant, and during periods of intense immunosuppression, if prophylaxis is not given and antivirals can be initiated if HBsAg becomes positive or HBV DNA titres rise (1,3).
In nutshell, this clinical scenario requires:
1) Recipient should be counselled regarding the clinical scenario.
2) Hepatologist should be involved in management.
3) Donor HBV DNA should be checked.
4) Recipient should be vaccinated.
5) Post-transplant antiviral prophylaxis would be required.
6) Regular post-transplant monitoring of LFT, HBsAg and HBV DNA should be done as per protocol.
References:
Thankyou well done ,the -ve HBeAg, and HBeAb means he has no virus replication(no or low INFECTIVITY) so your vaccination/prophylaxis plan is correct.
In the second part of the scenario you well confirmed a full virology screen for the R with HBV DNA and a well planed vaccination/prophylaxis.
well done very well structured (not just copy ,paste guidelines.
Will you accept this DBD donor?
Yes, with the current marked imbalance between the supply and demand for organs, this donor can be accepted.
BTS clearly stated that non-liver solid organs from the HBcAb positive organ donor can be used for any recipient, and the risk of de novo HBV infection is low.
Isolated HBcAb can be seen in the following condition:
– Window period of acute phase; predominantly IgM class.
-After acute infection had ended, anti-HBs has decreased below the cutoff level of detection.
-After several years of chronic HBV infection, HBsAg has diminished to undetectable levels.
In this case we should check the possibility of:
– Recent HBV exposure by anti-HBc IgM.
– Occult HBV infection(existence of detectable HBV DNA without serum HBsAg) by checking Real time PCR (HBV DNA assays)
– Despite the low risk of transmission is very low, lamivudine prophylaxis may be given for 6 months after transplantation, when a HBcAb positive donor is used.
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
Yes, this donor can be accepted and we need to rule out the possibility of :
– Recent HBV exposure.
– Occult HBV infection.
Occult HBV infection is defined by:
– Persistence of low level of HBV DNA without detectable HBsAg
– Presence of isolated anti-HBc with the absence of HBsAg and anti- HBs antibody
-The detection of HBV DNA in the liver is the gold standard of diagnosis for occult HBV, invasive and not performed usually.
The clinical importance of Occult HBV infection: .
– Transmission via transfusion, SOT or hemodialysis
– Risk of reactivation of HBV in immunocompromised state.
– It may accelerate liver injury and lead to hepatic fibrosis
– it is a risk factor for HCC.
In this setting check the donor for:
– LFT enzymes.
– HBV DNA ( PCR)
– Repeat serology; HBcAg IM and IgG
– Check for co-infection with HDV.
– Liver US
For the recipient:
– Check HBV status; serology HBsAg, HBsAb, HBcAb IgG& IgM, HBV PCR, HDV. Other viruses as per guidelines.
– Lamivudine prophylaxis may be given for 6 months Post-KT t, although the risk of transmission is very low although monitoring for HBV recurrence is an equally acceptable strategy.
– Monitoring for HBV Recurrence or De Novo Infection; HBV DNA and HBsAg should be monitored every 3 months in the first year and then every 6 months in HBsAg positive liver transplant recipients or
individuals receiving a graft from a HBcAb positive donor, regardless of treatment or prophylaxis regimen.
– Recipient will ideally have been effectively immunized against HBV.
– KTR with HBcAb positive, if HBsAb are <100 IU/mL, should be vaccinated to decrease transmission risk
– High-dose, accelerated vaccine schedule, second series can be given if no response.
– KTR who have a resolved infection of HBV (defined by positive anti-HBc serology) should be aware of a possibility of HBV reactivation during a course of intensive IS particularly Rituximab ( regardless donor status)
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.
Exellent ,well done
This LD in the index case is well worked out .
The R as you mentioned has to be fully screened before accepting.
Donor acceptance
I would accept this donor because he is HbsAg negative, anti HBc positive, both HBeAg and HBeAb negative. This donor is non-infectious to others.
However, there is risk of de novo HBV in recipient with this donor.
Since donor is HBcAb positive, recipient can be given lamivudine prophylaxis for 6 months post transplant.
If recipient has history of HBV infection previously with reports of HBcAb positivity, then the recipient could be at risk of this infection reactivating post transplant. Thus, I would consider 6 months prophylaxis of antiviral therapy. Careful monitoring for HBV recurrence is also necessary in this recipient.
If recipient is HBV naive, then vaccination has to be done.
Live donor with HBcAb positive recipient
Since recipient is HBcAb positive, if titles are below 100 IU/ml then he/she should be vaccinated in order to reduce incidence of reactivation. If the patient fails to respond, then second series can be considered.
Since donor is live, test for HIV, HEV and HCV active infection.
Do HBV DNA for the donor to check for occult infection.
If donor has no active viral infection, has HBV DNA undetected, then I would accept this live donor.
Do HBV serology every 3 months in the first year post transplant, followed by twice a year from second year onwards.
References :
1.Prof May Hassaballa. Kidney Tx in patients with HBV, HEV. Cairo University. World kidney Academy. 2023.
2.BTS. Guidelines for Hepatitis B & Solid organ transplantation. 2023.
Agree if the living donor is -ve for HBe Ag ,HBe Ab therefore he has no virus REPLICATION.
However you still need HBV DNA ,if that is -ve then the R can be vaccinated and LAMIVUDINE prophylaxis.
Interpretation of results for isolated anti-HBc. There are different possibilities which includes the following:
In order to determine the source and significance of the anti-HBc positivity, a repeat testing for anti-HBc, HBsAg, anti-HBs and anti-HBe is checked.
HBV DNA level should also be checked in isolated anti-HBc antibody.
Will you accept this DBD donor? Yes. However, if the recipient has no previous infection or vaccinated, transplantation the donor will not be accepted except in extreme cases. The recipient will also need to be on prophylaxis with either entecavir or tenofovir.
Rationale is that this could be a potential case of either an acute or even a chronic infection as highlighted earlier and may constitute a high risk for the recipient especially if recipient is immune naive.
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
Yes, and the conditions will include:
Reference
I like your analysis. However, you mention as I quote you, “donor will be on treatment to suppress HBV DNA to undetectable level before donation except in extreme cases.”
My question to you:
Do you really have enough time to treat DBD donor with anti-viral ?
No sir. I was responding to the second aspect of the question for live donation.
If the donor is a live :
HBcAb-ve/ HBsAb-ve =low risk
HBsAg-ve/ HBsAb-ve =low to moderate risk.
HBcAb+ve/ HbsAb-ve =moderate to high risk.
HBsAg+ve/ HbcAb+ve = very high risk
Reference:
BTS guidelines for Hepatitis B & Solid Organ Transplantation, 18th edition,2018.
Not HBV RNA, I mean DNA
Yes, I like that self-correction
· Will you accept this DBD donor?
Yes as the donor has no active infection but immune by natural old infection the risk of getting HBV infection is low
But the following is required
Evaluation of HBV DNA and HDV RNS for any dormant infection
Lamivudine prophylaxis is recommended life long
Testing every 3 months for HBV and HDV serology for the 1st year then every 6 months after 1styear
Will you accept this donor as a liver donor if the recipient is also HBcAb +ve?
Yes of course with the same protocol mentioned above
Ref
https://bts.org.uk/wp-content/uploads/2018/03/BTS_HepB_Guidelines_FINAL_09.03.18.pdf
-Will you accept this DBD donor?
Yes can be accepted according to the recipient virological status and immunity certain considerations .
HBcAb positive donors can be donated to any recipient, as de novo HBV infection is low meanwhile lamivudine prophylaxis may be given for 6 months after transplantation.
This donor is HBc Ab positive while HBsAb ,HbsAg ,HBe Ag and HBe Ab are negative means that he had prior HBV infection and is liable to reactivation
HBV DNA testing is needed
So the risk of HBV infection transmission to the recipient from this Hbc Ab positive donor will vary according to virological recipient’s status so
· If the recipient had HBs Ag,HBs Ab, HBc Ab negative ,he will be highly susceptible to develop HBV infection
· If the recipient had HBs Ag, negative and HBs Ab, HBc Ab are positive then he will be immune due to natural infection and the risk will be low
· If the recipient had HBs Ag, HBc Ab negative HBs Ab is positive denoting vaccination and immunity also the risk will be low
· If the recipient had HBs Ag, HBc Ab, HBc Ab Ig M positive , HBs Ab is negative indicating acute infection so it suitable to receive this donor’s graft
· If the recipient had HBs Ag, HBc Ab, positive and HBs Ab, HBc Ab Ig M are negative indicating chronic infection so the risk will be moderate
· If the recipient had HBc Abpositive and HBs Ag, HBs Ab are negative the same as the donor virological status indicating also previous HBV infection ,therefore the risk will be moderate
In this case the recipient has to receive antiviral therapy at the time of transplantation and to monitor carefully the immunosuppression and titrate the dose as needed to maintain immunity against the HBV infection and at the same time guard against rejection risk .
Tenofovir with lower renal toxicity or entecavir according to creat. clearance dose adjustment can be given , it is preferred than Lamivudine for the sake of safety profile with long duration therapies
HBV DNA and HBsAg need monitoring every 3 months in the first year and then every 6 months
In fact Risk benefit has to be weighed with counselling of the recipient considering the age of the recipient, his medical condition and co morbidities ,matching and desensitisation need, time spent on waiting list
-Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
Yes ,Antiviral therapy can be given for lifelong in this case with prior HBV infection with monitoring /3 months for 1 years testing HB sAg HBcAb then every 6 months by testing HBV DNA
Reference
– Guidelines forHepatitis B & Solid Organ Transplantation, BTS March 2018
– Chan T M etal .Kidney transplantation in adults: Hepatitis B virus infection in kidney transplant recipients.Uptodate2022
Will you accept this DBD donor?
Yes, because the risk of de novo HBV infection is very low.
Will you accept this donor as a liver donor if the recipient is also HBcAb +ve?
Yes, I will accept
Reference
BTS guidelines 2018.
You were offered kidneys from a 59-year-old male DBD (donor after brain stem death) donor who suffered from SAH (grade 5) complicating cerebral aneurysm. His retrieval S Cr was 72 µmol/L. Virology was reported as follows: HBsAg negative, HBsAb negative, HBcAb positive, and both HBeAg and HBeAb are negative. Both HCV and HIV are negative.
NDD Virology Status:
HBsAg negative, HBsAb negative, HBcAb positive,
HBeAg and HBeAb are negative,
HCV and HIV Ab are negative.
DD:
New infection or recovering from acute HBV infection.
Chronic infection with low antibodies.
False-positive anti-HBc.
Will you accept this DBD donor?
YES, IF;
After HBV DNA status If donor is negative on HBV PCR testing.
If Recipient is immunized with anti-Hepatitis B s antibody titer of more than 10 IU/ml and
preferably more than 100 IU/ml after boosting the recipient with anti HBV vaccine
If HBs Ab is more than 100 an HBV DNA in not detected, the infectious risk is low.
There are several reports of kidney transplanted from HBsAg/DNA negative.
the prospective recipient will effectively be immunized against HBV.
single dose of 2000 HBV immunoglobulin if HBV PCR was not done.
The addition of antiviral drug may be considered especially in low HBs Ab response to
vaccination=> Lamivudine or Entecavir administered for one year if donor HBV PCR is positive along with HBV immunoglobulin.
Most transplant units will not accept potential donor with active viral replication.
References;
*British Transplantation Society Guidelines: March 2018.
*UpToDate
*Hyejin Mo et al. Outcome after kidney transplantation in hepatitis B surface antigen-positive patients. Scientific Reports volume 11, Article number: 11744 (2021)
Virology was reported as follows: HBsAg negative, HBsAb negative, HBcAb positive, and both HBeAg and HBeAb are negative. Both HCV and HIV are negative.
The possibilities of this results are :
1-New infection .
2-chronic infection with low antibodies .
yes ,but I would like to do HBV DNA
if HBSAb is more than 100 an HBV DNA in not detected ,the infectious risk is low .
There are a number of reports of kidney transplanted from HBsAG/DNA negative
the prospective recipient will effectively immunized against HBV .
The addition of antiviral drug maybe considered especially in low HBs AB response to vaccination .
MOst transplant units will not accept potential donor with active viral replication .
reference :
BTS guideline .
I appreciate your step-wise clinical approach in managing this patient
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 isolated anti-HBc positivity (negative for both HBsAg and anti-HBs)
Donor evaluation
Approach for transplanting kidney from anti-HBc positive donor to naive transplant recipient (Will you accept this DBD donor?)
A- Evaluation of the donor risk
B- Selecting the appropriate recipient
C- Use of antiviral prophylactic therapy
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 previous infection (HBsAg negative, anti-HBc positive) (Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?)
To conclude
I will do PCR for the donor and antiHBs Ab for the recipient to evaluate the risk, I will accept this DBD donor with isolated anti-HBc positive to naive transplant recipients under the following circumstances
On the other hand, I will you accept this donor as a live donor if the recipient is also HBcAb positive since transplant recipients with prior infection can receive kidney from any donor regardless of HBV status under cover of life long or 1 year antiviral therapy with close monitoring
References
1- Chen GD, Gu JL, Qiu J, Chen LZ. Outcomes and risk factors for hepatitis B virus (HBV) reactivation after kidney transplantation in occult HBV carriers. Transpl Infect Dis 2013; 15:300.
2- Abrão JM, Carvalho MF, Garcia PD, et al. Safety of kidney transplantation using anti-HBc-positive donors. Transplant Proc 2014; 46:3408.
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- Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology 2018; 67:1560.
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 make note of your interpretation of serological and molecular testing reports pertaining to HBV infections in relation to timings in the natural history HBV infections. I like your summary.
Will you accept this DBD donor?
YES
HIGH RISK DONOR
Four interpretations:
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
YES ACCEPT
Recipients who are anti-HBc positive have evidence of prior infection, and HBV reactivation may occur secondary to immunosuppressive therapy. The presence of anti-HBs at time of transplantation may not prevent reactivation, because anti-HBs titer can decrease and become undetectable with immunosuppression.
The duration of antiviral therapy can vary. Some centers administer antiviral therapy indefinitely to all recipients with prior HBV. Others discontinue treatment when immunosuppression is reduced to low-dose maintenance level and monitor closely thereafter, unless the patient is receiving immunosuppression with an agent associated with a high risk of HBV reactivation (eg, rituximab).
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 chronic kidney disease and immunosuppressive medications.
If antiviral therapy is administered, the optimal duration is unknown; Aadminister therapy for 1 year.According HBV viral load
I appreciate your clinical approach.
Typing whole sentence in bold amounts to shouting.
Thanks .Prof. Ajay Sharma
Noted
I will accept the donor,
Owing to the fact that HB c antibody positive donor might indicate a previous infection in the donor, even with HB s Ag negative status. risk of recipient seroconversion is 4 % if virology status showed Anti HB s Ab positive of a titer exceeding 10 iu/ml and risk of around 10% with lesser titer. nevertheless, risk of transmission is dependent on virology load, If PCR for HBV is positive then increasing risk of transmission necessitated the administration of HBV immunoglobulins and Lamivudine prophylactic therapy along with immunization of recipient. If he is non immunized. however, is PCR is negative then risk of transmission is negligible.
If the donor and recipient both are Hepatitis B core antibody positive , I will accept the donation if:
1] The donor is negative on HBV PCR testing.
2] Recipient is immunized with anti-Hepatitis B s antibody titer of more than 10 IU/ml and preferably more than 100 IU/ml after boosting the recipient with anti HBV vaccine.
3] single dose of 2000 HBV immunoglobulin if HBV PCR was not done .
4] Lamivudine administered for one year if donor HBV PCR is positive along with HBV immunoglobuline.
References:
1]Rosemary Ouseph et al. Review of the use of hepatitis B core antibody–positive kidney donors.Transplantation ReviewsVolume 24, Issue 4, October 2010, Pages 167-171.
2] Hyejin Mo et al. Outcome after kidney transplantation in hepatitis B surface antigen-positive patients. Scientific Reports volume 11, Article number: 11744 (2021)
I appreciate your clinical approach.
Short and sweet.
I appreciate your clinical approach.
Short and sweet.
Will you accept this DBD donor?
The donor is only hepatitis B core Abs +ve
Interpretation unclear; four possibilities:
1. Resolved infection (most common)
2. False-positive anti-HBc, thus susceptible
3. “Low level” chronic infection
4. Resolving acute infection
Isolated positive hepatitis Bc Abs seems to be dismal for recipients of renal transplantation with potential risk of HBV during immunosuppression. Due to the risk of reactivation, prophylactic lamivudine or entecavir should be considered with regular testing of HBV DNA and HBsAg
In the era of kidney donors shortage, I will accept this donation.
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
considering the recipient has received a full vaccination for HBV, or if the patient is HBs Ag +ve with HBs Ab titer > 10 IU/L, or if the recipient is a very low risk of transmission in HBs Ab -ve recipient.
I appreciate your clinical approach.
Short and sweet.
Will you accept this DBD donor?
Isolated positive anti-HBc antibodies can be explained by a variety of clinical conditions, such as acute hepatitis B, cured HBV infection, declining anti-HBs titer, and false positives.
The effect of donors with positive HBc antibodies in renal transplantation seems to be minimal. According to donor and recipient immunological state, there is a moderate risk of HBV reactivation in kidney transplants, without antiviral treatment. Pre-transplant recipient HBV immunity appears to protect against de novo infection following donation of solid organs other than the liver from a core antibody positive donor.
In the first year following a kidney transplant, HBV DNA and HBsAg should be checked every three months, and then every six months. Patients with occult HBV infection should be treated similarly to those who test positive for HBsAg. One to five percent of kidney transplant recipients are thought to be at risk of HBV reactivation. Hence, prophylaxis is recommended to reduce the risk of infection reactivation. Consider prophylaxis with antiviral therapy for up to a year while also monitoring out for HBV recurrence in this donor with HBcAb positive serology. In this patient, antiviral prophylaxis with lamivudine or entecavir are indicated.
So Yes, I will accept this donor.
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
Yes, I will accept the offer from an HBcAb-positive living organ donor as long as the recipient has received a successful vaccination, has an HBsAg-positive HBs Ab titer of >10 IU/L, or has a very low risk of transmission if the recipient has HBsAb-negative recipients.
I appreciate your careful well balanced clinical approach in managing this patient that is well supported by evidence.
Typing whole sentence in bold amounts to shouting.
Will you accept this DBD donor?
In the current index case, the potential deceased donor virology screen revealed:
HBsAg negative, HBsAb negative,both HBeAg and HBeAb are negative and isolated HBcAb positive. Both HCV and HIV are negative.
Basically, Hepatitis B core antibody (HBcAb) is the first antibody to appear following acute hepatitis B infection and will persist in high levels following resolution of infection and in chronically infected patients. Resolved infection is recognized by the presence of (HBsAb) in the serum.In chronic infection (HBsAg) is typically present.
Isolated HBcAb, which is defined as positive HBcAb with undetectable HBsAg and HBsAb can occurs in one of several clinical situations:
-The only marker for Acute hepatitis B infection during “window phase”.
-It can be presents between disappearance of HBsAg and appearance of HBsAb. -It can represent remote resolved infection with the decline of HBsAb to undetectable levels.
-Ongoing chronic infection with HBsAg that is undetectable, either because of low levels of HBsAg or because of mutations.
*In the current scenario, it represents prior hepatitis B infection with negative HBS Ag and HBS Abs.
The answer to the question: Yes will accept the offer. The risk of developing a de novo HBV infection after transplantation from HBcAb-positive donors may be up to 70% in liver transplant recipients, while the negative impact of HBcAb-positive donors in renal transplantation appears low to negligible.
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
Yes ,I will accept the offer from HBcAb-positive living organ donor provided that successfully vaccinated recipient or in recipients with HBsAg-positive with HBs Ab titer >10 IU/L as well as for recipients with HBsAb-negative recipients with a very low risk of transmission.
In these patients,antiviral prophylaxis with lamivudine or, alternatively, with entecavir are indicated.
Referrences:
Fong TL, Bunnapradist S, Jordan SC, Cho YW. Impact of hepatitis B core antibody status on outcomes of cadaveric renal transplantation: analysis of United Network of Organ Sharing Database between 1994 and 1999. Transplantation. 2002;73:85–89.
Veroux M, Puliatti C, Gagliano M, et al. Use of hepatitis B core antibody-positive donor kidneys in hepatitis B surface antibody-positive and -negative recipients. Transplant Proc. 2005;37:2574–75.
I appreciate your careful well balanced clinical approach in managing this patient that is well supported by evidence.
Typing whole sentence in bold amounts to shouting.
Patient with folloing result HBsAg negative, HBsAb negative, HBcAb positive, HBeAg and HBeAb are negative. HCV and HIV are negative.Will you accept this DBD donor;Yes i will accept his kidney
HBV DNA testing is utilized to identify occult HBV infection since a deceased donor has isolated anti-HBc in the absence of HBsAg and anti-HBs antibody.
It shows that there is very little chance of HBV transmission from kidney donors who have tested positive for HBcAb.
As a result, ESRD patients can receive kidney transplants from these donors without risk.
If it is a living donor and the recipient is also HBcAb positive;
Yes I will accept if the below criteria are full filled
HBV DNA viral load that has not been found in the recipient or donor to rule out occult infection
To rule out the potential of an active, ongoing infection, test for anti-HBc IgM and IgG.
Normal liver synthethetic profile including ALT, may require liver biopsy to rule out fibrosis or fibroscan.
Informed consent explaining risk of de novo and reactivation of disease and prognosis
Level of HBsAb and vaccination accordingly.
Renal grafts from anti-hepatitis B core-positive donors: a quantitative review of the literature Mahboobi N, Tabatabaei SV, Blum HE, Alavian SM. Renal grafts from anti-hepatitis B core-positive donors: a quantitative review of the literature. Transplant Infectious Disease 2012; 14(5): 445-451
Guidelines for Hepatitis B and Solid Organ Transplantation.BTS. First Edition 2018
Transplanting kidneys from donors with prior hepatitis B infection: one response to the organ shortage
Fabrizio Fabrizio 1 , Suphamai Bunnapradist, Paul Martin
I appreciate your careful well balanced clinical approach in managing this patient that is well supported by evidence.
Typing whole sentence in bold amounts to shouting.
HBsAg negative, HBsAb negative, HBcAb positive, and both HBeAg and HBeAb are negative. Both HCV and HIV are negative.
Will you accept this DBD donor?
Yes, I will accept .
Our deceased donor has isolated anti-HBc with the absence of HBsAg and anti- HBs antibody, thus HBV DNA testing used to diagnose occult HBV infection, and non-liver organ transplantation such as 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 (1).
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
Yes, I will.
If recipient is HBc Ab positive and HBs Ab negative or titer less than 10è will consider vaccination, prophylaxis with high dose Immunoglobulin or Lamivudine and strict follow up by HBV PCR and liver function test.
If HBs Ab titer >10 iu/L , no need for prophylaxis and clinical follow up with HBV PCR and liver function.
References:
1-Mahboobi N, Tabatabaei SV, Blum HE, et al. Renal grafts from anti hepatitis B core positive donors. A quantitative review of the literature. Transpl Infect Dis 2013; 14: 445-51.
2– British Transplantation Society Guidelines: Guidelines for Hepatitis B & Solid Organ Transplantation 2018.
3-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 step-wise clinical approach in managing this patient that is well supported by evidence.
Will you accept this DBD as a donor?
Yes, I will accept the donor because of the following reason
In the above situation, the use of lamivudine for 6 months has been suggested by the BTS guidelines
Will you accept the same organ if it is a living donor and the recipient is also HBcAb positive
Yes, I will accept after the following condition is met
The persistently low-level HBV DNA in the absence of anti-HBs is a pointer to occult HBV infection.
Post kidney transplantation
References
Well done.Prophylactic use of Antiviral course is mandatory in a HBVc recipient could be an occult HBV and should not be neglected.
Noted Prof
Thank you.
3. You were offered kidneys from a 59-year-old male DBD (donor after brain stem death) donor who suffered from SAH (grade 5) complicating cerebral aneurysm. His retrieval S Cr was 72 µmol/L. Virology was reported as follows: HBsAg negative, HBsAb negative, HBcAb positive, and both HBeAg and HBeAb are negative. Both HCV and HIV are negative.
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History
Will you accept this DBD donor?
Yes I will accept this donor because ;-
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Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
YES I will accept this donor post evulation
Risk of HBV infection/ reactivation in non-liver SOT without antiviral prophylaxis/treatment(Moderate – high)
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Thankyou well done for dealing with the living donation scenario differently.If RECIPIENT is HBVc positive, could be OCCULT state and should treated as HBsAg +.
Many tahanks Prof.Dalwat
Yes Prof.
Four interpretations of the HBV panel
After counseling the recipient, I will ask the hepatologist to start entecavir directly post-transplant.
References:
-Centers for Disease Control and Prevention, Hepatitis B information for health professionals: Interpretation of hepatitis B serologic test results. Available from the CDC website
Guidelines for Hepatitis B & Solid Organ Transplantation (BTS)
Well done.
1.Will you accept this DBD donor?
2.Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
Reference:
BTS guideline 2017
Can you please elaborate on the choice of the recipients!
This type of donor (HBcAb positive & HBsAg negative) can be use for any liver recipient ideally in the following order: first option for HBsAg positive recipient, second option for HBV-immune recipient and lastly for HBV non-immune recipient
The use of anti-HBc antibody-positive kidneys is considered a safe way to expand the donor pool as it is associated with negligible risk of transmission of HBV infection, depending on the recipient’s protective immunity status .
Causes of isolated HBcAb :
– Early window period of acute hepatitis B.
– Resolved HBV infection with warning of anti-HBs titer.
– A false positive anti-HBc.
– An occult chronic HBV infection with low viremia and undetectable HBsAg.
Kidney transplantation from anti-HBc positive donors can be performed safely without the need for prophylaxis in recipients with HBV immunity (>10 IU/mL). In patients with low titer of anti-HBs (<10 IU/mL), a pre-transplant vaccine booster should be administered and, if successful, no prophylaxis is needed. In patients not responding to vaccines, consider prophylaxis with hepatitis B Immunoglobulin or lamivudine.
– Yes, I will accept this donor .
Any potential transplant recipients found to be HBcAb positive but HBsAg negative (past infection) must have HBV DNA and HDV serology testing to exclude occult HBV or HDV infection. If proved no occult chronic infection and the kidney recipient is immune (anti HBs > 10 mIU/mL) , 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. if the positive recipient has low immunity (anti-HBs <10 IU/mL) prophylaxis with hepatitis B Immunoglobulin or lamivudine may be needed after a booster dose of hepatitis B Vaccine .
Reference :
1. UC Davis Health Transplant Center Non Living Donors Hepatitis B Core Antibody Positive Donors
2. Med Sci Monit. 2016; 22: 1427–1434. Published online 2016 Apr 28. doi: 10.12659/MSM.896048
3.Transplant Proc . 2005 Jul-Aug;37(6):2574-5. doi: 10.1016/j.transproceed.2005.06.068
4.Srisuwarn P, Sumethkul V. Kidney transplant from donors with hepatitis B: A challenging treatment option. World J Hepatol 2021; 13(8): 853-867 [PMID: 34552692 DOI: 10.4254/wjh.v13.i8.853]
Thankyou vaccination policy is more significant than passive immunity with IvIG.
Please give more details for vaccination policy.
Will you accept this DBD donor?
Yes, I will accept the donor.
According to
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
This donor is HBsAg -ve, HBsAb -ve
HBcAb +ve
HBeAg and HBeAb -ve
So, this donor has either past HBV infection with no active infection at present or an occult infection.
The donor can be accepted even if recipient is HBcAb positive is when occult infection if ruled out or proper steps are taken to treat it.
So, additional tests would as below:
Monitoring for HBV Recurrence or De Novo Infection
HBV Vaccination
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
Well done.
1-Will you accept this DBD donor?
Yes; I will accept this DBD donor;
According to British Transplantation Society Guidelines:March 2018;
–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. (1A)
-When a HBcAb positive donor is used, lamivudine prophylaxis may be given for six months after transplantation, although the risk of transmission is very low. (2C)
2-Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
Yes; I will accept this donor;
Interpretation of current case; according his virology report
HBsAG negative , HBsAB negative , HBcAB positive,
HBeAG negative, HBeAb negative
HCV negative , HIV negative
-(This Doner has prior infection vs Ocult infection);
Past HBV infection;
-Defined by the coexistence of anti-HBs and IgG anti-HBc.
Occult HBV infection;
-Defined by persistence of low level of intrahepatic HBV DNA without detectable HBsAg.
-It is a serological situation defned by the presence of isolated anti-HBc with the absence of HBsAg and antiHBs antibody.
-The detection of HBV DNA in the liver is the gold standard of diagnosis for occult HBV infection, however, gaining hepatic HBV DNA is diffcult in clinical setting since the procedure is invasive.
Isolated anti-HBc positive can be seen in three conditions.
*First, it can be predominantly seen as IgM class during the window period of acute phase.
*Second, after acute infection had ended, anti-HBs has decreased below the cutoff level of detection.
*Third, after several years of chronic HBV infection, HBsAg has diminished to undetectable levels.
-In these conditions, anti-HBc IgM should be checked in order to assess the possibility of recent HBV exposure.
Importance of diagnosis of occult HBV infection;
-It can be transmitted via transfusion, solid organ transplantation, or hemodialysis.
-Reactivation of HBV infection may occur in patients receiving chemotherapy or immunocompromised state.
-It may accelerate liver injury and lead to hepatic fibrosis in patients with chronic liver disease including chronic hepatitis C infection.
-It appears to be a risk factor for HCC by its carcinogenic effect and by leading to continuous hepatic inflammation and fibrosis.
-What will do for acceptance this doner;
-Further investigation;
(HBV DNA & Genotyping ,HDV serolog, anti HBc IM , U/S on Liver)
According to British Transplantation Society Guidelines: March 2018;
–Any potential transplant recipients found to be HBcAb positive but HBsAg negative (past infection) must have HBV DNA and HDV serology testing to exclude occult HBV or HDV infection. (1B)
–All donors who are positive for HBcAb but HBsAg negative (past HBV exposure) must have HBV DNA testing to exclude the possibility of occult HBV infection. (1C)
–Prophylactic anti viral treatment;
According to British Transplantation Society Guidelines: March 2018;
-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 a limited (6-12 months) course of prophylactic antiviral treatment; although monitoring for HBV recurrence is an equally acceptable strategy. (2B)
-Vaccination;
According to British Transplantation Society Guidelines: March 2018;
–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)
-Close Monitoring after KT;
According to British Transplantation Society Guidelines: March 2018;
-HBV DNA and HBsAg should be monitored every three months in the first year and thereafter every six months in individuals receiving a graft from a HBcAb positive donor, regardless of treatment or prophylaxis regimen. (1C)
-Monitoring intervals should be shortened in cases of self-reported or suspected non-adherence. (Not graded)
References;
-British Transplantation Society Guidelines: March 2018.
Raimondo G, Allain JP, Brunetto MR, et al. Statements from the Taormina expert meeting on occult hepatitis B virus infection. J Hepatol 2008;49:652-7.
-Raimondo G, Caccamo G, Filomia R, et al. Occult HBV infection. Semin Immunopathol 2013;35:39-52.
-Mahboobi N, Tabatabaei SV, Blum HE, et al. Renal grafts from anti-hepatitis B core-positive donors: a quantitative. review of the literature. Transpl Infect Dis 2012;14:445-51.
-Minuk GY, Sun DF, Greenberg R, et al. Occult hepatitis B virus infection in a North American adult hemodialysis patient population. Hepatology 2004;40:1072-7.
-Yoo JH, Hwang SG, Yang DH, et al. Prevalence of occult hepatitis B virus infection in hemodialysis patients. Korean J Gastroenterol 2013;61:209-14.
Clear,well done.
Will you accept this DBD donor?
Yes can accept this kidney keeping in mind patient’s isolated B core antibodies. HBc antibodies in absence of HBsAg have been reported in upto 20% [1] in endemic areas which could be due to;
· Anti HBs has fallen to undetectable level many years after recovery.
· HbcAb is a false positive.
· HbSAg titer is below detectable in chronic infection.
· Window period of acute hepatitis.
· False negative HbsAg.
Risk of HBV transmission from blood or organ donors with isolated core antibodies has been reported to be 0.4-78%. [2, 3]
Keeping all these possibilities in mind will have to explain to receipt and after consenting may proceed with transplantation and prophylactic antiviral therapy with close surveillance and treatment if infection occurs.
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
The above mentioned possibilities could be there so in case of live donor will have to do,
· Repeat testing for Anti HBc IgG and IgM (to exclude active infection along with Liver enzymes), HBsAg,ant HBs, HBe antibody.
· Liver function test and radiological scan to exclude chronic infection.
· DNA PCR
· Despite Negative DNA and no active hepatitis patient can develop de novo infection in up to 14% of liver recipients who received organ from isolated core antibody positive but negative HBsAg and negative DNA. [4]
· Risk of HBV infection would be there but keeping in mind dialysis related morbidity and mortality an individualized approach should be adopt and close surveillance for HBV infection after transplantation.
References
1. Lok AS, Lai CL, Wu PC. Prevalence of isolated antibody to hepatitis B core antigen in an area endemic for hepatitis B virus infection: implications in hepatitis B vaccination programs. Hepatology. 1988 Jul-Aug;8(4):766-70. doi: 10.1002/hep.1840080411. PMID: 2968945.
2. Lok AS, Lai CL, Wu PC. Prevalence of isolated antibody to hepatitis B core antigen in an area endemic for hepatitis B virus infection: implications in hepatitis B vaccination programs. Hepatology. 1988 Jul-Aug;8(4):766-70. doi: 10.1002/hep.1840080411. PMID: 2968945.
3. van de Laar TJ, Marijt-van der Kreek T, Molenaar-de Backer MW, Hogema BM, Zaaijer HL. The yield of universal antibody to hepatitis B core antigen donor screening in the Netherlands, a hepatitis B virus low-endemic country. Transfusion. 2015 Jun;55(6):1206-13. doi: 10.1111/trf.12962. Epub 2014 Dec 15. PMID: 25494685.
4. Bohorquez HE, Cohen AJ, Girgrah N, Bruce DS, Carmody IC, Joshi S, Reichman TW, Therapondos G, Mason AL, Loss GE. Liver transplantation in hepatitis B core-negative recipients using livers from hepatitis B core-positive donors: a 13-year experience. Liver Transpl. 2013 Jun;19(6):611-8. doi: 10.1002/lt.23644. PMID: 23526668.
Thank you for your reply. Please notice, it is a renal patient rather than a liver. I will wait for other colleagues to write their reflections.
yes professor HBV would remain in hepatocyte and de novo infection is plausible, but the point here was to highlight the importance of isolated core antibody positive associated risk.
Thank you for your input.
Will you accept this DBD donor?
Yes .
Will check Anti=Hbs titre in receipient and if >10 miu/ml then nucleotide prophylaxis is not needed post transplant.
If 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.
LFT and HBV DNA needs to be monitored every 3 monthly for a year and then yearly post transplant.
If Anti-Hbs titers <10 miu/ml then will need HBIG and post transplant nucleotide antiviral prophylaxis for 12 months .
LFT and HBV DNA needs to be monitored monthly for 3 months and then every 3 monthly for a year and then yearly.
Will you accept this donor as a live donor if the recipient is also HBcAb positive? If yes, what are the conditions that should be met?
Yes .
Transplant can go ahead with a single shot HBIG prophylaxis to reduce sero conversion or reactivation in a Hbc positive receipient.
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