1. You were offered kidneys from a 56 -year-old male DBD (donor after brain stem death) donor who suffered from SAH (grade 5) complicating cerebral aneurysm. His retrieval S Cr was 78 µmol/L. Virology was reported as follows: HBsAg negative, HBsAb negative, HBcAb negative, and both HBeAg and HBeAb are negative. HCV antibody is positive, but HCV PCR is negative. HIV is negative.
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Assuming HCV PCR is not available, how would you manage the case?
195 Comments
Mohammed Sobair
Will you accept this DBD donor?
Yes.
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Yes
Check donors is not cirrhosis or fibrosis ,consult. With hepatologist.
If time allowed treat the dojor.otherwise both will revived DAA therapy postransplant for 12 months.
Assuming HCV PCR is not available, how would you manage the case?
If not available or not known ,still donors could be accepted and HCV PCr foje pist trandplant to follow for infection.
Will you accept this DBD donor? Yes, I will accept if the following are met:
Recipient counselled regarding risk of transmission and he is accepting especially if he is in urgent need for a graft.
The recipient should have normal liver functions with no HBV co-infection
Standard immunological risk.
Pangenotypic DAAs available and can be afforded.
prophylactic treatment with Elbasvir/grazoprevir 2-3 months starting D-1 before transplantation. Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met? For living donor actually still minimal risk for cryoglobinemia even after treatment of HCV but if the donor still willing, I will accept if the following are met:
Recipient counselled regarding risk of transmission and he is accepting especially if he is in urgent need for a graft.
The recipient should have normal liver functions with no HBV co-infection
Standard immunological risk.
Pangenotypic DAAs available and can be afforded.
Both of them will be Compliant on antiviral drugs
Donors with history of treatment failure or relapse should be excluded (SVR should be achieved for at least 1year)
HCV related renal disease should be excluded
Assuming HCV PCR is not available, how would you manage the case?
I will manage the patient as a PCR positive case, thus should be excluded unless recipient is in urgent need for the graft
References I. KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease VOLUME 102 | ISSUE 6S | DECEMBER 2022 http://www.kidney-international.org
II. Patnaik R, Tsai E. Hepatitis C Virus Treatment and Solid Organ Transplantation. Gastroenterol Hepatol (N Y). 2022 Feb;18(2):85-94. PMID: 35505819; PMCID: PMC9053510.
It is well recognized that a subset of patients who contracts Hepatitis C virus (HCV) spontaneously clears the virus. Such individuals are anti-HCV antibody positive, yet HCV RNA PCR negative in the blood. While they have not been considered candidates for live kidney donation in the past, with the recent availability of novel anti-HCV drugs with >95% cure rates, they now represent a potential pool of donor candidates, especially since the risk for transmission of HCV to the recipient is extremely low. The investigators goal is to demonstrate that live kidney donation from anti-HCV positive, HCV RNA PCR negative individuals is safe and carries a negligible risk of viral transmission to the recipient.
· The picture in this scenario indicates either a false positive blood test that requires confirmation of a prior infection that has been resolved or treated(no current active infection and no viremia).
· Yes, I will accept this donor with hepatitis C Abs positive and HCV PCR negative in view of low-risk of transmission (HCV positive donors can be accepted regardless of the HCV status of the potential kidney transplant recipient).
· Proper counseling and consenting of the recipient and follow up after 12 weeks post transplantation is required with NAT testing to confirm absence of the transmission that requires treatment. If the HCV PCR became positive, the patient should be treated with directly acting antivirals for 12 weeks.
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
· Yes, I will accept this donation( donor with no active disease or viremia) as HCV positive donors can be accepted regardless of the HCV status of the potential kidney transplant recipient.
· Conditions to be met: · The donor does not have any cirrhotic changes after evaluation by the hepatologist and does not have any extra-hepatic renal manifestations like proteinuria or hematuria that indicates the presence of GN as MPGN, cryoglobuleinemia or membranous nephropathy. · Donors with positive PCR(not in this scenario) should undergo HCV treatment before donation if the recipient is HCV-uninfected and they can be accepted for donation if they achieved a SVR.
Assuming HCV PCR is not available, how would you manage the case
· In HCV PCR is not available for any cause, I will consider the donor as positive PCR for HCV. I will check HCV PCR in the post-transplant period at day 3-day7 and day10 -day14 and 6weeks post-transplant, if remained negative, I will reassure the patient. Otherwise, i will initiate DAAs in the early post-transplant period. Transplantation of HCV-viremic organs into HCV-naive recipients followed by the use of DAA agents provides excellent patient and allograft survival.
References:
1. Kidney Disease: Improving Global Outcomes (KDIGO) Hepatitis C Work Group. KDIGO 2022 Clinical Practice Guideline FOR the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease. Kidney Int. 2022 Dec;102(6S):S129-S205.
2. Fontaine H, Alric L, Labreuche J, Legendre B, Louvet A, Antoine C, Legendre CM, Hazzan M, Kamar N, Dharancy S, Pol S, Duhamel A, Mathurin P. Control of replication of hepatitis B and C virus improves patient and graft survival in kidney transplantation. J Hepatol. 2019 May;70(5):831-838.
1. Ans; yes I will accept. As there is evidence of no any active infection. 2. Ans; yes, As the donor still does not have infectivty and state no evidence of cirrhosis, and associated secondary other renal disease. As per KDIGO guidelines HCV positive can donate organ. Just to confirm the genotype for further treatment. 3. Ans; I will council the family for possible risk of HCV contamination, will follow with LFTs, ultrasonography of upper abdomen, and repeated HCV PCR test. If any infection will start treatment.
Will you accept this DBD donor? I will accept him. He has negative hepatic virology profile except for positive HCV antibody but HCV PCR is negative . Which means he might have previous infection that was cleared spontaneously or with TTT and now he is not infective and no viral load detected and no risk of infection transmission. occult HCV infection”- the presence of HCV RNA in peripheral blood mononuclear cells and organ tissue by ultrasensitive assays in the absence of detectable RNA in the serum. However, this entity is itself controversial, and its significance is uncertain, with inadequately described risk of transmission.
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Yes I will accept him also. In the past it was contraindicated but now with advances on DAAS treatment the current cure rates for HCV now exceed 95%. A recent report demonstrated high cure rates even in the liver transplant setting, suggesting that immunosuppression does not impede eradication and that interactions between HCV and transplant drugs can be successfully managed. But her as the donor is living both should receive treatment for HCV before transplantation, treated with sofosbuvir and ribavirin for 12 weeks. . A group in Barcelona reported transplantation of a live donor kidney from a donor treated with an anti-HCV regimen that achieved a sustained virological response to her spouse with no transmission of infection. It is also recommended to treat HCV infection before transplantation to reduce the risk of liver cirrhosis and HCV-associated renal disease ( such as cryoglobulinemia ). Assuming HCV PCR is not available, how would you manage the case? If HCV RNA by PCR of the donor is unavailable we can still proceed for transplantation with monitoring of recipient HCV RNA by PCR if infection transmition occurred ,start anti-viral ttt
References:
Live Kidney Donors with Positive Anti-HCV Antibody, But Negative HCV PCR. ClinicalTrials.gov Identifier: NCT02669966. 2020
Yes, i would accept this DBD donor as risk of HCV transmission is low
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Yes, i would accept this donor as a live donor if the recipient is also HCV positive.
At first treatment of HCV positive recipient with DAA after genotype assessment. When HCV RNA undetectable then go for transplantation. Then do HCV PCR of the recipient on post transplant 3-7 day, 10-14 day and 6 weeks. If HCV PCR negative then reassure patient. If HCV PCR positive then start DAA within 3-10 working days
Assuming HCV PCR is not available, how would you manage the case?
Assume that donor is HCV positive and start peri operative DAA.
Will you accept this donor as a live donor if the recipient is HCV-positive? If yes, what are the conditions that should be met?
Yes,
However, we need to be sure that the donor has no evidence of liver cirrhosis and pristine urinalysis (no haematuria and no proteinuria) as the presence of these findings could suggest underlying renal pathology ie: MPGN, membranous, cryoglobulinaemia.
Assuming HCV PCR is not available, how would you manage the case?
Assume the donor PCR is positive and treat the recipients with DAA pre or immediately after transplantation (a few hours before to a median of 76 days after transplantation) (1)
References
Fabrizi F, Cerutti R, Alfieri CM, Messa P. Updated View on Kidney Transplant from HCV-Infected Donors and DAAs. Pharmaceutics. 2021 Apr 6;13(4):496. doi: 10.3390/pharmaceutics13040496. PMID: 33917382; PMCID: PMC8067384.
Q1: Yes, I will proceed to transplantation, because positive serology with negative PCR for HCV, only indicates previous infection of HCV. According to KDIGO guideline, HCV-infected donors could be considered for TX with DAA therapy.
Q2; Yes, I will. According to KDIGO guideline, HCV positive donors regardless of the HCV status of the recipients, could donate their kidney.
HCV positive individuals, could donate their kidney only if:
1. Start the HCV treatment before TX, if the recipient is HCV negative.
2. There is no cirrhosis in the donor.
Q3: In this situation, it is better to consider the donor’s PCR positive. So, I will start treatment with DAA therapy and follow- up with repeated HCV PCR test after transplantation. Patient and graft survival are very good in HCV positive donors among recipients, but needs adequate information and informed consent.
Reference:
1.Jadoul, M., Awan, A. A., Berenguer, M. C., Bruchfeld, A., Fabrizi, F., Goldberg, D. S., Jia, J., Kamar, N., Mohamed, R., Pessôa, M. G., Pol, S., Sise, M. E., & Martin, P. (2022). KDIGO 2022 Clinical Practice Guideline FOR the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease. Kidney International, 102(6).
2.Patnaik, R., & Tsai, E. (2022). Hepatitis C Virus Treatment and Solid Organ Transplantation. In Gastroenterology and Hepatology (Vol. 18, Issue 2).
The patient is offered a kidney from a 56 year old male DBS with no evidence of HBV or HIV…. The donor has negative HCV RNA PCR and anti HCV antibodies…This case has previous HCV infection in the past the details of which we are not able to elicit…I will accept this donor as there is low risk of transmission due to negative HCV RNA level….I will counsel the recipient for possible monitoring of the HCV viral load and initiation of DAA in the future if there is HCV RNA reactivation…weekly HCV RNA levels on day 7, 14 and 6 weeks post transplant.. KDIGO recommends to take the organ from HCV Positive donor regardless to the status of HCV of recipient
Will you accept this donor as a live donor if the recipient is also HCV positive?
HCV positive donor is giving the kidney to HCV positive recipient…HCV positive donors can be accepted regardless of the state of HCV positive state of the recipient as per KDIGO guidlelines….The donor should be evaluated for the presence of HCV genotyping to decide on antivirals if the HCV RNA quantitative is positive..USG abdomen for coarse echoes and fibroscan to rule out cirrhosis is a must..Living donation can be proceeded in the absence of fibrosis..IF the HCV RNA of the donor is positive and the recipient is negative the Live donor should be started on DAA. In this case the donor HCV RNA is negative, and donor need not be treated with DAA….
The recipient has to be evaluated in detail by LFT, Fibroscan, OGD scopy, Anti HCV status, HCV RNA quantitative analysis has to be done to rule out cirrhosis..F1,F2 fibrosis by fibroscan can be proceeded with kidney transplant alone and F3,F4 fibrosis needs combined liver and kidney transplant…
If both donor and recipient are HCV infected, DAA treatment of the donor can be delayed….if HCV RNA of the recipient is negative, donor due HCV has to be started on DAA immediately …
With the advent of DAA, it can be continued in the post transplant period with no interaction with immunosuppression….
Assumuing HCV PCR is not available, how would you manage the case? If the donor HCV PCR is not available, transplant can be proceeded with recipient testing for HCV RNA at a regular basis that is day 3, day 7, day 14 and after 6 weeks after transplant….
KDIGO guidelines – Hepatitis C workup group KDIGO 2022
Yes, because this serological status and PCR indicate that the patient has already had the disease and is cured.
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Yes, that would be really nice. I would only try to perform HCV treatment prior to transplantation, but it could also be performed subsequently.
Assuming HCV PCR is not available, how would you manage the case?
– A discussion with family members about the risks of HCV contamination would be necessary
– Conducting serial liver function tests, anti-HCV and PCR for HCV in the post-transplant period
– Execution of treatment if the receiver evolved with signs of HCV viral replication.
References:
– KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease VOLUME 102 | ISSUE 6S | DECEMBER 2022 http://www.kidney-international.org
– Patnaik R, Tsai E. Hepatitis C Virus Treatment and Solid Organ Transplantation. Gastroenterol Hepatol (N Y). 2022 Feb;18(2):85-94. PMID: 35505819; PMCID: PMC9053510.
1.Will you accept this DBD donor? – Yes, it is well acceptable – HCV Ab + / HCV RNA negative: indicate previous antiviral treatment or spontaneous clearance of the virus with increased immunity or even false positive results – The chance of HCV transmission is very low, compared to those with RNA positive – Outcomes even for HCV negative recipients favourable; it increased the organ pool and waiting time for HCV positive are as well as negative recipients. – The recipient has to be counselled about the risk of HCV, need for antiviral treatment, high risk of graft dysfunction and mortality. – But survival and QOL of patients received organs from HCV+ donors are far better than those on dialysis and waiting list. – Checking for HCV-RNA -PCR results à positive viremia needs 12 weeks antivirals; if negative à no antiviral therapy, but monitoring every 3months. 2. Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met? – yes, HCV+ donor for HCV+ recipient is acceptable; – HCV infection in the potential kidney transplant recipient is not a contraindication to transplantation, as effective antivirals are available for both Pre- and Post transplant. – In case of live donor with HCV+, we can have time to better the donor till the virus is undetectable before transplant. – Higher risk of Hepatitis, renal allograft graft dysfunction / rejection and mortality, need to be explained. – DAA -HCV-antiviral is effective and safe. 12weeks antiviral treatment started within hospital, post-transplant is recommended and SVR rate is nearly 100%. – Need to ensure affordability and access to DAA · Measures to avoid unfavourable outcomes: – Staging of Liver disease (extent of fibrosis) in recipient – through APRI score (AST-to-platelet ratio index) and transient elastography (TE) which estimates the liver stiffness. – liver biopsy is reserved for discordant non-invasive test results or when suspecting liver comorbidities – Cirrhotic patients, need assessment of portal Pressure, to rule out PHT Ø Chronic Hepatitis and compensated Cirrhosis with Portal Pressure <10, advised for antiviral treatment with Kidney transplant. Ø Decompensated liver disease, compensated liver cirrhosis with severe portal hypertension à need combined liver-kidney transplant (decompensated liver disease is characterized by decreased serum albumin and/ or hyperbilirubinemia, prolonged INR, ascites, hepatic encephalopathy
Direct Acting Antiviral treatment –
o Ensure reliable access to DAA · timing of DAA therapy – Treatment prior to transplant, if the patient has severe liver disease (e.g., decompensated liver cirrhosis), rapidly progressive liver disease, extrahepatic complications of HCV infection, lack of access to organs from donors with HCV infection, long anticipated waiting time on the transplant, living donor. – If well matched cadaver organ is available right way, patient can go for renal transplant with early start of antiviral (-12 / 0 hour) – Anti-viral Regimen depends on the HCV genotype – antiviral treatment history, underlying liver disease, drug-drug interactions, cost, availability. – Expert Hepatologist should be taken on board for treating such cases – Sofosbuvir has no drug-drug interactions with CNIs, MMF or mTORi, and has good SVR (90-98%) rate – Monitoring for HCV-related kidney disease and liver disease – atients with advanced fibrosis or cirrhosis have increased risk for HCC – AFP and Liver USG every 6months is recommended – Surveillance for Renal and Liver problems as well as NODAT and PTLD Assuming HCV PCR is not available, how would you manage the case? – We have to consider him as HCV-RNA positive donor – Counselling the recipient regarding the high risk of transmission and hence the need to start DAA therapy prior to transplantation (-12hr or 0-hr) References
1. Terrault, Norah A. et al. International Liver Transplantation Society Consensus Statement on Hepatitis C Management in Liver Transplant Recipients. Transplantation 2017 May;101 (5): 956-967 2. Patnaik R, Tsai E. Hepatitis C Virus Treatment and Solid Organ Transplantation. Gastro-enterlogy & Hepatology issue 2. February 2022. Gastroenterology & Hepatology 2022 Feb; 18 (2): 85-94 3. Jandovitz N, Nair V, Grodstein E, Molmenti E, Fahmy A, Abate M, et al. Hepatitis C-positive donor to negative recipient kidney transplantation: A real-world experience. Transplant infectious disease : an official journal of the Transplantation Society. 2021 Jun;23(3):e13540. PubMed PMID: 33259125. Epub 2020/12/02. Kamalkiran M, Ravikiran V, Shashidhar C, Prasad KVR, Yeldandi V. Kidney Transplantation from a Hepatitis C Virus-positive Donor to a Hepatitis C Virus-negative Recipient. Indian journal of nephrology. 2018 Nov-Dec;28(6):488-9. PubMed PMID: 30647508. Pubmed Central PMCID: PMC6309394. Epub 2019/01/17. 4. Pestana NF, Equi CMA, Gomes CP, et al. Aminotransferase-to-platelet ratio index and Fibrosis-4 index score predict hepatic fibrosis evaluated by transient hepatic elastography in hepatitis C virus-infected haemodialysis patients. European journal of gastroenterology & hepatology 2021 Dec;33(1S) Suppl: e260-e5. PubMed PMID: 33405422. Epub 2021/01/07. 5. Kiberd BA, Doucette K, Vinson AJ, Tennankore KK. Hepatitis C virus-infected kidney waitlist patients: Treat now or treat later? American journal of transplantation 2018 Oct;18(10): 2443-50. PubMed PMID: 29687948. Epub 2018/04/25. 6. KDIGO 2018 clinical practice guideline for the prevention, diagnosis, evaluation, and treatment of hepatitis C virus in chronic kidney disease What is the chance of transmission of HCV in HCV antibody positive, HCV PCR negative? · HCV Ab + / HCV RNA negative: indicate previous antiviral treatment or spontaneous clearance of the virus with increased immunity or even false positive results · The risk of HCV transmission in this case is very low, compared to those with RNA positive. · The risk of transmission is non with HCV Ab negative + HCV RNA negative. Ref: Patnaik R, Tsai E. Hepatitis C Virus Treatment and Solid Organ Transplantation. Gastro-enterlogy & Hepatology issue 2. February 2022. Gastroenterology & Hepatology 2022 Feb; 18 (2): 85-94 Is it important to check urine for proteinuria and haematuria for donor who had HCV infection? Why? Yes Donors with HCV infection – it is important to rule out HCV related nephropathies Common glomerularpathologies – Mixed cryoglobulinemia, MPGN, Membranous glomerulonephritis. MPGN is most commonly associated with HCV infection Less common pathologies – Membranous nephropathy (MN), FSGS, Thrombotic microangiopathies (TMAs), IgA nephropathy (IgAN) Clinical Presentation – proteinuria, microscopic haematuria, hypertension, acute nephritis and nephrotic syndrome Reference: 1. Ozkok A, Yildiz A. Hepatitis C virus associated glomerulopathies. World J Gastroenterol. 2014 Jun 28;20(24):7544-54. doi: 10.3748/wjg.v20.i24.7544. PMID: 24976695; PMCID: PMC4069286. 2. Johnson RJ, Willson R, Yamabe H, Couser W, Alpers CE, Wener MH, Davis C, Gretch DR. Renal manifestations of hepatitis C virus infection. Kidney Int. 1994 Nov;46(5):1255-63. doi: 10.1038/ki.1994.393. PMID: 7853784. 3. Latt N, Alachkar N, Gurakar A. Hepatitis C virus and its renal manifestations: a review and update. Gastroenterology & hepatology. 2012 Jul;8(7):434-45. PubMed PMID: 23293553. Pubmed Central PMCID: PMC3533219. Epub 2013/01/08.
4. Markowitz GS, Cheng JT, Colvin RB, Trebbin WM, D’Agati VD. Hepatitis C viral infection is associated with fibrillary glomerulonephritis and immunotactoid glomerulopathy. Journal of the American Society of Nephrology: JASN. 1998 Dec;9(12):2244-52. PubMed PMID: 9848778. Epub 1998/12/16.
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Donors liver status should be assessed. An ultrasound followed by a Fibroscan is needed to clarify the liver status.
If there is no advanced liver disease this living donor should be accepted.
Assuming HCV PCR is not available, how would you manage the case?
we should consider it as HCV positive and will treat with DAA in post transplant period
Will you accept this DBD donor?
· Yes. According to KDIGO 2022: They recommend that kidneys from HCV-infected donors be considered regardless of HCV status of potential kidney transplant recipients.
· Transplant centers must ensure that patients receive education and are engaged in discussion with sufficient information to provide informed consent.
· Patients should be informed of the risks and benefits of transplantation with an HCV infected kidney, including the need for DAA treatment
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
· Yes, as kidney transplantation is the best therapeutic option for patients with CKD G5 irrespective of the presence of HCV infection.
· kidney transplant candidates with HCV should be evaluated for severity of liver disease and presence of portal hypertension prior to acceptance for kidney transplantation
· Patients with HCV, compensated cirrhosis, and no portal hypertension undergo isolated kidney transplantation and patients with decompensated cirrhosis or clinically significant portal hypertension undergo a simultaneous liver–kidney transplantation
· HCV-infected kidney transplant candidates with a living kidney donor should be treated with DAA therapy before or shortly after transplantation depending on the anticipated timing of transplantation
Assuming HCV PCR is not available, how would you manage the case?
· If PCR not available he should be treated as HCV + with DAA.
KDIGO 2022 CLINICAL PRACTICE GUIDELINE FOR THE PREVENTION, DIAGNOSIS, EVALUATION, AND TREATMENT OF HEPATITIS C IN CHRONIC KIDNEY DISEASE
Yes, this DBD donor would be accepted.
Patient with HCV antibody indicates previous infection.
Donors who are HCV Ab positive are grouped as viremic and non-viremic based on NAT testing. Those with NAT positive are viremic. Those donors who are HCV Ab positive, but NAT negative can be transplanted to HCV negative recipients, but post-transplant NAT testing is recommended to confirm the lack of disease. In HCV negative recipients if de novo HCV infection occurs then direct antivirals should be started. Kidney from donors who are Hepatitis C Ab positive and NAT negative can be transplanted into HCV NAT positive recipients, DAA treatment should begin post-transplant. Although transplant between HCV NAT positive donors and HCV NAT positive recipients is recommended and post-transplant DAA treatment should be started with monitoring of PCR. Transplant of HCV NAT positive kidney to HCV negative recipient is possible with DAA treatment, and should be followed closely for potential complications.
DBD with -ve HBV and HCV antibody +ve with -ve PCR
Will you accept this DBD donor?
I will accept such donor as +ve HCV AB may due to previous infection or false +ve result.
A donor who is HCV antibody-positive/NAT-negative has an infection that spontaneously cleared or was successfully treated or a false-positive antibody result. Such patients have a very low risk of HCV transmission.
Furthermore, even at the list price of DAAs (the actual prices that the NHS pays are lower) the additional costs of transplanting recipients exposed to HCV with a kidney from a HCV antibody positive donor was cost-neutral in comparison with remaining on dialysis within 5 years following transplantation.
Recipient HCV PCR testing within 3 months of transplantation to monitor for HCV disease transmission.
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Yes I will accept this donor
MDT must be included ,,, hepatologist consultant for evaluation of patient and donor health status ,portal hypertension,hepatic fibrosis and if hepatic failure present to consider both hepatic and renal transplant .
Both recipient and donor should be start on DAA to prevent post transplant complications fibrosing cholestatic hepatitis ,vasculitis and PTLD.
Assuming HCV PCR is not available, how would you manage the case?
I will proceed transplant , HCV RNA may not yet be detectable and transplant recipients from these donors should be monitored for HCV in addition to HBV and HIV per the increased-risk donor testing protocols.
DAAs were initiated in a range between a few hours before renal transplant (RT) to a median of 76 days after RT.
Acceptance of the donor; yes based on the serology
Also, donation from HCV-infected live donor is accepted if HCV of the recipient is positive or negative serology with treatment of the donor prior to donation with achieving SVR to reduce the risk of hepatitis C associated nephropathy.
Testing of renal function, and testing for proteinuria and hematuria to rule out HCV related nephropathy for the donor prior to decide processing for transplantation.
-If HCV PCR not available:
Recipient with his family should be counselled regarding possibility of infection from HCV RNA Positive donor.
We should consider positive RNA by PCR for HCV and start DAA before transplantation. HCV RNA by PCR needs to be monitored at 7th day, 14th day and 6 weeks post-transplant and DAA continued till 2 weeks if positive.
References:
KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease Vol 102 | ISSUE 6S | DECEMBER 2022
Yes i will accepot this patient as a kidney donor as being HCv Ab positiv means that had the infection and now cleared or treated specially if his HCV RNA -.
We can accept this kidny without fear of HCV infection .
The estimated rate of spontanouse clearance is 20 to 45% depend on the age and immunity of the person .
There is a strong and likely causal association between chronic hepatitis C virus (HCV) infection and glomerular disease. ●The major glomerular diseases associated with HCV infection include the following •Mixed cryoglobulinemia syndrome •Membranous nephropathy •Polyarteritis nodosa (PAN)
All patients with mixed cryoglobulinemia syndrome, membranoproliferative glomerulonephritis (MPGN) type I, membranous nephropathy, and PAN should be evaluated for possible underlying HCV infection. In addition, HCV-infected patients should be evaluated for proteinuria, hematuria, hypertension, and a reduced glomerular filtration rate (GFR). Patients who are found to have kidney abnormalities should undergo testing for cryoglobulins, hypocomplementemia, and a positive rheumatoid factor. A kidney biopsy should be considered in the setting of significant proteinuria and/or impaired kidney function.
In general, patients with severe and progressive HCV-associated glomerulonephritis should undergo antiviral treatment. Most patients with less severe glomerular disease associated with HCV should also have antiviral therapy provided they do not have decompensated cirrhosis. In patients who are selected for antiviral therapy, the specific regimen depends upon the estimated GFR (eGFR).
1- I will accept him as the risk of transmission is low(seropositive but not viremic)
2- IF the recipient is positive:
We can accept the kidney
but requires:
evaluation of the PCR of the recipient
assessment of the liver condition including presence of cirrhosis and portal hypertension
in compensated liver disease: proceed for transplant with peri-transplantation antiviral therapy and monitoring of HCV PCR regularly post transplantation
in decompensated liver disease : require combined liver and renal transplantation.
3- IF PCR is not available:
1- send specimen for central labs and once result is available send to tx center
2- if other liver function of the donor is ok, we can accept it for suitable recepient
3- assessment of recipient HCV PCR:
after3-7 days
if negative repeat after 2 weeks
if negative repeat after 6 weeks
if negative reassess the recipient and manage as negative one
if positive at any time: start SOF-based treatment (Sofosbuvir/Velpatasvir) for 12 weeks
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Donors liver status should be assessed. An ultrasound followed by a Fibroscan is needed to clarify the liver status.
If there is no advanced liver disease this living donor should be accepted.
Assuming HCV PCR is not available, how would you manage the case?
we should consider it as HCV positive and will treat with DAA in post transplant period
considering D+ to R transplantation should be considered , across all solid organs within
set criteria, and recommended that such practice should take place within prospective research protocols.
the high morbidity and mortality rates for patients on the waiting list justify the utilisation of D+ organs.
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
viremic donor and a viremic recipient (D±/R+), DAA therapy in the posttransplantation
period should follow the policy of the transplant center, according to recent American
Association for the Study of Liver Diseases/Infectious Diseases Society of America and
transplant guidelines.
The use of HCV-viremic donors for HCV-viremic recipients (D+/R+) is acceptable in
routine clinical practice.
RFFRENCES:
1-Terrault, Norah A. et al .International Liver Transplantation Society Consensus Statement on Hepatitis C Management in Liver Transplant Recipients.Transplantation ,101(5):p 956-967, May 2017.
56 YR old male, DBD,SAH from cerebral aneurysm with a cr of 78
HBsAG ,HBcAB,HBeAG,HBeAB,HCV PCR,HIV -NEG,HCV ab +VE
Will you accept this donor?
Yes, this will decrease the waiting period and studies show good post transplant graft function. HCV is not a contraindication to donation and timing of treatment is determined on a case by case basis.
Will you accept this donor as a live donor if recipient too is HCV positive? If yes, what conditions should be met?
HCV is not a contraindication to transplant either as a recipient or donor and besides it is treatable with better outcome post transplant in comparison to hemodialysis.
Conditions to be met;
Stage the liver dx and asses for fibrosis and portal pressures, if no portal htn and the donor is available for >24 weeks, treat pre transplant, if not available ,tx post transplant. If portal pressures >10mmhg,evaluate for both kidney and liver transplant.
Ensure evaluation of meds availability, recipients compliance to treatment pre tran splant. Preferably pangenomic DAA to avert resistance and D-D-I with CNIs.
Screen and ensure no Hepatitis B coinfection.
Donor screening to ensure HCV associated nephropathy prior to Donation is absent. This should include a biopsy if urinalysis and urine protein are suggestive to R/O MPGN,FSGS,Membranous GN etc secondary to HCV.
Assuming HCV PCR is not available, how would you proceed?
I would treat him as a viremic donor with a high risk of transmission and start DAA prior to transplantation. Elbasivir/Grazoprevir OD for 2-3/12 beginning 1/7 pr transplant.
REF;
Paulina C et al;Utilization of viremic donors in kidney transplantation ;A chance or a threat.Pub med Dec 2022
KDIGO 2022 clinical practice guidelines for prevention, diagnosis, evaluation and treatment of Hep C in CKD.VOL102/ISSUE/65/DEC2022
Sawinsnki et al; Novel Hep C tx and impact on kidney transplantation.2015;1-9
1. You were offered kidneys from a 56 -year-old male DBD (donor after brain stem death) donor who suffered from SAH (grade 5) complicating cerebral aneurysm. His retrieval S Cr was 78 µmol/L. Virology was reported as follows: HBsAg negative, HBsAb negative, HBcAb negative, and both HBeAg and HBeAb are negative. HCV antibody is positive, but HCV PCR is negative. HIV is negative.
– use of such organs expands the organ pool and decreases the waiting times for HCV-negative recipients and is associated with favourable outcomes
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met? (1, 2)
– yes, I would accept the donor as a live donor if the recipient is also HCV positive
– HCV infection in the potential kidney transplant recipient is not a contraindication to transplantation
– HCV infection increases the morbidity and mortality post-kidney transplant
– HCV infection treatment is effective and safe
– to avoid unfavourable outcomes, some measures/ conditions have to be put into place: –
monitor kidney function and liver function
stage the liver disease (i.e., assess extent of fibrosis) through noninvasive techniques including blood tests and imaging tests e.g., APRI score which aspartate aminotransferase (AST)-to-platelet ratio index and transient elastography (TE) which estimates the liver stiffness (3)
– if cirrhosis is present, assess for portal hypertension prior to transplantation
– liver biopsy is reserved for discordant noninvasive test results or when suspecting liver comorbidities
type of transplantation i.e., kidney vs combined liver-kidney transplant this typically depends on whether the patients has compensated or decompensated liver disease
– decompensated liver disease is characterized by decreased serum albumin and/ or hyperbilirubinemia, prolonged INR, ascites, hepatic encephalopathy
– indications for a combined liver-kidney transplant: – decompensated liver disease, compensated liver cirrhosis with severe portal hypertension
antiviral treatment – ensure reliable access to DAA
– timing of DAA therapy – DAA can be given before or after transplantation depending on several factors
– offer treatment prior to transplant if the patient has severe liver disease (e.g., decompensated liver cirrhosis), rapidly progressive liver disease,extrahepatic complications of HCV infection, lack of access to organs from donors with HCV infection, long anticipated waiting time on the transplant, living donor (4)
– basically, the timing of DAA therapy relative to the transplant depends on the waiting list advantage and the impact of delay on HCV-associated mortality especially in those with advanced fibrosis and cirrhosis (4)
– regimen selection depends on the HCV genotype, antiviral treatment history, underlying liver disease, drug-drug interactions, cost, availability
– Sofosbuvir can be used in all stages of kidney disease including
during dialysis
– Sofosbuvir has not been shown to have significant drug-drug interactions with CNIs, mycophenolate or mTORi
– should be able to assess for sustained virological response (SVR)
– in addition to the standard care/ monitoring following transplantation, kidney transplant recipients with HCV infection require close monitoring for HCV-related kidney disease and liver disease until the HCV infection has been fully treated
– patients with advanced fibrosis or cirrhosis post-transplant are at increased risk for HCC hence should be continuously monitored for such complications
– test for proteinuria using spot uPCR or 24-hour urine protein, every 6 months
– new onset proteinuria (i.e., uPCR >1g/g or 24hr-urine protein >1g) or microscopic hematuria without any other identifiable cause warrants a graft biopsy for light microscopy, immunofluorescence and electron microscopy
– kidney disease associated with HCV infection among kidney transplant recipients includes: -MPGN, MN, transplant glomerulopathy, renal thrombotic microangiopathy
– other complications include PTDM, PTLD
Assuming HCV PCR is not available, how would you manage the case?
– I would consider him as a HCV-positive viremic donor
– I would inform and counsel the potential recipient regarding the high risk of transmission and hence the need to start DAA therapy prior to transplantation
References
1. Jandovitz N, Nair V, Grodstein E, Molmenti E, Fahmy A, Abate M, et al. Hepatitis C-positive donor to negative recipient kidney transplantation: A real-world experience. Transplant infectious disease : an official journal of the Transplantation Society. 2021 Jun;23(3):e13540. PubMed PMID: 33259125. Epub 2020/12/02. eng.
2. Kamalkiran M, Ravikiran V, Shashidhar C, Prasad KVR, Yeldandi V. Kidney Transplantation from a Hepatitis C Virus-positive Donor to a Hepatitis C Virus-negative Recipient. Indian journal of nephrology. 2018 Nov-Dec;28(6):488-9. PubMed PMID: 30647508. Pubmed Central PMCID: PMC6309394. Epub 2019/01/17. eng.
3. Pestana NF, Equi CMA, Gomes CP, Cardoso AC, Zumack JP, Villela-Nogueira CA, et al. Aminotransferase-to-platelet ratio index and Fibrosis-4 index score predict hepatic fibrosis evaluated by transient hepatic elastography in hepatitis C virus-infected hemodialysis patients. European journal of gastroenterology & hepatology. 2021 Dec 1;33(1S Suppl 1):e260-e5. PubMed PMID: 33405422. Epub 2021/01/07. eng.
4. Kiberd BA, Doucette K, Vinson AJ, Tennankore KK. Hepatitis C virus-infected kidney waitlist patients: Treat now or treat later? American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2018 Oct;18(10):2443-50. PubMed PMID: 29687948. Epub 2018/04/25. eng.
KDIGO 2018 clinical practice guideline for the prevention, diagnosis, evaluation, and treatment of hepatitis C virus in chronic kidney disease
Will you accept this DBD donor?
Yes I will accept this donor.
The donor is HCV antibody positive with negative PCR hence this donor had HCV infection and was treated successfully thus has no risk of transmission.
The HCV antibody can remain positive indefinitely.
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Yes I would accept if this was living donation and both donor and recipient are positive.
The conditions to be met include:
The donor since had prior infection and was successfully treated should avoid any risky behaviour that would expose them to reinfection.
ideally the recipient should be treated prior to transplantation.
Both donor and recipient should not have liver cirrhosis
DAA should be started promptly after transplantation for a period of 12 weeks.
Assuming HCV PCR is not available, how would you manage the case?
If the HCV PCR is not available it would be difficult to know whether the donor has acute infection or past infection which will translate to the risk of transmission.
I would continue with transplantation and counsel the recipient on the risk of HCV transmission.
If the recipient was HCV negative then HCV per would be done routinely in the post-transplantation period starting from 33-7 days post transplant, then 10-14 days post transplant and 6 weeks post transplant.
A positive PCR will warrant prompt initiation of DAA the preferred combination will be Glecaprevir/Pibrenatasvir or Sofosbuvir/Velpatasvir which are pan-genotypic and have minimal drug interaction.
Other tests that could be done include NAAT and antigen testing.
What is the risk of transmission of HCV in HCV antibody positive and HCV PCR negative?
The risk of transmission is low.
A positive HCV antibody and negative PCR indicates either a false positive test, or a patient who was successfully treated.
However in a small proportion of patients may be in the window period or reinfection posing a high risk of transmission.
Is it important to check for urine proteinuria and hematuria in a patient who had HCV infection?
Yes, to look for extra hepatic manifestation of HCV infection that include cryglobulinaemic vasculitis, membranous nephropathy, MPGN.
References
KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease VOLUME 102 | ISSUE 6S | DECEMBER 2022 http://www.kidney-international.org
UK Position Statement on the use of Organs from Hepatitis C Viraemic Donors and Increased Infectious Risk Donors in Hepatitis C Negative Recipients
Donor is HCV antibody positive but HCV PCR negative. Thus risk of disease transmission from donor to recipient is very low post transplant. Thus I would accept this donor.
If donor had HCV antibody positive along with HCV PCR negative, then it means the donor has an active infection, and risk of disease transmission from donor to recipient post transplant would be 100%.
However, in our scenario, since the donor is HCV PCR negative, he has had a previous HCV infection which is not active at present, and would pose very low percentage of risk for transferring to the recipient post transplant.
Patient should however be monitored closely for HCV infection and given appropriate antiviral therapy since occult infection can occur.
Live donor, HCV positive recipient
Yes, I would accept this donor.
Donor has to be treated for HCV with DAAs prior to the transplant and check for viral load, along with sustained virologic response according to KDIGO guidelines (2018).
KDIGO guidelines also recommend pairing NAT positive live donor with NAT positive recipient to limit risk of HCV transmission and loss of organs from the donor pool. Both donor and recipient need to be treated appropriately with DAAs.
HCV positive recipients with compensated cirrhosis but without portal hypertension may be treated with DAAs post transplant if they have access to a living kidney donor without a long wait time.
Management if HCV PCR is not available
In the case that HCV PCR is not available, it is difficult to ascertain whether the donor has an active infection (in which case it is 100% transferable to recipient) or only had a previous infection which was treated with antiviral therapy.
I would counsel the recipient about the risk of transmission potentially, and ask for informed consent. I would accept this donor if the recipient has been on the waitlist for a few years and is eager to get transplanted and given that we cannot find any other suitable donor.
The recipient would need antiviral therapy post transplant for 8-12 weeks assuming that transmission of HCV infection has taken place from the donor. HCV PCR has to be done intermittently in this 12 week period.
References
KDIGO 2018 clinical practice guideline for the prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease. Journal of International Society of Nephrology. 2018; 8(3)
Liyanage L, Muzaale A, et al. Living kidney donation in individuals with hepatitis C and HIV infection : rationale and emerging evidence. Curries Transplant Rep. 2019; 6(2) : 167-176. doi: 10.1007/s40472-019-00242-5
Rawashdeh B, Hulse J, et al. Transplant of a kidney from a hepatitis C viremic donor to a naive recipient without viral transmission : a case report. Am J Case Rep.2021; 22:e927532-2-e927532-4. doi: 10.12659/AJCR.927532
= Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
**Yes
**conditions: No signs of nephopathy and donnor receives DAA 12 weeks prior to Tx to minimize the risk of transmission. Recipient should have surviellence post transplant and provide informed consent.
= Assuming HCV PCR is not available, how would you manage the case? will go a head and do HCV PCR at 3-7 days post Tx, repeated by day 10-14, then by 6 weeks post-transplant, if negative reassurance and no need for DAA therapy, if positive at any stage of screening, then start DAA within 3-10 days of positive test for 12 weeks, and confirm sustained viral response.
Yeas I will accept.
This donor had : HBsAg negative, HBsAb negative, HBcAb negative, and both HBeAg and HBeAb are negative but he had positive HCV antibody with negative HCV PCR which may be occult HCV infection within denoted organ which can activated after immune supressions ,therefor HCV investigations must be done after transplantation, if positive treatment must given.
Also HCV antibody positive may false positive result.
Over all this case is very low risk of transmission. Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Yes I will accept.
Exclude liver cirrhosis and HCC in both
Rule out CKD in donor
Available DAA for both donor and recipient
Informed consent
Negative PCR
Treatment of donor pre donation with sustained virologic response Assuming HCV PCR is not available, how would you manage the case?
Enzyme immunoassay can be done if NAT is not available
Short course of DAAT regimen can be given and SVR assessed Reference
Kidney Disease: Improving Global Outcomes. KDIGO clinical practice guidelines for the
prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease.
Kidney Int. 2008; 73 (suppl 109):S1–S99
All donors should be screened for HCV using both anti-HCV antibodies and PCR
Active donor HCV infection is considered a contraindication to donation, due to the fear of transmission of HCV from the donor to the recipient and this was accepted only if the recipient is HCV positive
If donor anti-HCV Abs (+), PCR (-) this means either spontaneous resolution of HCV (occur in 42% of cases but not common in immunocompromised individuals) or resolution after treatment, this type of donation is associated with seroconversion but minimal viremia.
If donor anti-HCV Abs (+), PCR (+) this denotes active viremia and this type of donation is associated with high risk of transmission and viremia
D+/R- transplantation is associated with 100% viremia of the recipient detected early after transplantation, so carry the highest risk
Approach for transplanting kidney from HCV + donor to HCV – recipient
The main challenge is transmission of HCV from donor to the recipient with possibility of HCV related hepatic affection and extra hepatic complications including GN, so the following approach should be done in order to improve outcome:
Selecting appropriate donor
Treatment of the donor and providing cure (SVR) for 1 year before transplantation is the best, this may be applicable in live and not in deceased donor
It is better to know the genotype of the donor since genotypes 1a and 3 are associated with treatment failure especially if pangenotypic DAAs are not available
Donors with history of treatment with NS5 inhibitors or history of relapse should be excluded
HCV related renal disease should be excluded
Selecting appropriate recipient
Recipient should be willing to take an infected kidney; it was found that 80% of recipient accepts receiving infected kidney while 18 % were not accepting
Compliance to antiviral drugs and follow up should be ensured
The recipient should be in urgent need for a graft such as 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 and better normal fibroscan
Standard immunological risk status is required to avoid aggressive immunosuppression. CNI, steroids, MMF and induction either by basiliximab or ATG is accepted (high risk transplant recipients which need desensitization should be excluded)
Recipient should not have HBV co-infection
Use of prophylactic therapy including Elbasvir/grazoprevir and /or sofosbuvir in D+R- status
Pangenotypic DAAs (Elbasvir/grazoprevir) are the preferred antiviral agents but the problem is the cost and availability
Sofosbuvir is the most effective agent for genotype 3 and now it is accepted to be given at GFR below 30 and in those of HD
Different protocols available according to different studies:
Prophylactic therapy : some studies reported SVR using prophylactic dose of Elbasvir/grazoprevir (one tablet daily) and sofosbuvir (only for those with genotypes other than 1 ) started 1 day before transplantation and continued for 3 months. One trial use prophylactic treatment for only 2-4 doses of Elbasvir/grazoprevir , one dose before and the remaining after transplantation, viremia occur in 30% and 7.5% of patients receiving 2 and 4 days protocol, and SVR was achieved in 83% of cases
Early treatment : One study found that SVR occur at 6 and 12 months after 3 months treatment with Elbasvir/grazoprevir started after detection of viremia (3 days after transplantation), other trials delay the treatment to 2 weeks post transplantation and some reduce the duration of treatment to 8 weeks and 4 weeks, and also all patients attain SVR.
Late treatment : one study delays the treatment for 76 days after transplantation (due to an insurance issue) and was associated with more complications.
To conclude … 3 protocols are available, prophylactic therapy, early treatment and late treatment. Late initiation of treatment is associated with the worst outcome since it is associated with viremia related complications, on the other hand prophylactic treatment leads to giving treatment to patient that may not require.
Monitoring
Regular check of serum ALT, HCV PCR post transplantation
Monitoring of proteinuria and kidney function
Monitoring of drug – drug interactions, Pangenotypic DAA regimens was found to have limited drug -drug interactions with CNI, on the other hand non- Pangenotypic DAA may reduce CNI level.
Will you accept this DBD donor?
Yes I will accept if the following are met:
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 not have HBV co-infection (HBV is negative for the current patient)
Pangenotypic DAAs should be available as to avoid resistance and for better drug-drug interaction with CNI
It is better to know the genotype of the donor since genotypes 1a and 3 are associated with treatment failure especially if pangenotypic DAAs are not available
Donors with history of treatment with NS5 inhibitors or history of relapse should be excluded
HCV related renal disease in the donor should be excluded
And I will initiate either prophylactic treatment with Elbasvir/grazoprevir once daily for 2-3 months starting from day -1 before transplantation or upon detection of viremia with regular check of serum ALT, HCV PCR, renal functions, proteinuria post transplantation and keep in mind drug-drug interaction when using non- Pangenotypic DAA
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Yes I will accept if the following are met:
Compliance to antiviral drugs and follow up should be ensured
Patient should not be in decompensated liver failure, as he/she will be a candidate for dual liver and kidney transplantation
Standard immunological risk status is required to avoid aggressive immunosuppression.
Recipient should not have HBV co-infection
Pangenotypic DAAs should be available as to avoid resistance and for better drug-drug interaction with CNI
It is better to know the genotype of the donor since genotypes 1a and 3 are associated with treatment failure especially if pangenotypic DAAs are not available
Donors with history of treatment with NS5 inhibitors or history of relapse should be excluded
HCV related renal disease should be excluded
And I will initiate either prophylactic treatment with Elbasvir/grazoprevir once daily for 3 months starting from day -1 before transplantation with regular check of serum ALT, HCV PCR, renal functions, proteinuria post transplantation and keep in mind drug-drug interaction when using non- Pangenotypic DAA.
Assuming HCV PCR is not available, how would you manage the case?
I will manage the patient as a PCR positive case, thus should be excluded except if the recipient is in urgent need for the graft and is desperate for the graft
At that time I will explain the possible risk of HCV related liver and kidney complications and possibility of graft and patient loss
And I will give prophylactic treatment with Elbasvir/grazoprevir once daily for 2-3 months starting from day -1 before transplantation
References
1- Utilization of HCV viremic donors in kidney transplantation: a chance or a threat?
This status may indicate previous treatment or spontaneous clearance of the virus or even false positive results and the chance of transmission is actually low compared with the other donor status e.g., HCV Ab positive + HCV NAT positive or HCV NAT positive + HCV Ab negative. The risk of transmission is non with HCV Ab negative + HCV NAT negative.(Ronit Patnaik and Eugenia Tsai Gastroenterlogy & hepatology issue 2. February 2022)
Thanks; Our Prof. -Clinical Interpretation of case with HCVAb (positive) /HCV PCR (negative);
-In this situation, the reactive anti-HCV antibody most likely represents prior infection that subsequently cleared spontaneously (or following successful therapy) or a false-positive antibody test due to technical reasons.
-False-negative tests for RNA are unusual when sensitive quantitative or qualitative tests with a low level of detection (eg, <25 international units/mL) are used.
-The absence of detectable HCV RNA essentially confirms the absence of chronic HCV infection.
-The estimated rate of spontaneous clearance of virus after infection is 20 to 45% depending upon the age and immune status of the individual at the time of infection.
(With low risk of transmission)
-The seroprevalence of HCV infection in the general population is approximately 1 to 3 % worldwide, although prevalence varies from region to region.
-However, before HCV RNA testing became mandatory, HCV positivity was defined only by HCV seropositivity, without consideration of the patient’s viremic status.
-Recipients of HCV-seropositive/RNA-negative kidneys appear to have the same graft and patient survival as recipients of HCV-seronegative kidneys. Rationale;
-HCV seropositivity does not necessarily mean HCV RNA positivity, which indicates an active replicating infection.
-The best data regarding prevalence among deceased organ donors are from a study of 13,667 potential organ donors evaluated between 2004 and 2008 by 17 organ procurement organizations in the United States; HCV seroprevalence was 3.45% among normal-risk potential donors and 18.2 % among high-risk potential donors.
-In one study of 55 living, related potential donors, the seroprevalence of HCV was 3.6 %.
-The reported seroprevalence of HCV infection among kidney transplant recipients is approximately 1.8 to 8 %.
-In one report that included 468 HCV-seropositive recipients, 5- and 10-year survival were not different between recipients of kidneys from HCV-seropositive and HCV-seronegative donors. References;
-HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C. Joint panel from the American Association of the Study of Liver Diseases and the Infectious Diseases Society of America.(Accessed on January 01, 2020).
Seropositive HCV (HVCAb+/RNA-)differs from viremic patient in risk of transmission, seropositive HCV had no documented risk of HCV infection transmission.
In a scenario with positive HCV antibody and a negative HCV PCR, the implication iseither a false positive anti-HCV antibody, or a past infection which either got cleared spontaneously, or after being treated.
Organs from such patients can be safely used without any increased risk of HCV transmission (1,2). The risk of transmission can be there in case the HCV PCR is falsely negative (3).
References:
Kidney Disease: Improving Global Outcomes (KDIGO) Hepatitis C Work Group. KDIGO 2022 Clinical Practice Guideline FOR the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease. Kidney Int. 2022 Dec;102(6S):S129-S205. doi: 10.1016/j.kint.2022.07.013. PMID: 36410841.
Patnaik R, Tsai E. Hepatitis C Virus Treatment and Solid Organ Transplantation. Gastroenterol Hepatol (N Y). 2022 Feb;18(2):85-94. PMID: 35505819; PMCID: PMC9053510.
Dao A, Cuffy M, Kaiser TE, Loethen A, Cafardi J, Luckett K, Rike AH, Cardi M, Alloway RR, Govil A, Diwan T, Sherman KE, Shah SA, Woodle ES. Use of HCV Ab+/NAT- donors in HCV naïve renal transplant recipients to expand the kidney donor pool. Clin Transplant. 2019 Jul;33(7):e13598. doi: 10.1111/ctr.13598. Epub 2019 Jun 5. PMID: 31104346.
HCV antibody positive NAT negative patient poses low risk of transmission while HCV antibody positive NAT positive donor has active infection and poses 100% risk of transmission post transplant.
Reference :
Rawashdeh B, Hulse J, et al. Transplant of a kidney from a hepatitis C viremic donor to a naive recipient without viral transmission : a case report. Am J Case Rep.2021; 22:e927532-2-e927532-4. doi: 10.12659/AJCR.927532
What is the chance of transmission of HCV in HCV antibody positive, HCV PCR negative? (1, 2)
– a positive HCV Ab and a negative HCV RNA denotes no evidence of current HCV infection hence further testing using a different HCV Ab assay helps differentiate past (resolved) infection from a false positive result
– Occult HCV infection (OCI) is defined as presence of HCV RNA in hepatocytes or peripheral blood mononuclear cells (PBMCs) with no detectable HCV RNA in the serum
– occult HCV infection can be seropositive OCI (HCV Ab positive and serum HCV RNA negative) or seronegative OCI (HCV Ab negative and serum HCV RNA negative)
– additional investigations are needed to determine the infectivity of patients with occult HCV infection
References
1. Austria A, Wu GY. Occult Hepatitis C Virus Infection: A Review. Journal of clinical and translational hepatology. 2018 Jun 28;6(2):155-60. PubMed PMID: 29951360. Pubmed Central PMCID: PMC6018308. Epub 2018/06/29. eng.
2. Castillo I, Bartolomé J, Quiroga JA, Barril G, Carreño V. Hepatitis C virus infection in the family setting of patients with occult hepatitis C. Journal of medical virology. 2009 Jul;81(7):1198-203. PubMed PMID: 19475603. Epub 2009/05/29. eng.
should be negligible,
Antibodies might persist for a longer time after clearance of the viral infection, which is indicated by negative quantitative PCR test for HCV nucleic acid.
Is it important to check urine for proteinuria and haematuria for donor who had HCV infection? Why? (1, 2)
– yes, it is important to check urine for proteinuria and hematuria
– chronic HCV infection can cause different forms of kidney disease hence the need to monitor proteinuria and hematuria
– the most common renal manifestations of HCV infection are:
Essential mixed cryoglobulinemia leading to MPGN,
MPGN without cryoglobulinemia
Membranous glomerulonephritis
– MPGN is most commonly associated with HCV infection
– other glomerulonephritides associated with HCV include:
Membranous nephropathy (MN)
Focal segmental glomerulosclerosis (FSGS)
Post infectious glomerulonephritis (PIGN)
Thrombotic microangiopathies (TMAs)
IgA nephropathy (IgAN)
References
1. Latt N, Alachkar N, Gurakar A. Hepatitis C virus and its renal manifestations: a review and update. Gastroenterology & hepatology. 2012 Jul;8(7):434-45. PubMed PMID: 23293553. Pubmed Central PMCID: PMC3533219. Epub 2013/01/08. eng.
2. Markowitz GS, Cheng JT, Colvin RB, Trebbin WM, D’Agati VD. Hepatitis C viral infection is associated with fibrillary glomerulonephritis and immunotactoid glomerulopathy. Journal of the American Society of Nephrology : JASN. 1998 Dec;9(12):2244-52. PubMed PMID: 9848778. Epub 1998/12/16. eng.
HCV seropositive, but negative HCV PCR have very low risk of transmission. In cases who both positive serology and PCR, all recipients will be infected by HCV after kidney transplantation and need treatment with DAA and monitoring.
Yes, this donor may be accepted. Since the donor has a normal renal function and he is HBsAg negative, HBsAb negative, HBcAb negative, HCV antibody is positive, but HCV PCR is negative and both HBeAg and HBeAb are negative, he has had a previous HCV infection but is now non-infective.
However, an occult HCV infection within the donated organ may flare post-transplant due to immuno-suppression. Hepatitis C testing should be done post-transplant and treatment given if positive.
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Yes, donation from HCV-infected live donor is acceptable whether HCV status of the recipient is positive or negative.
Conditions that need to be met:
Donors should receive treatment for HCV before donation if the recipient is HCV-uninfected until they achieve sustained virologic response (SVR). Treating HCV infection before transplantation can reduce the risk of HCV-associated renal dysfunction.
The assessment of renal function, urine protein and RBC to exclude HCV associated nephropathy has to be undertaken for the donor prior to deciding whether the organ can be harvested.
Assuming HCV PCR is not available, how would you manage the case?
The patient (recipient) and his/her family need to be well counseled about the possible risk of infection by HCV RNA Positive donor.
If HCV RNA by PCR of the donor is unavailable, we have to assume a positive RNA by
PCR for HCV and commence DAA prior to transplant surgery. HCV RNA by PCR needs to be checked in the post-transplant period at 7th day, 14th day and 6weeks post-transplant and DAA continued upto 12 weeks if positive.
References:
KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease VOLUME 102 | ISSUE 6S | DECEMBER 2022 http://www.kidney-international.org
I will accept this donor because his viral load is negative. With the extended pool of donations, such patients are utilized. we need to make sure about end organ damage. Regarding the kidneys, we need to make sure about proteinuria. A renal biopsy can be taken (in my opinion) to check for silent glomerular disease. For liver donation, we need to ensure the absence of cirrhosis. The longer the duration of HCV positivity, the more the risk for glomerular pathology (MPGN, Cryoglobulinemia etc. )
If this donor was a live donor, I would have time to check for eligibility. This should be discussed with the recipients and weighed: staying on dialysis with worse outcomes vs being transplanted with a higher risk of viral infections, including CMV virus
If the HCV RNA is not available (in this DBD case), I need to ensure the availability of direct antiviral therapy. Direct antiviral therapy can be started peri or post-operatively. but we need to ensure support and availability. Both THINKER and EXPANDER-1 trials showed accepted results for HCV viremic donations to HCV-negative patients.
,,,,,,,,
Pagan, Javier1; Ladino, Marco1,2; Roth, David1. Should My Patient Accept a Kidney from a Hepatitis C Virus–Infected Donor? Kidney360 1(2):p 127-129, February 2020. | DOI: 10.34067/KID.0001012019
)
Will you accept this DBD donor? Yes, I accept for donation. HCV Ab positive indicates previous infection. PCR is negative as well.
Will you accept this donor as a live donor if the recipient is HCV-positive? If yes, what are the conditions that should be met? Yes, I will accept this donor and the following conditions to be met: · Donor kidneys should not have any sign of nephropathy; renal function tests, urine analysis for RBC, albumin. · It is recommended that donors with HCV infection should receive direct anti-viral treatment (DAA) for HCV before transplantation for 12 weeks to minimize the risk of HCV transmission to HCV-negative recipients · The recipient should undergo anti-viral treatment post-transplant. · Informed consent. Assuming HCV PCR is not available, how would you manage the case?
Counseling of recipient and informed consent.
Post transplant treatment with anti-viral may necessary as there is documented favourable outcomes compared with non-viremic donors with treatment with DAA.
Reference: · Ronit Patnaik et.al. Hepatitic C Virus Treatment and Solid Organ Transplantation. Gastroenterology & Hepatology Volume 18, Issues 2, February 2022. · KDIGO 2022
· UpToDate
Yes, we can accept; (after availabilty od DAA), which helps reducing waitlisting recipients and reduce mortality while being on dialysis, and to expand donors pool
HCV Ab +ve without history of treatment, with use of DAA for 12 weeks.
HCV Ab +ve with documented SVR after treatment.
With low risk of infection. 5 and 10 years survival rates was 84.8% to 72.7% respectively, by one study HCV+ve live donor/HCV R+ve We can accept with the following
HCV NAT.
Start DAA prior to transplantation.
SVR12.
If PCR is not available
We can use NAT.
Give DAA prior to transplantation.
References
Belga S, Doucette KE. Hepatitis C in non-hepatic solid organ transplant candidates and recipients: a new horizon. World J Gastroenterol. 2016;22(4):1650-1663. 2. Kwong AJ, Kim WR, Lake JR, et al. OPTN/SRTR 2019 annual data report: liver. Am J Transplant. 2021;21(suppl 2):208-315. 3. Health Resources & Services Administration. Organ donation statistics. https:// http://www.organdonor.gov/learn/organ-donation-statistics/detailed-description#fig1. Updated October 2021. Accessed November 7, 2021.
Wolfe RA, Ashby VB, Milford EL, et al. Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N Engl J Med. 1999;341:1725-1730.
Centers for Disease Control and Prevention. Hepatitis C.
This donor is HCV Ab positive and HCV PCR negative which means either
Spontaneous clearance of infection, treated infection or false negative results.
Recipients of kidneys from HCV-Ab positive/ HCV-RNA negative donors showed the same patient and graft survival compared to recipients of HCV-Ab negative kidneys.
The recipient must be counselled before transplantation about the protentional risk of HCV infection from infected donor.
The recipient should be tested for HCV RNA within first week post-transplantation then on day 14 than at 6 weeks. If the recipient turns up positive, HCV treatment should be initiated within 3-10 days of first positive HCV RNA.
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met? Yes, I will accept this donor. Conditions to be met:
1- Donor kidneys doesn’t show nephropathy (kidney function tests, urine analysis for blood and proteins and potential biopsy). It is recommended that donors with HCV infection should receive direct anti-viral treatment (DAA) for HCV before transplantation for 8-12 weeks to minimize the risk of HCV transmission to HCV-negative recipients or super-infection with another genotype in HCV-positive recipients. SVR (Sustained Virologic Response) at 12 weeks is considered a marker of HCV cure.
2- Recipient assessment: compensated or decompensated liver cirrhosis, presence of portal hypertension, HCV genotpe. There are limited data about the safety of renal transplantation into HCV negative recipient or HCV positive with different HCV genotype from a living donor with HCV positive who undergone successful antiviral treatment. The recipient should undergo anti-viral treatment post-transplant.
3- Availability duration of the living donor for at least 24 weeks so the decision to treat before or after transplantation can be decided.
4- Willingness of both donor and recipient.
KDIGO 2018 recommended that kidneys from HCV-positive/RNA positive donor should be given only to HCV positive recipients.
Assuming HCV PCR is not available, how would you manage the case?
I will consider it as HCV positive, so the recipient should be counselled before proceeding for transplantation. The recipient should be tested for HCV RNA within first week post-transplantation then on day 14 than at 6 weeks. If the recipient turns up positive, HCV treatment should be initiated within 3-10 days of first positive HCV RNA.
· Will you accept this DBD donor? Yes, as he HCV PCR negative and risk of transmission is very low. Transmission rate of 1.9%, in the setting of a falsenegative NAT at the time of donation. Pooling available data from HCV non-viremic donors, including the single false-negative NAT case, there is an overall transmission rate of 1.1%. When donor viremia has been adequately excluded with HCV NAT testing, there have been no documented cases of transmission from non-viremic donors to HCV-naïve recipients. However the risk from viremic patients without DAA is almost 100% in HCV naïve patients. · Will you accept this donor as a live donor if the recipient is also HCV. Yes, it will be more easier provided that it is same genotype or genotype group. · Assuming HCV PCR is not available, how would you manage the case? It will be difficult to take decision in such situation. However if the recipient is in need for urgent transplantation, I may consider it after explanation of the risk of transmission and the unavailable data. References: 1-Expanding the Deceased Donor Pool in Manitoba Using Hepatitis C-Viremic Donors: Program Report, Canadian Journal of Kidney Health and Disease Volume 8: 1–10
Will you accept this DBD donor?
Yes, I would accept this donor. HCV Ab + with NAT -ve (not viremic) indicated that virus clearance spontaneously or with treatments (no active infection).In other words, is no current hepatitis C (1). However, this could be due to false positive results. Overall the transmission risk is very low (2)
Will you accept this donor as a live donor if the recipient is HCV-positive? If yes, what are the conditions that should be met?
Yes, provided there is access to DAA therapy post-transplantation, and the donor has no evidence of cirrhotic liver.
Assuming HCV PCR is not available, how would you manage the case?
Councell the patients (recipient) and take high-risk consent (3).
Treat as Hep C positive donor (viremic)
Start treatment peri-operatively
Documented favourable outcomes compared with non-viremic donors with treatment with DAA.
Reference
An update of guidance for clinicians and laboratorians. MMWR 2013;62(18).
Ronit Patnaik et.al. Hepatitic C Virus Treatment and Solid Organ Transplantation. Gastroenterology & Hepatology Volume 18, Issues 2, February 2022.
Thank you All. I’ve noticed a few of you who referred to the recently published KDIGO guidelines for hepatitis C in CKD.
It states the following:
‘ 4.2.3: We recommend that kidneys from HCVinfected donors be considered regardless of HCV status of potential kidney transplant recipients (1C).
The most important points here are: 1- Recipient counselling, discussions, education for an informed consent 2- Recipient should be treated promptly after transplantation for 12 weeks with excellent patient and graft survival and excellent SVR12.
Clearly in our scenario treatment post transplant is not mandatory as donor was HCV antibody only positive
My approach in this case would probably wait for HCV PCR result which will confirm donor infectivity and to know the gene type of the virus and if this is negative no need for treatment with a recheck of HCV after 12 weeks post transplantation to ensure no risk of viral transmission.
In the unlikely event of difficulty getting HCV PCR result for any reason, then will use DAA empirically for 12 weeks with lack of virus genotype with risk of suboptimal treatment response.
In this scenario given, HCV PCR results are not available (HCV Ab positive) upon transplantation, we proceed with transplantation (after counselling the risk and benefit) and trace back the NAT and the genotype retrospectively before initiating treatment?
👉 Yes I will accept this donor (postive anti HCV Antibody and negative PCR), as this means clearance from infection either spontaneously or with treatment 👉 although the risk of transmission in the index case is very low, Follow up of the recipient by PCR is essential to detect presence of any viremia (if tested positive at any time, early treatment is indicated with GZR/EBR for 12 weeks till achieving SVR.
👉 If the is alive donor, I can accept the donor for HCV postive recipient (with the following precautions)
⭐ After making sure that no evidence of HCV associated nephropathy (cryoglobulinemia, MN or MPGN) as this can be associated with recurrent or Denovo disease in the allograft (urinalysis showing hematuria/protinuria).
⭐ The donor has no advanced cirrhosis by liver biopsy, ultrasound and fibroscan).
⭐ The recipient has no evidence of advanced cirrhosis that can require combined liver and kidney transplant ion.
⭐ Treatment of both the donor and the recipient either pretransplant (if no urgency for transplantation now) or starting after transplantation.
👉 If no available PCR, deal with the donor as HCV postive with counseling of the recipient about the risk of viremia post transplant, the need for frequent PCR monitoring and starting early ttt once postive PCR.
Ø Hepatitis C Ab+ donors should be defined by NAT testing as non-viremic (NAT−) versus viremic (NAT+) Hepatitis C Ab+/NAT− kidneys can be transplanted safely into HCV− recipients
Ø Post-transplant NAT testing is recommended to confirm lack of disease
Ø HCV− recipients transmission; if de novo HCV infection occurs, DAAs should be rapidly instituted
Ø Hepatitis C Ab+/NAT− kidneys can be transplanted into HCV NAT+ recipients,DAA treatment should begin post-transplant
Ø Transplantation with HCV NAT+ kidneys into HCV NAT+ recipients is recommended
Ø Post-transplant DAA treatment should be started
Transplantation with HCV NAT+ kidneys into HCV− recipients with DAA treatment is possible
Ø KDIGO : HCV− recipients of HCV NAT+ organs should be followed closely to capture potential complications
References :
1. Kidney Disease Improving Global Outcomes KDIGO clinical practice guidelines for the prevention, diagnosis, evaluation and treatment of hepatitis c in chronic kidney disease. Kidney Int 2008; 73(suppl 109): S1–S99.
2. Sawinski D, Bloom RD. Novel hepatitis C treatment and the impact on kidney transplantation. Transplantation. 2015:1–9.
3- Fabrizi F, Cerutti R, Alfieri CM, Mesa P. Updated view on kidney transplant from HCV-infected donors and DAAs. Pharmaceutics. 2021;13:496.
· Positive anti-HCV antibody may reflect neutralization and immunity after clearance of previous HCV infection.
· It is well recommended by KDIGO that all kidney transplant candidates with HCV be considered for DAA therapy, either before or after transplantation (1).
· It is recommended by KDIGO that kidneys from HCV-infected donors be considered regardless of HCV status of potential kidney transplant recipients (1).
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Yes, I will accept: donation from HCV-infected donor is acceptable and have to be considered regardless of HCV status of the KTR as stated by KDIGO guidelines.
Conditions that should be met are:
1. Donors do not have cirrhosis.
2. Donors should undergo HCV treatment before donation if the recipient is HCV-uninfected; they can be accepted for donation if they achieve sustained virologic response (SVR) and remain otherwise eligible to be a donor(1).
Assuming HCV PCR is not available, how would you manage the case?
In the setting of unavailability of HCV PCR, I will consider the donor positive PCR for HCV. In such situation, I will initiate DAAs in the early post-transplant period. HCV PCR to be checked in the post-transplant period at day3-day7 – day10 -day14 and 6weeks post-transplant.
· Transplantation of HCV-viremic organs into HCV-naive recipients followed by the use of DAA agents provides excellent patient and allograft survival(2).
· Securing DAA therapy post-transplant is essential and patients should be fully informed of the associated risks, including the potential of HCV treatment failure(2). References 1. KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease VOLUME 102 | ISSUE 6S | DECEMBER 2022 http://www.kidney-international.org 2. Patnaik R, Tsai E. Hepatitis C Virus Treatment and Solid Organ Transplantation. Gastroenterol Hepatol (N Y). 2022 Feb;18(2):85-94. PMID: 35505819; PMCID: PMC9053510.
Yes . This deceased donor has either treated or cleared HCV infection; there is low risk of transmission so I will proceed for transplantation .
Will you accept this donor as a live donor if the recipient is also HCV
? positive .If yes, what are the conditions that should be met .
Yes ,kidney transplantation is the best therapeutic option for patients with CKD G5 irrespective of HCV infection status
For positive living donors :
The donor should be tested for HCV PCR if positive he is for genotyping and evaluation regarding presence of chronic liver disease as well as renal involvement by check of presence of hematuria and or proteinuria and should be managed with suitable DAA.
For the recipient :
Possible kidney transplant candidates who have anti-HCV antibody–positive require confirmation of viremia (HCV RNA), and evaluation of the severity of liver disease and extent of fibrosis, If they have any evidence of decompensated cirrhosis or significant portal hypertension they should be evaluated for simultaneous liver–kidney transplant even if they have achieved SVR, but if has compensated liver disease without portal HTN we can proceed to kidney transplantation as progression of liver disease can be controlled with DAA.
?Assuming HCV PCR is not available, how would you manage the case
– Regarding the recipient who has positive HCV Ab and no PCR available we should assess his liver function test and liver enzymes other viral screening besides liver US and fibroscan for signs of fibrosis,if there is significant fibrosis with portal HTN he is for simultaneous liver and kidney transplantation if not to proceed for kidney transplantation with follow up of viral load and treatment with DAA if detected HCV RNA .
– Regarding the deceased donor I will proceed , if living donor with HCV Ab positive and no PCR , assessment of liver function and imaging for signs of chronicity plus evaluation for possible renal involvement by urine analysis for RBC and urine PCR and manage accordingly .
: Reference
Kidney Int. 2022 Dec;102(6):1228-1237. doi: 10.1016/j.kint.2022.07.012.
Executive Summary of the KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease
Will you accept this DBD donor? Yes. In this HCV antibody is positive but HCV PCR is negative. HCV positive antibody and negative PCR can be due to previous treatment, spontaneous clearance ,false positivity or low viral load, . There is no contraindication for donation.
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met? Yes I will accept . Criteria for HCV positive donation to HCV Positive recipient include- Absent cirrhosis and HCC in both Rule out CKD in donor Available DAA for both donor and recipient Informed consent Negative PCR Treatment of donor pre donation with sustained virologic response Planned follow up
Assuming HCV PCR is not available, how would you manage the case? I will proceed with transplantation but will monitor him post transplant. If he becomes HCV positive then I will start direct antiviral therapy.
Patnaik R, Tsai E. Hepatitis C Virus Treatment and Solid Organ Transplantation. Gastroenterol Hepatol (N Y). 2022 Feb;18(2):85-94.
Will you accept this DBD donor?
Yes HCV Ab positive and HCV RNA negative indicates absence of active HCV infection
Additional tests to determine whether the initial positive HCV antibody represents clearance of a previous infection or a false‐positive test result can be considered, repeat HCV antibody testing using an approved HCV antibody assay
In this case the risk is small of HCV being transmitted to the recipient.
Meanwhile the DAAs presence curing HCV infection after transplant increased the acceptance of HCV+ kidneys also due to survival benefit associated with transplantation than remaining on the waiting list.
Standardized testing for HCV RNA of the recipient after receiving a HCV Ab positive graft to attain an early and appropriate intervention if HCV transmission and infection occurs.
f HCV PCR is positive after confirmatory results DAA to be started within 3-10 working days since the first positive test.
There are 2 regimens including combination of Glecaprevir/Pibrenatasvir or the combination of Sofosbuvir/Velpatasvir, both given for 12 weeks Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Yes, pending full evaluation of the severity of their liver disease of donor and recipient. NAT to confirm SVR durability in cases in patients who received antiviral treatment prior to waitlisting and obtaining SVR. Assuming HCV PCR is not available, how would you manage the case?
Enzyme immunoassay can be done if NAT is not available
Short course of DAAT regimen can be given and SVR assessed Reference –Bowring MG, Kucirka LM, Massie AB, et al. Changes in Utilization and Discard of HCV Antibody-Positive Deceased Donor Kidneys in the Era of Direct-Acting Antiviral Therapy. Transplantation. 2018;102(12):2088-2095.
-Summa KC, Maddur H. Hepatitis C Antibody Positive, RNA Negative. Clin Liver Dis (Hoboken). 2019;14(1):5-7. Published 2019 Aug 2.
– Kidney Disease: Improving Global Outcomes. KDIGO clinical practice guidelines for the
prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease.
Kidney Int. 2008; 73 (suppl 109):S1–S99
56 ys old DBD, SAH, normal s.cr on retrieval, HIV, HBsAg -ve, HCV ab positive with negative PCR.
Will you accept this DBD donor?
Yes, I will. No contraindications.
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Yes, I will.
– Causes of HCV ab positive with PCR negative:
1- Infection with Low undetected viral load.
2- Treated infection.
3- No infection; False positive test, recent blood transfusion with anti-HCV positive ab.
– So, the status here will be either HCV-infected donor to HCV-infected recipient or HCV-non-infected donor to HCV-infected recipient, in both conditions, I will accept as a live donor.
– MDT management with a hepatologist to asses:
1- Need for simultaneous liver & kidney transplant if decompensated liver D or portal HTN>10 mmHg.
2- Option of pre-transplant treatment, otherwise could be treated post-transplant.
Assuming HCV PCR is not available, how would you manage the case?
– NAT is more sensitive & specific in detecting if sensitivity or viremia, to classify the risk of transmission, but if also not available, I will consider him as HCV infected. – So, if the recipient also is HCV positive, will proceed for transplantation with post-transplant treatment with DAA. – If the recipient is negative, will proceed for transplantation if no available HCV-negative donors, or need for urgent transplantation like vascular access failure or a long time on the waiting list with informing & consenting the recipient. – THINKER trial shows good outcomes in transplanting HCV -ve donors from HCV +ve. – AS PER BTS recommendations:
– Recipient will be tested for PCR HCV on day 3- 7 & If negative The test is repeated in day 10-14 post-transplantation & If negative again The test is repeated in 6 weeks post-transplant .
– DAA started 3 to 10 days after any positive result of PCR HCV
Will you accept this DBD donor?
Yes I will accept this donor
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Yes I will accept this as donor after fulfiling following conditions.
Assess viral load of the recipient
If possible start DAA in recipient to clear viral load before moving ahead for transplant
Assuming HCV PCR is not available, how would you manage the case?
I will go ahead for transplantation but will start DAA as per the post transplant regeimn protocol, giving benefit to recipient and considering that DBD donor might be having some viral load.
Yes, I will accept with availability of DAA and comprehensive informed consent
This is a seropositive, nonviremic HCV infection and the risk of disease transmission is low. Possibilities of HCV Antibody+/HCV NAT- are:
1. spontaneous clearance of HCV
2. successful treatment of infection
3. false-positive antibody result
Anti-HCV antibody+/HCV RNA – should be tested for HCV RNA 12 and 24 weeks latter to confirm defitive clearance
KDIGO 2022: we recommend that kidneys from HCV-infected donor be considered regardless of HCV status of potential kidney transplant recipients (1C).
Recipient HCV PCR day 3-7, day 10-14, and 6 weeks post-transplant. If positive at any time start DAA therapy within 3-10 days of the first positive test after confirmatory test
Securing DAA therapy post-transplant is essential and patients should be fully informed of the associated risks, including the potential of HCV treatment failure
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Yes, I will accept
KDIGO 2022: we recommend kidney transplantation as the best therapeutic option for patients with CKD-G5 irrespective of presence of HCV infection (1A)
Management of the recipient: Evaluate for severity of liver disease and presence of portal hypertension:
1. Compensated cirrhosis and no portal hypertension: isolated kidney transplantation
2. Decompensated cirrhosis or clinically significant portal hypertension (hepatic venous gradient pressure 10 or more or evidence of portal hypertension on imaging or exam): simultaneous liver kidney transplantation
3. Mild to moderate portal hypertension treatment should be determined on a case-by-case basis
Timing of HCV treatment in relation to kidney transplantation (before vs. after):
Generally based on
1. donor type (living vs. deceased)
2. wait-list times by donor types
3. center-specific policies governing the use of kidneys from HCV-infected deceased donors
4. severity of liver cirrhosis
5. candidate sensitization
6. patient preference
All kidney transplant candidates with HCV be considered for DDA therapy, either before or after transplantation (1A)
HCV-infected kidney transplant candidates with a living kidney donor be considered for treatment before or shortly after transplantation depending on the anticipated timing of transplantation (2B).
Maintenance of immunosuppressions:
Evaluate for the need for dose adjustment of immunosppressants in kidney transplant recipient treated with DAA For F0 to compensated cirrhosis without portal hypertension:
o If living donor kidney transplantation is anticipated without a long wait (<24 weeks), treatment can be deferred until after transplantation (avoid drug-drug interaction peritransplant)
o If living donor kidney transplantation is likely to be delayed more than 24 weeks, HCV therapy can can be offered before or after transplantation (12 weeks for therapy and 12 weeks of follow-up to confirm SVR)
Combinations DAA used in post-transplant settings include glecaprevir-pibrentasvir, sofosbuvir-ledipasvir, sofosbuvirsimeprevir, sofosbuvir-daclatasvir and paritaprevirdasabuvir
Few DAA such as simeprevir and dasabuvir are associated with significant drug interaction with immunosuppressants. Close monitoring of the therapeutic drug level of calcineurin inhibitor is required with use of DAA in SOT
Correct factors associated with accelerated disease including alcohol use, obesity, insulin resistance and substance abuse
Hepatitis c infection after transplantation is associated:
1. liver disease
2. Recurrence or new onset of HCV related kidney disease (recurrent glomerular disease or de novo MPGN or MN, renal thrombotic microangiopathy). As HCV associated glomerular disease usually presents with progressive proteinuria, screen regularly for proteinuria and haematuria (every 6 months)
3. PTLD
4. NODAT
5. fibrosing cholestatic hepatitis: rare and characterized by cholestasis and progressive liver failure HCV associated kidney disease after transplant include
Assuming HCV PCR is not available, how would you manage the case?
HCV core antigen in serum or plasma is a marker of HCV replication and can be used instead of HCV RNA to diagnose acute or chronic HCV infection when HCV RNA is not available and/or not affordable
If both are not available, I will consider HCV RNA positive and proceed for transplantation
References
1. Kidney Disease: Improving Global Outcomes (KDIGO) Hepatitis C Work Group. KDIGO 202 2 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in ChronicKidney Disease. Kidney Int. 2022;102(6S):S129–S205.
2. Pantnaik R, Tsai E, Hepatitis C Virus Treatment and Solid Organ Transplantation. Gastroenterol Hepatol (NY). 2022 Feb;18(2):85-94. PMID:35505819; PMCID: PMC9053510.
3. UK Position Statement on the use of Organs from Hepatitis C Viraemic Donors and Increased Infectious Risk Donors in Hepatitis C Negative Recipients.
4. Sawinski D, et al. Renal transplantation using kidneys from hepatitis C-infected donors: A review of 30-years’ experience. Nefrologia. 2022.https://doi.org/10.1016/j.nefro.2022.04.005
5. Shenoy P, Buttigieg J, Zayan T, Sharma A & Halawa A. (2018) Infections after Solid Organ Transplantation. J Renal Transplant Sci, 1(1): 29-42.
6. EASL Recommendations on Treatment on Hepatitis C 2018.
The index patient is offered a kidney from a 56-year-old male DBD (donor after brainstem death) kidney with no evidence of Hepatitis B and HIV infection, and presence of anti-HCV antibodies and absent HCV RNA PCR.
The scenario implies either a false positive anti-HCV antibody, or a past infection which either got cleared spontaneously (in 5% cases), or after being treated.
The HCV status of the recipient has not been provided. Nevertheless, I will accept this donor in view of low-risk of transmission in absence of viremia, after counselling the recipient and HCV positive donors can be accepted regardless of the HCV status of the potential kidney transplant recipient (1).
Post-transplant, the recipient should be tested for HCV RNA PCR (2). The testing should be done on day 3-7, then on day 10-14, and then 6 weeks post-transplant. If the reports are negative even at 6 weeks, the recipient can be reassured. If the HCV PCR comes out positive during the testing in first 6 weeks, the patient should be treated with directly acting antivirals (DAAs) within 3-10 days (2).
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
In the scenario of a live donor who is anti-HCV antibody positive, donating to a recipient who is HCV positive, I will accept the donor after evaluating both the donor and the recipient. HCV positive donors can be accepted regardless of the HCV status of the potential kidney transplant recipient (1).
Recipient evaluation: The recipient should be evaluated with respect to positive HCV status – anti-HCV antibodies, HCV RNA PCR, hepatology consultation, Liver function tests, ultrasound abdomen, and assessment of liver fibrosis (elastography, liver biopsy) and portal hypertension (upper gastrointestinal endoscopy). In presence of advanced liver fibrosis, a combined liver and kidney transplant would be required.
Donor evaluation: The prospective donor should be evaluated with HCV nucleic acid testing (HCV-NAT), which if positive, would require hepatology consultation and evaluation of liver disease in form of liver function tests (LFT). The prospective donor should also be monitored for renal function, hematuria, and proteinuria (1).
The prospective living donor should be treated with DAA therapy. Living donation can be proceeded with in absence of severe hepatic fibrosis and renal disease. In case both the donor and recipient are HCV infected, the DAA treatment of the donor can be delayed (1). If the recipient is HCV-uninfected, then the donor should be treated pre-donation (1).
In the index scenario, as the live donor is HCV RNA PCR negative, no need of DAA treatment for the donor. If there is no hepatic or renal dysfunction, the donor can be accepted. As the recipient is HCV positive, the recipient evaluation should be done as enumerated above. If recipient HCV RNA PCR is positive, the recipient should be treated with DAAS. If there is urgency (poor vascular access, patient not tolerating dialysis), then the transplant can be proceeded with and the treatment of the recipient can be done post-transplant.
Assuming HCV PCR is not available, how would you manage the case?
If the donor HCV PCR is not available, the transplant can be proceeded with. Post-transplant, the recipient should be tested for HCV RNA PCR (2). The testing should be done on day 3-7, then on day 10-14, and then 6 weeks post-transplant. If the reports are negative even at 6 weeks, the recipient can be reassured. If the HCV PCR comes out positive during the testing in first 6 weeks, the patient should be treated with directly acting antivirals (DAAs) within 3-10 days (2).
References:
Kidney Disease: Improving Global Outcomes (KDIGO) Hepatitis C Work Group. KDIGO 2022 Clinical Practice Guideline FOR the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease. Kidney Int. 2022 Dec;102(6S):S129-S205. doi: 10.1016/j.kint.2022.07.013. PMID: 36410841.
Martin P, Awan AA, Berenguer MC, Bruchfeld A, Fabrizi F, Goldberg DS, Jia J, Kamar N, Mohamed R, Pessôa MG, Pol S, Sise ME, Balk EM, Gordon CE, Adam G, Cheung M, Earley A, Jadoul M. Executive Summary of the KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease. Kidney Int. 2022 Dec;102(6):1228-1237. doi: 10.1016/j.kint.2022.07.012. PMID: 36411019.
Potential donor has isolated HCV positive by serologic testing but NAT negative (nonviremic), which may result of the following:
– Spontaneous clearance or successful treatment of infection.
– False-positive antibody result.
– Recent blood transfusion with anti-HCV. ( antibodies will disappear over thenext few weeks in keeping with T1/2 of IgG)
– Vertical transmission in neonate.
– False-negative RNA test, unusual very low viral load.
Therefore, this donor can be accepted. As these donors have not been documented to transmit HCV infection, and outcome is good. Recipients of HCV-seropositive/RNA-negative kidneys appear to have the same graft and patient survival as recipients of HCV-seronegative kidneys (1) However, this recipient should be monitored with HCV PCR at day 3-7 Post-Tx, then day 10-14,then at 6 weeks if all results are negative reassure the recipient & managed as standard recipients. If HCV PCR positive; DAA started within 3-10 days of first positive PCR.
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Yes This donor can be accepted in the setting of LD, after careful evaluation, as the use of HCV RNA positive organs with early initiation of DAA is recently being acceptable.
Transplantation should be avoided in recipients with advanced fibrosis or cirrhosis.
Evaluation include:
– Liver function test.
– Liver US.
– Screening using AST-to-Platelet Ratio Index (APRI).
If the APRI score is >0.8 or the ultrasound suggests significant or advanced liver disease, then liver specialist opinion is recommended.
If the APRI score is <0.8, there is no need for the patient to be seen by a liver specialist.
– Liver biopsy may be required.
-Evaluate for extrahepatic manifestation: renal involvement with:
-Renal function.
-Urine analysis for proteinuria, hematuria.
Consider treatment for LD before transplantation if no urgent transplantation and after balancing risk and benefit.
Recipient with HCV PCR positive:
Evaluated the same way
If found to have advanced liver disease may benefit from combined liver-kidney transplantation.
Consider treating the recipient ( while waiting on the list) before transplantation to avoid drug-drug interaction if situation allows, and no urgent need for transplantation and donor will remain available after treatment course.
Assuming HCV PCR is not available, how would you manage the case?
We can proceed with transplantation if PCR is not available, it is saver to consider this donor as viremic with high transmission risk. Thus require frequent monitoring to ensure appropriate and early intervention if HCV transmission and infection occurs.
Testing donor HCV genotype.
Ensure the availability of HCV treatment. Recipient monitored with HCV PCR at day 3-7 Post-Tx, then day 10-14,then at 6 weeks if all results are negative reassure the recipient & managed as standard recipients.
If recipient HCV PCR positive; DAA started within 3-10 days of first positive PCR.
However, we need to balance the benefit of transplantation and donor derived infection must be considered against the risk of not receiving the organ, continuing on dialysis, waitlist time and immunological risk. References : Fontaine H, Alric L, Labreuche J, Legendre B, Louvet A, Antoine C, Legendre CM, Hazzan M, Kamar N, Dharancy S, Pol S, Duhamel A, Mathurin P. Control of replication of hepatitis B and C virus improves patient and graft survival in kidney transplantation. J Hepatol. 2019 May;70(5):831-838. doi: 10.1016/j.jhep.2018.12.036. Epub 2019 Mar 14. PMID: 30879789.
Doherty DT, Athwal V, Moinuddin Z, et al. Kidney Transplantation From Hepatitis-C Viraemic Donors:Considerations for Practice in the United Kingdom. Transpl Int. 2022;35:10277. Published 2022 May 3. doi:10.3389/ti.2022.10277
The British Viral Hepatitis Group has recently issued a position statement on the use of organs from hepatitis C viraemic donors in hepatitis C negative recipients.
Cadveric donors with heptitis C befor the great innovation of direct DDA was discarded by most of centres world wide .
After the new era of complete cure of hep C by DDA drugs most centers now accepting these kidnies .
In this index case with negtive hepaitis E ,hepatitis B,and HIV , and positive HCV antibody , i will accept the offer , and i will give the recipent mavyret (gelcaprevir/pibrentacivir) for three month as it is pangentotpic and also as hepatitis B is negative. assuming that the donor is hepatitis C positive with no avialbity of heptitis C PCR.
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Donor evalution should be done befor donating the kidney.with PCR, and offerd tretment also .
Yes Iwill accept this donor as HCV+ to HCV+ Kidney .
candidates who are HCV RNA+ should undergo liver biopsy to exclude fibrosis and the need for simultaneous liver-kidney transplantation
If they are not cirrhotic fibrosis from(0-3), patients with living donors should be treated with DAAs pre-transplantation and proceed with transplantation.
yes it is important to exculde heptistis c associated nephropathy in the form of cryoglublinemia and other GN assiocated nephropathy like MPGN , membranous nephropathy, FSGS.
It is important to rule out renal involvement that can be associated with HCV. That can be present with proteinuria, microscopic hematuria, hypertension, acute nephritis and nephrotic syndrome Common glomerular lesions including: MPGN, Mixed cryoglobulinemia, Membranous nephropathy, PAN.
Crescentic glomerulonephritis may be superimposed on any of these glomerular lesions.
Less commonly glomerular lesions: FSGS, proliferative glomerulonephritis, and fibrillary and immunotactoid glomerulopathies.
Reference: Ozkok A, Yildiz A. Hepatitis C virus associated glomerulopathies. World J Gastroenterol. 2014 Jun 28;20(24):7544-54. doi: 10.3748/wjg.v20.i24.7544. PMID: 24976695; PMCID: PMC4069286.
Johnson RJ, Willson R, Yamabe H, Couser W, Alpers CE, Wener MH, Davis C, Gretch DR. Renal manifestations of hepatitis C virus infection. Kidney Int. 1994 Nov;46(5):1255-63. doi: 10.1038/ki.1994.393. PMID: 7853784.
Thank you prof.
HCV infection after transplantation is associated with recurrent or new onset HCV related kidney disease (recurrent glomerular disease or de novo MPGN or MN, renal thrombotic microangiopathy). As HCV associated glomerular disease usually present with progressive proteinuria, sceen regularly for proteinuria and haematuria.
Reference
1. Shenoy P, et al. (2018) Infections After Solid Organ Transplantation. J Renal Transplant Sci, 1(1): 29-42.
Have you read the question carefully? It’s about the donor urine analysis to check suitability to donate a kidney in the context of previous history of HCV?
Yes as chronic HCV infection can be associated with many glomerular diseases including mixed cryoglobulinemia with MPGN-like nephropathy and membranous nephropathy, Ig A nephropathy, and FSGS as well and chronic hepatitis screen is part of proteinuria in general and in HCV related need to send C3, C4 urine p/c ratio, and cryoglobulin level and kidney biopsy
HCV associated nephropathies should be excluded or diagnosed if present like mixed cryoglobulinemia, systemic vasculitis, MPGN, MGN, FSGS,fibrillary GN
Yes .Because of cryoglobulinemia is an extrahepatic presentation of HCV infection with a histological pattern of membranoproliferative glomerulonephritis. Less frequent glomerulopathy include membranous nephropathy, focal segmental glomerulosclerosis, IgA nephropathy, fibrillary and immunotactoid glomerulopathy. Reference
Angeletti A, Cantarelli C and Cravedi P (2019) HCV-Associated Nephropathies in the Era of Direct Acting Antiviral Agents. Front. Med. 6:20
Hepatitis C virus (HCV) infection is a systemic disorder which is often associated with a number of extrahepatic manifestations including glomerulopathies. Patients with HCV infection were found to have a higher risk of end-stage renal disease. HCV positivity has also been linked to lower graft and patient survivals after kidney transplantation. Various histological types of renal diseases are reported in association with HCV infection including membranoproliferative glomerulonephritis (MPGN), membranous nephropathy, focal segmental glomerulosclerosis, fibrillary glomerulonephritis, immunotactoid glomerulopathy, IgA nephropathy, renal thrombotic microangiopathy, vasculitic renal involvement and interstitial nephritis. The most common type of HCV associated glomerulopathy is type I MPGN associated with type II mixed cryoglobulinemia. Clinically, typical renal manifestations in HCV-infected patients include proteinuria, microscopic hematuria, hypertension, acute nephritis and nephrotic syndrome. Three approaches may be suggested for the treatment of HCV-associated glomerulopathies and cryoglobulinemic renal disease: (1) antiviral therapy to prevent the further direct damage of HCV on kidneys and synthesis of immune-complexes; (2) B-cell depletion therapy to prevent formation of immune-complexes and cryoglobulins; and (3) nonspecific immunosuppressive therapy targeting inflammatory cells to prevent the synthesis of immune-complexes and to treat cryoglobulin associated vasculitis. In patients with moderate proteinuria and stable renal functions, anti-HCV therapy is advised to be started as pegylated interferon-α plus ribavirin. However in patients with nephrotic-range proteinuria and/or progressive kidney injury and other serious extra-renal manifestations, immunosuppressive therapy with cyclophosphamide, rituximab, steroid pulses and plasmapheresis should be administrated(1).
Reference
1. Ozkok A, Yildiz A. Hepatitis C virus associated glomerulopathies. World J Gastroenterol. 2014 Jun 28;20(24):7544-54. doi: 10.3748/wjg.v20.i24.7544. PMID: 24976695; PMCID: PMC4069286.
Is it important to check urine for proteinuria and haematuria for donor who had HCV infection? Why?
Dear Dr Ahmed,
The answer is yes; chronic viral infection is associated with a higher risk of developing variable forms of glomerular kidney disease (e.g. MPGN, Cryoglobulinemia and other forms of glomerulonephritis), as illustrated in the attached table (1).
References:
1) Steddon S, Ashman N, Chesser A, et al. Oxford Handbook of Nephrology and Hypertension. Second edition, Oxford University Press, ISBN 978–0–19–965161–0, 2014.
_Yes, to exclude HCV associated glomerular diseases as (cryoglobulinemia, membranous nephropathy and MPGN) that can be presented with microscopic hematuria, variable degrees of protinuria, nephritis or even nephrotic syndrome.
in addition, blood pressure monitoring is important.
Hepatitis C virus (HCV) infection is a systemic disorder associated with a number of extrahepatic manifestations including glomerulopathies
Histological types of renal diseases are association with HCV infection including : Membranoproliferative glomerulonephritis (MPGN), Membranous nephropathy Focal segmental glomerulosclerosis Fibrillary glomerulonephritis, Immunotactoid glomerulopathy IgA nephropathy, Renal thrombotic microangiopathy, Vasculitic renal involvement Interstitial nephritis.
The most common type of HCV associated glomerulopathy is type I MPGN associated with type II mixed cryoglobulinemia
Clinically, in HCV-infected patients include proteinuria, microscopic hematuria, hypertension, acute nephritis and nephrotic syndrome The treatment of HCV-associated glomerulopathies and cryoglobulinemic renal disease: (1) antiviral therapy to prevent the further direct damage of HCV on kidneys and synthesis of immune-complexes; (2) B-cell depletion therapy to prevent formation of immune-complexes and cryoglobulins. (3) nonspecific immunosuppressive therapy targeting inflammatory cells to prevent the synthesis of immune-complexes and to treat cryoglobulin associated vasculitis serious extra-renal manifestations, immunosuppressive therapy with cyclophosphamide, rituximab, steroid pulses and plasmapheresis should be administrated. REFERNCE: 1. Cacoub P, Renou C, Rosenthal E, Cohen P, Loury I, Loustaud-Ratti V, Yamamoto AM, Camproux AC, Hausfater P, Musset L, et al. Extrahepatic manifestations associated with hepatitis C virus infection. A prospective multicenter study of 321 patients. The GERMIVIC. Groupe d’Etude et de Recherche en Medecine Interne et Maladies Infectieuses sur le Virus de l’Hepatite C. Medicine (Baltimore) 2000;79:47–56. [PubMed] [Google Scholar]
Is it important to check urine for proteinuria and haematuria for donor who had HCV infection? Why?
Yes. It is important to have a urine analysis of the prospective donor to look for hematuria/ proteinuria to rule out any glomerular disease which could be HCV related or unrelated to HCV infection. These include cryoglobulinemic MPGN, membranous nephropathy, or FSGS (1).
Reference:
Kidney Disease: Improving Global Outcomes (KDIGO) Hepatitis C Work Group. KDIGO 2022 Clinical Practice Guideline FOR the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease. Kidney Int. 2022 Dec;102(6S):S129-S205. doi: 10.1016/j.kint.2022.07.013. PMID: 36410841.
Thanks, our Prof,
Yes, it is important to check urine for the donor with HCV + infection
because the effect of HCV on kidney in the form of;
MPGN, Cryoglobulinemia ,FSGS, IgAN , Membranous nephropathy ,Fibrillary GN , Immunotactoid GN , Diabetic nephropathy.
Yes it is important to check urine for proteinuria and hematuria. This is because patient with HCV infection are at risk of developing some glomerulonephrits like: 1-Cryoglobuinemia, MPGN type 1. 2-Membranous nephropathy. 3-FSGS 4-Ig A nephropathy 5-Immunotactoid glomerulopathy 6-Interstitial nephritis 7-TMA 8-Renal vasculitis References: World Journal of gastro entrology 2014, 28; 20(24) 7544-7554
Yes, to exclude underlying GN membranoproliferative glomerulonephritis (MPGN), membranous nephropathy, focal segmental glomerulosclerosis, fibrillary glomerulonephritis, immunotactoid glomerulopathy, IgA nephropathy, renal thrombotic microangiopathy, vasculitic renal involvement,, and interstitial nephritis. The most common type of HCV-associated glomerulopathy is a type I MPGN associated with type II mixed cryoglobulinemia. Clinically, typical renal manifestations in HCV-infected patients include proteinuria, microscopic hematuria, hypertension, acute nephritis, and nephrotic syndrome.
Renal manifestations in HCV-infected patients include proteinuria, microscopic hematuria, hypertension and nephrotic syndrome. Often patients have impaired renal fuction. The most common type of HCV associated glomerulopathy is MPGN associated with type II mixed cryoglobulinemia.
Other histological types of renal diseases reported in association with HCV infection include:
membranoproliferative glomerulonephritis (MPGN),
membranous nephropathy,
focal segmental glomerulosclerosis,
fibrillary glomerulonephritis,
IgA nephropathy,
thrombotic microangiopathy,
Reference:
Habas E Sr, Farfar KL, Errayes N, Habas AM, Errayes M, Alfitori G, Rayani A, Elgara M, Al Adab AH, Elzouki A. Hepatitis Virus C-associated Nephropathy: A Review and Update. Cureus. 2022 Jul 27;14(7):e27322. doi: 10.7759/cureus.27322. PMID: 36043014; PMCID: PMC9412079.
To check for cryoglobulinemia since this is a typical extra hepatic manifestation of HCV infection. Cryoglobulinemia involves the kidneys and has a histological pattern of membranous glomerulonephritis.
Other less common renal diseases linked to HCV infection include membranous nephropathy, focal segmental glomerulosclerosis, IgA nephropathy, fibrillary and immunotactoid glomerulopathy.
Typically, clinical manifestations include proteinuria, microscopic hematuria, hypertension, acute nephritis and nephrotic syndrome.
References :
Angeletti A, Canterelli C, Cravedi P. HCV associated nephropathies in the era of direct acting antiviral agents. Front Med. 2019;6. https://doi.org/10.3389/fmed.2019.00020
Ozkok A, Yildiz A. Hepatitis C virus associated glomerulopathies. World J Gastroenterol. 2014; 20(24) : 7544-7554. PMCID: PMC4069286 PMID: 24976695
Is it important to check urine for proteinuria and haematuria for donor who had HCV infection? Why? (1, 2)
– yes, it is important to check urine for proteinuria and hematuria
– chronic HCV infection can cause different forms of kidney disease hence the need to monitor proteinuria and hematuria
– the most common renal manifestations of HCV infection are:
Essential mixed cryoglobulinemia leading to MPGN,
MPGN without cryoglobulinemia
Membranous glomerulonephritis
– MPGN is most commonly associated with HCV infection
– other glomerulonephritides associated with HCV include:
Membranous nephropathy (MN)
Focal segmental glomerulosclerosis (FSGS)
Post infectious glomerulonephritis (PIGN)
Thrombotic microangiopathies (TMAs)
IgA nephropathy (IgAN)
References
1. Latt N, Alachkar N, Gurakar A. Hepatitis C virus and its renal manifestations: a review and update. Gastroenterology & hepatology. 2012 Jul;8(7):434-45. PubMed PMID: 23293553. Pubmed Central PMCID: PMC3533219. Epub 2013/01/08. eng.
2. Markowitz GS, Cheng JT, Colvin RB, Trebbin WM, D’Agati VD. Hepatitis C viral infection is associated with fibrillary glomerulonephritis and immunotactoid glomerulopathy. Journal of the American Society of Nephrology : JASN. 1998 Dec;9(12):2244-52. PubMed PMID: 9848778. Epub 1998/12/16. eng.
Its important , as it might indicate glomerular disease secondary to previous HCV infection, Common glomerular disease is membrano proliferative GN and FSGS. Presence of proteinuria and hematuria is warranting further investigation with kidney biopsy , with higher chance of refusal.of the donor.
Will you accept this DBD donor? History
A 56-year-old male DBD donor with HBsAg negative, HBsAb negative, HBcAb negative, HBeAg negative, HCV antibody positive, HCV PCR negative, HIV negative.
Will accept this donation but from HCV-positive donors we may experience inferior graft outcomes than those recipients of transplants from HCV-negative donors.
Treating HCV infection before transplantation can reduce the risk of HCV-associated renal dysfunction and progression.
This donor has HCV Ab +ve but HCV PCR -ve /and recipent has HCV -ve status, generally considered very low risk of transmission of HCV from an antibody-positive, PCR-negative.
Will you accept this donor as a live donor if the recipient is also HCV positive?
Hepatitis C antibody positive donor organs are offered to hepatitis C positive recipients. If a donor tests positive for antibody to hepatitis C, additional testing like PCR is done to check for actual viral presence in blood.
Yes Iwill accept this donor as HCV+ to HCV+ Kidney Transplantation has been successful in North American centres, with 40 HCV-positive recipients receiving 12 weeks of DAA therapy. All patients achieved a sustained virologic response at 12 weeks (SVR12) with good tolerance of treatment and 100% 1-year graft survival.
Researchers have made significant progress in HCV+ to HCV− Kidney Transplantation, using 12-week regimens of Gazoprevir and Elbasvir to demonstrate 100% SVR12. Different timepoints for the onset of DAA regimens have been used, with Goldberg et al initiating DAA therapy on post-transplant day 3 and Durand et al opting for a pre-emptive approach.
conditions that should be met in above case.
Kidney transplant candidates who are HCV RNA+ should undergo liver biopsy (current practice) to exclude fibrosis and the need for simultaneous liver-kidney transplantation.
If they are not cirrhotic (Fibrosis Stage 0-3), patients with living donors should be treated with DAAs pre-transplantation and proceed with transplantation.
In the absence of a living donor the two options would be: –
The first option would be to treat with DAAs pre-transplantation and list for a HCV- kidney like everyone else.
The second option would be to delay treatment and list for both HCV+ and HCV- kidneys, and then start HCV treatment with DAAs after transplantation. The delayed treatment approach may be beneficial for those who expect a prolonged waiting time on the deceased donor list or those who are at high risk for health deterioration on the waiting list (patients who are elderly or diabetic).
For patients with advanced liver disease (Fibrosis Stage 3), HCV treatment pre-transplantation may be prudent.
Assuming HCV PCR is not available, how would you manage?
In the absence of PCR, we should consider him positive.
It is advised to begin antiviral medication prior to kidney donation for chronic HCV carriers in circumstances where living donors have HCV infection or where PCR is not available.
Most HCV infections can be treated with short (8–12 week) DAA regimens. Sustained virologic response (SVR) after 12 weeks suggests an HCV cure.
Reference
Veroux M, Corona D, Sinagra N, et al. Kidney transplantation from donors with hepatitis C infection. World J Gastroenterol. 2014;20(11):2801-2809. doi:10.3748/wjg.v20.i11.2801
Doherty DT, Athwal V, Moinuddin Z, et al. Kidney Transplantation From Hepatitis-C Viraemic Donors:Considerations for Practice in the United Kingdom. Transpl Int. 2022;35:10277. Published 2022 May 3. doi:10.3389/ti.2022.10277
Zahid M. N. (2022). Transplantation of Organs from Hepatitis C Virus-Positive Donors under Direct-Acting Antiviral Regimens. Journal of clinical medicine, 11(3), 770. https://doi.org/10.3390/jcm11030770
Rao PS, Schaubel DE, Guidinger MK, et al. A comprehensive risk quantification score for deceased donor kidneys. Transplantation. 2009;88(2):231-236.
Thank you for your reply. This is a picture of a patient who was treated or cleared the HCV. The HCV antibodies indicated past infection. We need to make sure that there is no HCV-associated nephritis. Yes, for a living donor, I will exclude liver disease also. Well done. This is a model answer.
Regardless of recipients’ HCV status, HCV-infected donor kidneys are recommended. Hence, I will accept the patient.
Transplant centers must educate and inform patients before transplanting HCV-infected kidneys into HCV-uninfected recipients. Patients should understand the risks and benefits of HCV-infected kidney transplantation, including DAA treatment.
When transplanting kidneys from HCV-infected donors to HCV-uninfected recipients, transplant centers should confirm DAA availability for early post-transplantation.
Will you accept this donor as a live donor if the recipient is also HCV-positive? If yes, what are the conditions that should be met?
If the recipient is HCV-uninfected, HCV-infected potential living kidney donors who do not have cirrhosis should receive HCV treatment before donation. If they achieve sustained virologic response, no hepatic or extra-hepatic manifestations, and remain otherwise eligible to be a donor, they can be accepted for donation.
If the recipient is also HCV-positive then the approach is different. However, donation is still accepted. According to studies, receiving kidney transplants from HCV-positive donors does not result in an increase in the morbidity or death of the recipients who are HCV-positive.
Laboratory and imaging examinations should be carried out in order to assess the recipient’s liver’s current condition; nevertheless, a liver biopsy is required for confirmation if the results are inconclusive or raise a high suspicion of cirrhosis.
Assuming HCV PCR is not available, how would you manage the case?
In the absence of PCR, we should consider him positive.
It is advised to begin antiviral medication prior to kidney donation for chronic HCV carriers in circumstances where living donors have HCV infection or where PCR is not available. Most HCV infections can be treated with short (8–12 week) DAA regimens. Sustained virologic response (SVR) after 12 weeks suggests an HCV cure. Hence, this approach lessens the potential of HCV transmission to receivers with HCV RNA negative or superinfection with a different genotype among recipients with HCV RNA positive.
Thank you for your reply. This is a picture of a patient who was treated or cleared the HCV. The HCV antibodies indicated past infection. We need to make sure that there is no HCV-associated nephritis. Yes, for a living donor, I will exclude liver disease also.
Yes I will accept this donor with hepatitis C Abs positive and HCV PCR negative
presence of hepatitis c Abs either false report or prior infection has been resolved
if there are risk factors for hepatitis c or HCV exposure within the last 6 months for hepatitis c infection repeat HCV nucleic acid testing.
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
yes I will accept this living donor
counseling the recipient about hepatitis c infection risk and treatment and its medication.
HCV PCR for the donor if PCR negative, prior infection, can proceed for transplantation
HCV-infected living donors (HCV PCR positive) be considered for treatment before or shortly after transplantation with DAA therapy depending on the time of transplantation
hepatitis c positive donor if has no liver fibrosis can receive treatment
Assuming HCV PCR is not available, how would you manage the case?
Depending on the urgency of the transplantation, can proceed if not better to do PCR before transplant to know the situation and post transplant will follow up the recipient if develop HCV Ab or high liver enzyme I will start DAA
Referenc
from the lecture
. Denniston MM, Jiles RB, Drobeniuc J, et al. Chronic hepatitis C virus infection in the United States, National Health and Nutrition Examination Survey 2003 to 2010. Ann Intern Med 2014;160:293‐300. [PMC free article] [PubMed] [Google Scholar]
Thank you for your reply. This is a picture of a patient who was treated or cleared the HCV. The HCV antibodies indicated past infection. We need to make sure that there is no HCV-associated nephritis. Yes, for a living donor, I will exclude liver disease also. Well done. This is a model answer.
Yes, this deceased donor can be accepted even with HCV antibody positive, the nucleic acid testing of HCV PCR is negative.
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Yes, this donor can be approved for donation after monitoring of HCV viral load frequent times, liver functions, and hepatology consultation is mandatory along with Fibroscan if requested to ensure the abolished risk of HCV transmission even by different genotype rather than the recipient.
Regarding the recipient being HCV positive antibody and nucleic acid testing by PCR suggests initiation of DAAs as soon as possible according to co-ordination between hepatology and transplant centre together ,after assessment of liver enzymes ,hepatic tissue by fibroscan to elaborate whether the patient may require simultaneous liver kidney transplantation or not.
Assuming HCV PCR is not available, management would be totally depending on close frequent monitoring of HCV status in the recipient after transplantation ,without any delay in performing renal transplantation as the risk of remaining on waiting list and dialysis is by far more hazardous than undergoing renal transplantation ,this also requires counselling the recipient and obtaining a consent , along with checking the insurance system for the availability of DAAs if the recipient converted into HCV seropositive and needed treatment .
Another option after consenting the recipient is to initiate the DAA therapy and ezetimibe prior to renal transplantation in a prophylactic protocol for the perioperative period up to 7 days before discharge to home.
Thank you for your reply. This is a picture of a patient who was treated or cleared the HCV. The HCV antibodies indicated past infection. We need to make sure that there is no HCV-associated nephritis. Yes, for a living donor, I will exclude liver disease also.
A 56-year-old male DBD donor had Sr. Cr 78 µmol/L ====>
HBsAg, HBsAb, HBcAb, HBeAg, HBeAb ==> -ve HIV (negative) HCVAb (positive), HCV PCR (negative)==> may be ==> No active HCV infection , or cleared or treated HCV infection, or false-positive antibody.
Will you accept this DBD donor?
Yes, I will accept this DBD donor, as donor is HCV PCR negative, but antibody positive, which means there is no active HCV infection or replication.
Our Center Protocol (MAVIRET) (Glecaprevir / Pibrentasvir) and Ezetimibe
We are given Maviret(3 tablets) and Ezetimibe 10 mg ==> one dose pre-op then same dose for seven days ==> Ensure post-op dose is given within 24 HR from pre-op dose
HCV-positive donors may experience worse graft outcomes than recipients of transplants from HCV-negative donors.
Patients should be advised about the advantages and hazards of receiving an HCV-infected kidney transplant, also regarding the requirement for DAA therapy.
The recipient just needs to be counselled regarding the past HCV infection in the donor. Treating HCV infection before transplantation may reduce the risk of HCV-associated renal dysfunction and progression. Finally, very low risk of transmission of HCV from an antibody-positive, PCR-negative.
KDIGO-2022 guidelines:
Kidney transplantation is the best therapeutic option for patients with CKD G5 irrespective of presence of HCV infection. (1A)
After assessment of liver fibrosis, HCV-infected potential living kidney donors who do not have cirrhosis should undergo HCV treatment before donation if the recipient is HCV-uninfected; they can be accepted for donation if they achieve sustained virologic response (SVR) and remain otherwise eligible to be a donor. (Not Graded)
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Yes, I will accept the HCV positive live donor for HCV negative recipient.
BTS guidelines suggest that a course of therapy to cure a R- patient receiving a D+ organ would be less than the cost of dialysis for one year.
HCV D+/R- transplantation followed by early DAA therapy would result in only a transient, usually rapidly curable infection.
The donor needs to undergo AST-to-Platelet Ratio Index (APRI) and ultrasound done. If the APRI score is >0.8 or the ultrasound suggests significant or advanced liver disease, then an opinion from a suitably qualified liver specialist should be sought.
D+/R- recipient should undergo HCV RNA at 1 week, 2 weeks and 6 months. Whenever the PCR is positive, then the recipient needs to start DAA therapy within 3-10 days of the first positive PCR.
Proper consent of recipient is needed regarding all the complications and risk of HCV transmission and small risk of drug resistance HCV disease in recipient.
KDIGO-2022 GUIDLINES:
All kidney transplant candidates with HCV be evaluated for severity of liver disease and presence of portal hypertension prior to acceptance for kidney transplantation. (2D)
Patients with HCV, compensated cirrhosis and no portal hypertension undergo isolated kidney transplantation while patients with decompensated cirrhosis or clinically significant portal hypertension (i.e., hepatic venous pressure gradient ≥10 mm Hg or evidence of portal hypertension on imaging or exam) undergo a simultaneous liver-kidney transplantation. (1B) ,Those with mild-to-moderate portal hypertension should be determined on a case-by-case basis.
Referring patients with HCV and decompensated cirrhosis for combined liver-kidney transplantation. (1B)
Timing of HCV treatment in relation to kidney transplantation (before vs. after) should be based on donor type (living vs. deceased donor), waitlist times by donor type, center-specific policies governing the use of kidneys from HCV-infected deceased donors, and severity of liver fibrosis. (Not Graded)
All kidney transplant candidates with HCV be considered for DAA therapy, either before or after transplantation. (1A)
HCV-infected kidney transplant candidates with a living kidney donor be considered for treatment before or shortly after transplantation depending on the anticipated timing of transplantation. (2B)
Kidney transplant recipients being treated with DAAs be evaluated for the need for dose adjustments of concomitant immunosuppressants. (1C)
HCV-infected kidney transplant recipients should be tested at least every 6 months for proteinuria. (Not Graded)
Assuming HCV PCR is not available, how would you manage the case?
I Will accept the donor with HCV antibody positive and will consider him as HCV positive.
I will start peri operative DAA and would monitor him closely with PCR in the follow-up.
HCV positive donor, if the time to transplant is >24 weeks, I will treat the liver donor with
DAA and document SVR before transplant.
KDIGO-2022 GUIDLINE:
All kidney donors be screened for HCV infection with both immunoassay and NAT (if NAT is available). (1A)
Patients previously infected with HCV who achieved SVR before transplantation undergo testing by NAT 3 months after transplantation or if liver dysfunction occurs. (2D)
REFRENCESS:
Lecture of Professor May Hassaballah in HCV and kidney transplant
KDIGO-2022 guidelines
European Best Practice Guidelines for Renal Transplantation. Section I: Evaluation, selection and preparation of the potential recipient. Nephrol Dial Transplant 2000, 15 (suppl 7): 3-38.
Potluri VS, Goldberg DS, Mohan S, et al. National Trends in Utilization and 1-Year Outcomes with Transplantation of HCV-Viremic Kidneys. J Am Soc Nephrol 2019; 30: 1939-1951.
Ronit Patnaik, MD, Eugenia Tsai. Hepatitis C Virus Treatment and Solid Organ Transplantation. Gastroenterology & Hepatology Volume 18, Issue 2 February 2022. UK Position Statement on the use of Organs from Hepatitis C Viraemic Donors and Increased Infectious Risk Donors in Hepatitis C Negative Recipients
Our Center Protocol (MAVIRET) (Glecaprevir / Pibrentasvir) and Ezetimibe
We are given Maviret(3 tablets) and Ezetimibe 10 mg ==> one dose pre-op then same dose for seven days ==> Ensure post-op dose is given within 24 HR from pre-op dose
yes i accept after proper counseling / KTx is associated with better overall survival regardless of HCV status, this scenario low risk may be due to old or treated infection, passive Ab due to blood transfusion ( require history of any blood transfusion ), false positive,…etc
require monitoring of recipient post transplantation and treating Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
For living donor with HCV positive…….if time allow better to treat the donor then transplantation while if recipient already positive…. Yes you can accept with treating recipient with different protocols either before or after transplantation
in HCV positive recipient it is crucial to consult with hepatobiliary physian regarding the liver status , whether the patient need combined liver/ kidney transplantation or kidney transplantation alone
Thank you for your reply. This is a picture of a patient who was treated or cleared the HCV. The HCV antibodies indicated past infection. We need to make sure that there is no HCV-associated nephritis. Yes, for a living donor, I will exclude liver disease also.
Yes I would accept this DBD donor. HCV Ab positive with a negative HCV PCR suggests:
A past infection that was cleared
A false negative test
If this was a live donor and the recipient is HCV positive
Yes, I would accept this donor
A hepatologist should be consulted
The recipient should be assessed for cirrhosis – whether compensated or decompensated and the hepatic venous pressure gradient (HVPG). If the patient has decompensated liver cirrhosis and/or HVPG of more than 10 mmHg, then he should be considered for both liver/kidney transplant. The decision should also be made as to when to treat the recipient – pre-transplant or post-transplant. The HCV genotype should be determined. If the patient does not have rapidly progressive cirrhosis, then he can be treated post-transplant, thereby reducing his waiting time. If he has rapidly progressive cirrhosis, he should be treated pre-transplant.
The problem with post-transplant treatment is that it can sometimes delay treatment due to getting approval from the insurance
Assuming HCV PCR was not available:
This would raise an ethical dilemma as one would not be sure if the patient has HCV infection
In this case the organ, if possible should go someone who is HCV positive so that the recipient can receive treatment with the directly acting antiviral agents
If there is no HCV positive recipient, then the potential recipient should be counseled before the transplant. After the transplant, frequent monitoring of the HCV PCR should be carried out – after one week, 2 weeks then at six weeks. If the HCV RNA is positive, DAA should be started immediately
Kidney International (2022) 102 (Suppl 6S), S129–S205
Thank you for your reply. This is a picture of a patient who was treated or cleared the HCV. The HCV antibodies indicated past infection. We need to make sure that there is no HCV-associated nephritis. Yes, for a living donor, I will exclude liver disease also.
Will you accept this DBD donor? The possibility of anti HCV+ve /PCR –ve can be:
· Previous HCV infection
· False positive
· Previously treated HCV Yes, I will accept this patient kidneys, because of low risk of trasmitting hepatitis C virus infection in the recipient from anti HCV+/PCR- donors.
The recipient should be screened as follow: do HCV PCR at 3-7 days post Tx, repeated by day 10-14, then by 6 weeks post-transplant, if negative reassurance and no need for DAA therapy, if positive at any stage of screening, then start DAA within 3-10 days of positive test for 12 weeks, and confirm sustained viral response. Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met? Yes, I will accept this donor as a live donor to an HCV positive recipient. Need to do HVC PCR, LFT , coagulation profile
Hepatologist evaluation of both donor and recipient for portal hypertension, and assessment of hepatic fibrosis (fibro scan or biopsy), If the potential recipient is having advanced liver fibrosis, then need to go for simultaneous liver kidney transplantation.
I would start DAA for both donor and recipient before transplantation, if time allowed before transplant, and achieving HCV cure, before kidney donation.
Assuming HCV PCR is not available, how would you manage the case? If HCV PCR is not available will consider the donor as HCV Positive would go ahead for transplantation, with frequent monitoring of HCV PCR
Do HCV PCR at 3-7 days post Tx, repeated by day 10-14, then by 6 weeks post-transplant, if negative reassurance and no need for DAA therapy, if positive at any stage of screening, then start DAA within 3-10 days of positive test for 12 weeks, and confirm sustained viral response.
Reference 1.(KDIGO guideline) TREATMENT OF HCV IN KIDNEY TRANSPLANTRECIPIENTS
2- Position Statement on the use of Organs from Hepatitis C Viraemic Donors and Increased Infectious Risk Donors in Hepatitis C Negative Recipients(BTS)
Thank you for your reply. Well done Sumit. This is a picture of a patient who was treated or cleared the HCV. The HCV antibodies indicated past infection. We need to make sure that there is no HCV-associated nephritis. Yes, for a living donor, I will exclude liver disease also. Well done. This is a model answer.
DBD Potential donor with anti HCV Ab +ve , but HCV PCR –ve, and negative HBV serology. Causes of anti HCV+ve /PCR –ve : · Low level of virus load to be detected < 25 copies. · Previous HCV infection · False positive – connective tissue disease example SLE · ? Recent blood transfusion with anti HCV · Drug abusers cleared HCV infection · In babies of mothers with anti HCV +ve
Will you accept this DBD donor?
Yes, I will accept this patient kidneys, because of low risk of acquiring hepatitis C virus infection in the recipient from anti HCV+/PCR- donors. But the if the recipient is anti HCV –ve, then I will highlight the relative risk of graft loss more when having anti HCV-ve donors, but however, being transplanted is better than being long time on waiting list, and on dialysis. The recipient should be screened as follow: do HCV PCR at 3-7 days post Tx, repeated by day 10-14, then by 6 weeks post-transplant, if negative reassurance and no need for DAA therapy, if positive at any stage of screening then start DAA within 3-10 days of positive test for 12 weeks, and confirm sustained viral response. Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met? Yes, I will accept this donor as a live donor to an HCV positive recipient. Will send the recipient and donor for a hepatologist, for evaluation of portal hypertension, and assessment of hepatic fibrosis, as in a potential recipient with advanced liver fibrosis can go for simultaneous liver kidney transplantation. I would start DAA for both donor and recipient before transplantation, if time allowed before transplant, and achieving HCV cure, before kidney harvesting. Or, I will consider early start of DAA therapy, in order to prevent the deleterious consequence (fibrosing cholestatic hepatitis) that could occur in 10% of such cases, and other extrahepatic manifestations such as cryoglobinemia, vasculitis and PTLD. This would be explained to the patient as the decrease wait time to transplant, reduce mortality. Assuming HCV PCR is not available, how would you manage the case? I would go ahead for transplantation, with frequent monitoring as mentioned above, and when become positive I will start treatment with DAA. References: (1) Seeff LB. Natural history of chronic hepatitis C. Hepatology. 2002 Nov;36(5 Suppl 1):S35-46. doi: 10.1053/jhep.2002.36806. PMID: 12407575. (2) Daloul R, Pesavento TE, Goldberg DS, Reese PP. A review of kidney transplantation from HCV-viremic donors into HCV-negative recipients. Kidney Int. 2021 Dec;100(6):1190-1198. doi: 10.1016/j.kint.2021.06.034. Epub 2021 Jul 6. PMID: 34237327. (3) Czarnecka P, Czarnecka K, Tronina O, Baczkowska T, Durlik M. Utilization of HCV viremic donors in kidney transplantation: a chance or a threat? Ren Fail. 2022 Dec;44(1):434-449. doi: 10.1080/0886022X.2022.2047069. PMID: 35260039; PMCID: PMC8920354. (4) Kucirka LM, Singer AL, Ros RL, Montgomery RA, Dagher NN, Segev DL. Underutilization of hepatitis C-positive kidneys for hepatitis C-positive recipients. Am J Transplant. 2010 May;10(5):1238-46. doi: 10.1111/j.1600-6143.2010.03091.x. Epub 2010 Mar 26. PMID: 20353475. (5) Chascsa DM, Mousa OY, Pungpapong S, Zhang N, Chervenak A, Nidamanuri S, Rodriguez E, Franco D, Ryland K, Keaveny AP, Huskey JL, Smith M, Reddy KS, Taner CB, Vargas HE, Aqel BA. Clinical outcomes of hepatitis C treatment before and after kidney transplantation and its impact on time to transplant: A multicenter study. Am J Transplant. 2018 Oct;18(10):2559-2565. doi: 10.1111/ajt.14931. Epub 2018 Jun 8. PMID: 29758123.
Thank you for your reply. This is a picture of a patient who was treated or cleared the HCV. The HCV antibodies indicated past infection. We need to make sure that there is no HCV-associated nephritis. Yes, for a living donor, I will exclude liver disease also. Well done. This is a model answer.
Our deceased donor is HCV antibody is positive, but HCV PCR is negative.
Which carries three possibilities .
A-No active HCV infection.
B-Cleared or treated HCV infection.
C-False positive antibody. Will you accept this DBD donor?
Yes, I will .
As our donor is HCV positive by serologic testing but NAT negative (nonviremic) and these donors have not been documented to transmit HCV infection(1). Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Yes, I will.
As studies shown that long-term outcome of HCVR+ transplanted with kidneys from HCVD+ seems good in terms of patient survival, graft survival and liver disease and HCVD+ was not a significant risk factor for mortality, graft failure and liver disease among HCVR+.(2) Hepatic conditions to be met for the recipient might be compensated cirrhosis, or early fibrosis with absence of portal hypertension, will go ahead to transplant and then treat with DAA after the surgery for 12 weeks according to the genotype with strict follow up. However, if there is decompensated cirrhosis and portal HTN > 10mmHg with hepatologist assessment, will look for simultaneous liver and kidney transplantation and then treat the recipient with DAA after the surgery.
Close follow-up of patients with careful monitoring for early detection of post-transplant liver complications might have been decisive. Assuming HCV PCR is not available, how would you manage the case?
I will go with transplantation considering our donor as HCV PCR positive, then follow up recipient HCV PCR as per BTS guidelines if came positive I will treat with DAAs. References:
1- (KDIGO guideline) TREATMENT OF HCV IN KIDNEY TRANSPLANTRECIPIENTS 2- Position Statement on the use of Organs from Hepatitis C Viraemic Donors and Increased Infectious Risk Donors in Hepatitis C Negative Recipients(BTS)
3-Morales JM, Campistol JM, Domínguez-Gil B, et al. Long-term experience with kidney transplantation from hepatitis C-positive donors into hepatitis C-positive recipients. Am J Transplant. 2010;10(11):2453-2462. doi:10.1111/j.1600-6143.2010.03280.x.
1-You were offered kidneys from a 56 -year-old male DBD (donor after brain stem death) donor who suffered from SAH (grade 5) complicating cerebral aneurysm. His retrieval S Cr was 78 µmol/L. Virology was reported as follows: HBsAg negative, HBsAb negative, HBcAb negative, and both HBeAg and HBeAb are negative. HCV antibody is positive, but HCV PCR is negative. HIV is negative.
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Hepatitis C antibody positive donor organs are offered to hepatitis C positive recipients.
If a donor tests positive for antibody to hepatitis C, additional testing is done to check for actual virus in the blood.
Yes Iwill accept this donor
HCV+ to HCV+ Kidney Transplantation
HCV+ to HCV+ Kidney Transplantation has been successful in North American centres, with 40 HCV-positive recipients receiving 12 weeks of DAA therapy.
All patients achieved a sustained virologic response at 12 weeks (SVR12) with good tolerance of treatment and 100% 1 year graft survival.
Recipients can benefit from the safe expansion of the donor pool with good outcomes which has now become established practice.
HCV+ to HCV− Kidney Transplantation
Researchers have made significant progress in HCV+ to HCV− Kidney Transplantation, using 12 week regimens of Gazoprevir and Elbasvir to demonstrate 100% SVR12.
Different timepoints for the onset of DAA regimens have been used, with Goldberg et al initiating DAA therapy on post-transplant day 3 and Durand et al opting for a pre-emptive approach.
what are the conditions that should be met?
Kidney transplantation candidates who are HCV RNA+ should continue to undergo liver biopsy (current practice) to exclude cirrhosisand the need for simultaneous liver-kidney transplantation.
If they are not cirrhotic (Fibrosis Stage 0-3), patients with living donors should be treated with DAAs pre-transplantation.
In the absence of a living donor, these patients have two options:-
1- The first is to be treated with DAAs pre-transplantationand list for a HCV- kidney like everyone else.
2-The second option is to delay treatment and list for both HCV+ and HCV- kidneys, then receive HCV treatment with DAAs after transplantation (of note, the authors recommend consideration of the delayed treatment approach only for patients with genotype 1).
The delayed treatment approach may be particularly beneficial for patients who expect to have a prolonged waiting time on the deceased donor list (listed in a center with a long waiting time, blood type O or B) or those who are at high risk for health deterioration on the waiting list (patients who are elderly or diabetic).
For patients with advanced liver disease (Fibrosis Stage 3), HCV treatment pre-transplantation may be prudent.
Assuming HCV PCR is not available, how would you manage the case?
Direct Acting Antivirals (DAA) are the standard HCV treatment, and tests are used to diagnose the infection and confirm the clearance of viral replication.
Serological assays detect antibodies and nucleic acid tests detect RNA genomes to confirm active infection.
PCR testing requires time and trained laboratory personnel, increasing costs.
HCV-antigen testing is a serological assay that directly detects a viral protein, providing a positive result as soon as the virus component is present.
It is cheaper and requires less special training than PCR testing, but can miss people with low viral loads.
Testing strategies included HCV-antibody followed by PCR testing, antibody-antigen testing, and PCR test alone, with a second test 12 weeks after treatment completion to confirm SVR.
HCV-antigen and PCR tests were assumed to be 100% sensitive, and all detected patients were treated with DAAs and 98% achieved SVR.
Sadeghimehr M, Bertisch B, Negro F, et al. Hepatitis C core antigen test as an alternative for diagnosing HCV infection: mathematical model and cost-effectiveness analysis. PeerJ. 2021;9:e11895. Published 2021 Sep 10. doi:10.7717/peerj.11895
Veroux M, Corona D, Sinagra N, et al. Kidney transplantation from donors with hepatitis C infection. World J Gastroenterol. 2014;20(11):2801-2809. doi:10.3748/wjg.v20.i11.2801
Doherty DT, Athwal V, Moinuddin Z, et al. Kidney Transplantation From Hepatitis-C Viraemic Donors:Considerations for Practice in the United Kingdom. Transpl Int. 2022;35:10277. Published 2022 May 3. doi:10.3389/ti.2022.10277
Zahid M. N. (2022). Transplantation of Organs from Hepatitis C Virus-Positive Donors under Direct-Acting Antiviral Regimens. Journal of clinical medicine, 11(3), 770. https://doi.org/10.3390/jcm11030770
what is your decision in the last question? What if both PCR,and NAT are not available.!
My decision go to transplant
Recipients of kidney transplants from HCV-RNA-positive deceased donors had 5-year mean allograft survival, that was not statistically different from HCV-RNA–negative kidney recipients during the direct-acting antiviral era.
Begin the post-operative DAA, and in the follow-up, PCR would be used to constantly monitor him.
Rao PS, Schaubel DE, Guidinger MK, et al. A comprehensive risk quantification score for deceased donor kidneys. Transplantation. 2009;88(2):231-236.
Durand CM, Bowring MG, Brown DM, et al. Direct-acting antiviral prophylaxis in kidney transplantation from hepatitis C virus–infected donors to noninfected recipients. Ann Intern Med. 2018;168(8):533-540.
as per the recent recommendations organs from hepatitis C infected donors may be transplanted into uninfected recipients
with the following precautions
· consent to receive a HCV D+ organ
· should be avoided in recipients with advanced fibrosis or cirrhosis.
· To be seen by a liver specialist
· longitudinal testing for hepatitis C RNA of the recipient post transplant to ensure appropriate and early intervention if HCV transmitted AS FOLLOW
HCV PCR day 3-7——-If negative repeat day 10-14 ——– negative repeat 6 week post transplant ——- negative then manage as standard recipient
At any time positive PCR Start DAA within 3-10 working days of frist positive PCR
if PCR for recipient is not available The approach will be the same I will accept and then frequent monitor(same previous approach
UK Position Statement on the use of Organs from Hepatitis C Viraemic Donors and Increased Infectious Risk Donors in Hepatitis C Negative Recipients
I will accept the donor as he is PCR negative. Being positive for HCV antibodies is not a contraindication for kidney donation as there is no clear history of risky behavior such as IV drug abuse which might predispose to reinfection. Similarly, there is no history of failed therapy or SVR.
Transplanting HCV positive donor kidney to HCV positive recipient was proved to be effective approach in shortening the waiting time on transplant list, as DAA is effectively treating the donor post transplantation. Tha landmark studies Thinker and Expander advocated the utilization of HCV infected donors with either vigilant approach with low threshold to treat, once HCV infection diagnosed. Prophylactic treatment started prior to transplantation as majority of recipients would be converted to HCV positive infection.
No consensus is known about best method to approach those patients with potential HCV positive donors.
I would suggest close observation and follow up of the patients with positive donors and to implement treatment once diagnosed with HCV infection as success rate with DAA therapy exceed 95%.
Reference:
1]Pagan et al.Should my patient accept a kidney from a hepatitis C virus-infected Donor?.Kidney 3601[2]:p127-129,Feb.2020
Will you accept this DBD donor? Yes, I would accept this DBD donor, as the donor is HCV PCR negative, but antibody positive, which means there is no active HCV infection or replication.
The recipient just needs to be counselled regarding the past HCV infection in the donor.
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Yes, I would accept the HCV positive live donor for HCV negative recipient.
BTS guidelines suggest that “a course of therapy to cure a R- patient receiving a D+ organ would be less than the cost of dialysis for one year”
HCV D+/R- transplantation followed by early DAA therapy would result in only a transient, usually rapidly curable infection.
The donor needs to undergo AST-to-Platelet Ratio Index (APRI) and ultrasound done.
If the APRI score is >0.8 or the ultrasound suggests significant or advanced liver disease, then an opinion from a suitably qualified liver specialist should be sought.
D+/R- recipient should undergo HCV RNA at 1 week, 2 weeks and 6 months.
Whenever the PCR is positive, then the recipient needs to start DAA therapy within 3-10 days of the first positive PCR.
Proper consent of recipient is needed regarding all the complications and risk of HCV transmission and small risk of drug resistance HCV disease in recipient.
Assuming HCV PCR is not available, how would you manage the case?
We would still accept the donor with antibody postive and would consider him as HCV positive.
We would like to start peri operative DAA and would monitor him closely with PCR in the follow-up.
UK Position Statement on the use of Organs from Hepatitis C Viraemic Donors and Increased Infectious Risk Donors in Hepatitis C Negative Recipients
Also is the in HCV positive donor, if the time to transplant is >24 weeks, I would like to treat the liver donor with DAA and document SVR before transplant.
Positive HCV antibody test in the presence of negative HCV RNA carries a low transmission risk.
The constellation of diagnostic tests in this donor is interpreted by one of the followings:
No active HCV infection
Cleared or treated HCV infection.
False-positive antibody test
=============================== Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Yes, I would accept this donor in the mentioned setting.
Promising long-term outcomes of HCV-seropositive recipients transplanted with kidneys from HCV-positive donors have been reported.
The recent increase in KTXs from HCV-infected donors into HCV-naive recipients is due to the availability of DAA medication & its administration around the time of donation, which reduces the likelihood of chronic HCV infection in the transplant recipient.
Securing DAA therapy post-transplant is essential.
Patients should be fully informed of the associated risks, including the potential of HCV treatment failure.
Consider the possibility of Inadvertent interactions with immunosuppressive therapy.
=============================== Assuming HCV PCR is not available, how would you manage the case?
I will assume that HCV RNA is positive, and will still accept the donor because there is no significant difference in 5-year allograft survival for recipients of HCV-RNA–positive versus HCV-RNA negative donor kidneys.
The 5-year mean allograft survival was 4.30 years for HCV-RNA–positive transplants vs 4.27 years for HCV-RNA–negative transplants.
References
Schaubel DE, Tran AH, Abt PL, Potluri VS, Goldberg DS, Reese PP. Five-Year Allograft Survival for Recipients of Kidney Transplants From Hepatitis C Virus Infected vs Uninfected Deceased Donors in the Direct-Acting Antiviral Therapy Era. JAMA. 2022;328(11):1102–1104. doi:10.1001/jama.2022.12868
Ronit Patnaik and Eugenia Tsai,Hepatitis C Virus Treatment and SolidOrgan Transplantation, Gastroenterology & Hepatology Volume 18, Issue 2 February 2022
1- yes , will accept the donor , the donor is HCV Ab positive with negative PCR means non viremic HCV.
2- yes will accept , provided that DAA will be given to the patient perioperative or post operative or within 90 days of transplantation, also liver biopsy of the recipient should be done to detect cirrhotic or not
3- if PCR is not available, will accept if there is no other option for any other donor and will start DAA perioperative for 3 months with close follow up by PCR
references:
1- lecture of prof May Hassaballah
2- Ronit Patnaik, MD, Eugenia Tsai. Hepatitis C Virus Treatment and Solid Organ Transplantation. Gastroenterology & Hepatology Volume 18, Issue 2 February 2022
Will you accept this DBD donor?
Yes, provide the recipient accepts the offer and gets consented to go with the transplantation from HCV +ve donor but negative PCR which indicates previous infection with SVR either following treatment with DAA or spontaneous clearance.
Will you accept this donor as a live donor if the recipient is also HCV-positive? If yes, what are the conditions that should be met?
KDIGO guidelines recommended that all kidney transplant candidates with HCV be considered for DAA therapy, either before or after transplantation (1A).
Factors that affect the timing of the treatment included the type of donor living vs DD (anticipate waiting time)The severity of liver fibrosis, and portal hypertension
the willingness of the patient and program to accept an organ from an HCV-infected donor.
Yes, provided that the recipient with HCV positive needs to do HCV RNA- PCR or NAT assay to confirm he is viremic or not and assess for any evidence of liver cirrhosis or portal hypertension
If F0 to compensated cirrhosis without portal hypertension still can go for isolated kidney transplantation and if the short term for transplantation is less than24 weeks preferred to be treated with DAA after transplantation while if the expected time for transplantation > 24 weeks then treatment can be done before or after transplantation, the patient should consent and risk stratification and benefit addressed and explained to him, also drug-drug interaction should be addressed especially with CNI and DAA
If the recipient with decompensated liver cirrhosis and moderate to severe portal hypertension hepatic venous pressure gradient > 10
mm Hg or evidence of portal hypertension on imaging he should go for dual liver and kidney transplantation before treatment
Mild to moderate portal hypertension should be considered case by case
the recipient has no evidence of HCV-related kidney disease like MGN, MPGN, proteinuria and
And after checking HCV PCR for both donor and recipient if positive should offer the DAA therapy for 12 weeks and assuring SVR before or after transplantation based on waiting time.
Assuming HCV PCR is not available, how would you manage the case?
All living kidney donors should be screened for HCV infection with immunoassay and NAT if seropositive (1). HCV NAT has a sensitivity of 85% to 100% and a specificity of 99% to 100% (2).
It is significant to differentiate between a seropositive and viremic donor when debating organ transplant from an HCV-positive donor.
An HCV-seropositive donor that is NAT positive (viremic) is considered to have an active infection and carriages a high risk for disease transmission while HCV positive but NAT negative (nonviremic) is considered to have either spontaneous clearance or effective treatment of infection or have a false-positive antibody result, with low risk for transmitting HCV infection.
However, Kidneys from HCV-infected donors can be offered to potential recipients regardless of HCV status, provided that national or regional laws and
regulations allow this practice and assuring the availability of the DAA therapy once indicated after transplantation with a high cure rate of> 95%
so still can go ahead with accepting this donor and provide a full explanation to the recipient. With possible HCV infection early after transplantation which mandates close and frequent HCV PCR monitoring with DAA availability once indicated References 1. Martin P, Awan AA, Berenguer MC, Bruchfeld A, Fabrizi F, Goldberg DS, Jia J, Kamar N, Mohamed R, Pessôa MG, Pol S, Sise ME, Balk EM, Gordon CE, Adam G, Cheung M, Earley A, Jadoul M. Executive Summary of the KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease. Kidney Int. 2022 Dec;102(6):1228-1237. 2. Patnaik R, Tsai E. Hepatitis C Virus Treatment and Solid Organ Transplantation. Gastroenterol Hepatol (N Y). 2022 Feb;18(2):85-94. PMID: 35505819; PMCID: PMC9053510.
Interpretation of this donor according his virology:
HBsAg / HBsAb / HBcAb / HBeAg / HBeAb——- (negative)
HCVAb (positive) / HCV PCR (negative)
HIV (negative)
This patient is negative to (HBV& HIV) but this patient has (HCV Ab positive) My impression;
(No active HCV infection , or cleared or treated HCV infection, or false-positive antibody) 1-Will you accept this DBD donor?
Yes; I will accept this DBD donor According KDIGO-2022 guidelines;
-Kidney transplantation is the best therapeutic option for patients with CKD G5 irrespective of presence of HCV infection. (1A)
-After assessment of liver fibrosis, HCV-infected potential living kidney donors who do not have cirrhosis should undergo HCV treatment before donation if the recipient is HCV-uninfected; they can be accepted for donation if they achieve sustained virologic response (SVR) and remain otherwise eligible to be a donor. (Not Graded) 2-Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Yes; I will accept this alive donoe (D+HCV/R+HCV)
-Considering Consultation with a hepatologist to ensure the patient is not at increased risk of progressive liver disease with deferred treatment.
-However, the patient needs to provide written informed consent to receive a kidney from an HCV-infected donor (even though the patient already is infected).
-When the expected waiting time for a kidney allograft from an HCV-infected donor is long, the patient should be offered HCV therapy before transplantation.
-Potential living donors with HCV infection should be treated for HCV as in the general population and liver fibrosis should be assessed.
-Kidney function and proteinuria should be monitored during and after DAA therapy. According KDIGO-2022 guidelines;
-All kidney transplant candidates with HCV be evaluated for severity of liver disease and presence of portal hypertension prior to acceptance for kidney transplantation. (2D)
-Patients with HCV, compensated cirrhosis and no portal hypertension undergo isolated kidney transplantation while patients with decompensated cirrhosis or clinically significant portal hypertension (i.e., hepatic venous pressure gradient ≥10 mm Hg or evidence of portal hypertension on imaging or exam) undergo a simultaneous liver-kidney transplantation. (1B) ,Those with mild-to-moderate portal hypertension should be determined on a case-by-case basis.
-Referring patients with HCV and decompensated cirrhosis for combined liver-kidney transplantation. (1B)
-Timing of HCV treatment in relation to kidney transplantation (before vs. after) should be based on donor type (living vs. deceased donor), waitlist times by donor type, center-specific policies governing the use of kidneys from HCV-infected deceased donors, and severity of liver fibrosis. (Not Graded)
-All kidney transplant candidates with HCV be considered for DAA therapy, either before or after transplantation. (1A)
-HCV-infected kidney transplant candidates with a living kidney donor be considered for treatment before or shortly after transplantation depending on the anticipated timing of transplantation. (2B)
-Kidney transplant recipients being treated with DAAs be evaluated for the need for dose adjustments of concomitant immunosuppressants. (1C)
-HCV-infected kidney transplant recipients should be tested at least every 6 months for proteinuria. (Not Graded) 3-Assuming HCV PCR is not available, how would you manage the case?
-All deceased donors should be tested for HCV NAT prior to organ procurement, and ideally before the organ is offered to potential recipients.
-HCV-NAT positive patients who are candidates for kidney transplantation should be evaluated for the presence of cirrhosis using either a noninvasive fibrosis-staging method or, on occasion, a liver biopsy. According KDIGO-2022 guidelines;
-All kidney donors be screened for HCV infection with both immunoassay and NAT (if NAT is available). (1A)
-Patients previously infected with HCV who achieved SVR before transplantation undergo testing by NAT 3 months after transplantation or if liver dysfunction occurs. (2D) References;
-Chascsa DM, Mousa OY, Pungpapong S, et al. Clinical Outcomes of Hepatitis C Treatment Before and After Kidney Transplantation and Its Impact on Time to Transplant: A Multi-Center Study. Am J Transplant 2018; 18: 2559-2565.
-Potluri VS, Goldberg DS, Mohan S, et al. National Trends in Utilization and 1-Year Outcomes with Transplantation of HCV-Viremic Kidneys. J Am Soc Nephrol 2019; 30: 1939-1951.
-Diethelm AG, Roth D, Ferguson RM, et al. Transmission of HCV by organ transplantation. N Engl J Med 1992; 326: 410-411.
-European Best Practice Guidelines for Renal Transplantation. Section I: Evaluation, selection and preparation of the potential recipient. Nephrol Dial Transplant 2000, 15 (suppl 7): 3-38.
Yes, HCV positive donor type here is positive by serology and negative PCR. The differential diagnosis of these are: previous treatment , spontaneous clearance of the HCV virus or false positive results. This donor as such has no contraindication for transplantation
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met? Yes, will accept him, criteria for HCV +ve donor to HCV +ve recipient are:
Absence of liver cirrhosis in both pairs
Absence of HCC in both pairs
CKD has been ruled out in the donor
Availability of DAA therapy for treatment of both donor & recipient
Counseling & consent
Ensure that the donor is treated before transplantation with a documented SVR3
Follow up of the donor & recipient
Assuming HCV PCR is not available, how would you manage the case?
I will ask for NAT test to be carried out on the donor stored sample if available for the seek of better definition of this donor.
NAT positive + HCV serology positive : This is active infection and high risk for transmission
NAT negative + HCV serology positive: This may be previously cleared infection, treated donor, or false positive results. This is a low risk for transmission
In absence of both of PCR & NAT, the organ can still be be taken for transplantation
The HCV negative recipient should be counsel and well informed about all these possibilities including the risk of contracting HCV
In any case DAA therapy should be available and started earlier once the recipient has agreed
Source:
-Hepatitis C virus treatment and solid organ transplantation by Ronit patnaik et al.
-UK position on the use of organ from HCV donors and increased infectious risk donors in Hepatitis negative recipients
Will you accept this DBD donor?
Yes, I will accept.
The recipient and the team must be aware of the positivity of the serological status and follow-up in the post-transplant outpatient clinic with programmed dosages of RT PCR HCV.
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Yes, it is possible.
However, extensive investigation of liver function and structure is necessary to avoid unnecessary transplantation and immunosuppression.
Impaired liver function (widened INR, low platelets, high bilirubin values), clinical conditions resulting from structural liver disease (ascites, collateral circulation, disorientation), and active neoplasms (hepatocarcinoma) are situations that would suspend transplantation immediately.
A positive viral load in a patient waiting for a deceased donor would not prevent the immediate initiation of medication. If there is a schedule for a living donor, the ideal is to proceed with the treatment and wait for its completion in twelve weeks with a sustained viral response.
Depending on renal function, ribavirin may be excluded if CrCl < 30 (which would occur in those awaiting transplantation).
Avoid induction with rATG and rituximab, prioritizing IL2R blockage.
Assuming HCV PCR is not available, how would you manage the case?
Monitor the recipient’s viral load frequently over the next two years and start a hepatitis C regimen if the viral load is positive.
Interferon-free schemes are preferable, in Brazil the most used scheme is Sofosbuvir with Ledispavir. Although the first has little interaction with immunosuppressants, the second can interact with everolimus and calcineurin inhibitors.
Will you accept this DBD donor? Yes i will accept Transplant facilities must make sure that patients receive education. Discussions with team to give informed consent before performing kidney transplants. Patients should be advised about the advantages and hazards of receiving an HCV-infected kidney transplant, Also regarding the requirement for DAA therapy.
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Yes Transplantation is possible;
Living donation is possible if there isn’t extensive hepatic fibrosis or indications of kidney dysfunction.
If both the donor and recipient have HCV, treatment of the donor may be postponed if the transplant is timely and helps the recipient (e.g., avoids dialysis for a recipient with poor vascular access), with few risks anticipated for the donor.
Regarding patient survival, graft survival, and liver disease, the long-term results of HCVR+ kidney transplantation with kidneys from HCVD+ patients appear promising.
Among HCVR+, HCVD+ did not significantly increase the risk of death, graft failure, or liver disease.
These results strongly imply that kidney transplantation from HCVD+ patients into HCVR+ patients is a secure long-term technique that aids in kidney preservation. Assuming HCV PCR is not available, how would you manage the case?
I will treat the recipient with DAAs if the HCV PCR results are positive and I will manage the recipient with close follow-up as per BTS guidelines. I will consider the potential donor as HCV positive.
Yes, with the following precautions:
We recommend that kidneys from HCV-infected donors be considered regardless of the HCV status of potential kidney transplant recipients (1C).
: When transplanting kidneys from HCV-infected donors into HCV-uninfected recipients, transplant centers must ensure that patients receive education and are engaged in discussion with sufficient information to provide informed consent. Patients should be informed of the risks and benefits of kidney transplantation with an HCV-infected kidney, including the need for DAA treatment.
: When transplanting kidneys from HCV- infected donors into HCV-uninfected recipients, transplant centers should confirm the availability of DAAs for initiation in the early post-transplant period
Will you accept this donor as a live donor if the recipient is also HCV-positive? If yes, what are the conditions that should be met?
After assessment of liver fibrosis, HCV-infected potential living kidney donors who do not have cirrhosis should undergo HCV treatment before donation if the recipient is HCV-uninfected; they can be accepted for donation if they achieve sustained virologic response (SVR), no hepatic or extrahepatic manifestations, and remain otherwise eligible to be a donor.
Living donors with HCV infection: We recommend antiviral therapy before kidney donation for chronic HCV carriers. Short (8–12 week) DAA regimens treat most HCV infections. After 12 weeks, sustained virologic response (SVR) indicates an HCV cure. Hence, this strategy reduces the possibility of HCV transmission to HCV RNA-negative recipients or superinfection with another genotype among HCV RNA-positive recipients.
Data are lacking on the safety of transplanting a kidney from an HCV-seropositive live donor who has had effective antiviral therapy into an HCV-negative recipient or an HCV RNA-positive recipient with a different genotype.
Assuming HCV PCR is not available, how would you manage the case?
Transplant facilities must educate and notify patients before transplanting HCV-infected kidneys into HCV-uninfected recipients.
Patients should be advised of the risks and advantages of HCV-infected kidney transplantation, including DAA therapy.
Start pan-genotypic DAA directly, until the genotype analysis appears.
Close monitoring of PCR(HCV) RNA and LFTs post-transplant
Just consider the donor with unavailable PCR as +ve and proceed from there ( assuming he is a DD)
But if it is a LD ! with unavailable lab facility then make sure ADD are available and proceed from there.
Survival would be better than patients on waiting list.[1]
Transplantation from HCV seropositive/RNA negative would have low risk of transmission.[2]
DAAs can be used to treat infection.[3]
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Studies suggest that morbidity and mortality of HCV-seropositive recipients are not increased by the transplantation of kidneys from HCV-seropositive donors.[4] in order to differentiate between compensated vs decompensated liver disease with portal hypertension, the following tests should be done if not conclusive or high suspicion of cirrhosis than can do liver biopsy. it would help to differentiate whether to do kidney transplant or liver kidney combine transplantation.
LFTs
HCV RNA
U/S Abdomen
AST to Platelets ratio
Elsastography
Assuming HCV PCR is not available, how would you manage the case?
HVC core antigen test should be performed in resource limited areas. Core antigen assay has sensitivity and specificity for detecting HCV viremia of approximately 93 and 99 percent.[5]
References
Abbott KC, Lentine KL, Bucci JR, Agodoa LY, Peters TG, Schnitzler MA. The impact of transplantation with deceased donor hepatitis c-positive kidneys on survival in wait-listed long-term dialysis patients. Am J Transplant. 2004 Dec;4(12):2032-7. doi: 10.1046/j.1600-6143.2004.00606.x. PMID: 15575906.
Dao A, Cuffy M, Kaiser TE, Loethen A, Cafardi J, Luckett K, Rike AH, Cardi M, Alloway RR, Govil A, Diwan T, Sherman KE, Shah SA, Woodle ES. Use of HCV Ab+/NAT- donors in HCV naïve renal transplant recipients to expand the kidney donor pool. Clin Transplant. 2019 Jul;33(7):e13598. doi: 10.1111/ctr.13598. Epub 2019 Jun 5. PMID: 31104346.
Kling CE, Perkins JD, Landis CS, Limaye AP, Sibulesky L. Utilization of Organs From Donors According to Hepatitis C Antibody and Nucleic Acid Testing Status: Time for Change. Am J Transplant. 2017 Nov;17(11):2863-2868. doi: 10.1111/ajt.14386. Epub 2017 Jul 8. PMID: 28688205.
Morales JM, Campistol JM, Domínguez-Gil B, Andrés A, Esforzado N, Oppenheimer F, Castellano G, Fuertes A, Bruguera M, Praga M. Long-term experience with kidney transplantation from hepatitis C-positive donors into hepatitis C-positive recipients. Am J Transplant. 2010 Nov;10(11):2453-62. doi: 10.1111/j.1600-6143.2010.03280.x. PMID: 20977636.
Freiman JM, Tran TM, Schumacher SG, White LF, Ongarello S, Cohn J, Easterbrook PJ, Linas BP, Denkinger CM. Hepatitis C Core Antigen Testing for Diagnosis of Hepatitis C Virus Infection: A Systematic Review and Meta-analysis. Ann Intern Med. 2016 Sep 6;165(5):345-55. doi: 10.7326/M16-0065. Epub 2016 Jun 21. PMID: 27322622; PMCID: PMC5345254.
Yes, I will accept this DBD because the interpretation of the result could be:
no active infection
cleared or treated HCV infection
false positive antibody
Will you accept this donor as a live donor if the recipient is also HCV-positive? If yes, what are the conditions that should be met?
-Conditions to be met for the recipient
a) compensated cirrhosis, or early fibrosis
b) absence of portal hypertension
c) kidney from HCV positive donor will improve the chances of transplantation
IF the above “a” and “b” conditions are met, but the living kidney is only available within 24 hours, I will go ahead to transplant and then treat with DAA after the surgery for 12 weeks according to the genotype
IF the above “a” and “b” conditions are met, and the living kidney will be available for more than 24 hours, I will treat the recipient with DAA for 12 weeks before the surgery according to the genotype
However, if there is
decompensated cirrhosis and portal HTN > 10mmHg
I will evaluate for simultaneous liver and kidney transplantation and then treat the recipient with DAA after the surgery
Condition for the donor (not graded)
Following assessment for liver fibrosis and exclusion of cirrhosis, the donor is advised to receive treatment for HCV with SVR before proceeding to donate the kidney
Assuming HCV PCR is not available, how would you manage the case?
As it has been stated in the KDIGO guideline that the risk of transmitting HCV infection from HCV PCR recipient to recipient is minimal, then I will go ahead with the transplantation if the recipient is confirmed to be positive for HCV PCR and treat with DAA according to genotype post-surgery
In addition, tests like Fibroscan, and liver biopsy can be done for the donor to detect the presence of fibrosis or cirrhosis, and the stage will determine if DAA can be used for treatment before the surgery
References
Michel Jadoul, Marina C. Berenguer, Wahid Doss, Fabrizio Fabrizi, Jacques Izopet, Vivekanand Jha et al. Executive summary of the 2018 KDIGO Hepatitis C in CKD Guideline
May A. Hassabalah. Kidney transplantation in HCV patient. Lecture
Ronit Patnaik, Eugenia Tsai. Hepatitis C Virus Treatment and Solid Organ Transplantation. Gastroenterology &Hepatology. 2022;18(2): 85-92
Thankyou , a wise plan if a donor PCR is not available is to consider him positive!
A practical algorithm is offered by BTS for that situation,quoted by your collegue Mohamad Esmat.
In general, Hepatitis C virus (HCV) infection causes varieties of kidney disease in native and transplanted kidneys. Kidney transplant recipients with HCV infection, if HCV is not treated after transplantation will have a worse patient and allograft survival after transplantation compared with kidney transplant recipients without infection.
The potential donor has HCV Ab positive and HCV PCR negative:
-Most likely represents prior infection that subsequently cleared spontaneously (or following successful therapy). -A false-positive antibody tests due to technical reasons. – passively acquired from blood transfusions. which unusually nowadays. -The amount of HCV RNA may be below the limit of detection of the assay. My answer it will be yes, I will accept the offer with close monitoring of recipient after transplantation initially with AB test and by PCR if Ab test came positive.
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
In this case we have a potential donor without prove of chronic HCV infection (Ab positive and PCR is negative).
In the other side we have a recipient with proved HCV infection, so the management will be as following:
Basically, HCV infection prior to transplantation, when not successfully treated, increases posttransplant morbidity and mortality,but patients with HCV infection have a lower mortality with transplantation compared with remaining on dialysis.
-Staging of liver disease (assessing extent of fibrosis) is a standard component of the evaluation of patients with HCV infection: Staging is initially performed with non-invasive testing, which include blood tests and imaging tests ; transient elastography (TE) or aspartate aminotransferase (AST)-to-platelet ratio index (APRI). -A liver biopsy may be needed.
-Results of these staging tests can tell regarding liver-related prognosis, selection of HCV treatment regimen, and the decision on kidney versus combined kidney-liver transplantation.
-If there is proved cirrhosis, patient indicated for portal hypertension assessment. If there is decompensated cirrhosis or portal pressure more than 10 mmHg, he will be indicated for combined kidney-liver transplantation.
-Anti viral therapy (DAAs) either pre or post transplantation, case by case as per availability of the donor.
Assuming HCV PCR is not available, how would you manage the case? I will consider the potential donor as HCV positive, and I will accept the offer And manage recipient with close follow up with HCV PCR as per BTS guidelines if came positive I will treat with DAAs.
Transplantation of a kidney from an HCV RNA +ve kidney donors directly causes HCV infection in the recipient .HCV infection has been associated with increased morbidity and possibly mortality in kidney transplant recipients , but recipients of kidneys from HCV seropositive /RNA positive donors still have better outcomes compared with those who remain on dialysis. First of all , i will accept this DBD donor with the -ve HCV PCR
If this donor was a live donor and the recipient was also HCV positive :
-Using kidneys from HCV-seropositive donors in HCV seropositive recipients may be a safe approach in the long term as the risk of increased mortality is overweighed by the survival benefits , as well as the effectivity of the DAA’s the may possibly cure HCV infection after the Tx.
–In 2018 the KDIGO guidelines recommended that kidneys from sero+ve donors should be given only to sero+ve recipients , however the use of HCV RNA -+ve kidneys in sero-ve recipients followed by early administration of DAA’s was describes in a variety of pilot trials with good results.
–In recipients with HCV liver staging should be done using non-invasive techniques after labs and chemistery , as elastography.Liver biopsy may be done occasionally .
–Candidates with decompensated cirrhosis , severe portal hypertension are listed for combined liver kidney Tx .
–DAA’s timing is selected accordingly either pre or post transplant along with monitoring and follow up.
–The British Viral Hepatitis Group has recently issued a position statement on the use of organs from hepatitis C viraemic donors in hepatitis C negative recipients- diagram attached . References :
1-Hand book of Transplantation -6th edition
2-KIDIGO-2018
3-BTS position statement
4-UP to date – HCV and kidney transplantation
HCV antibody is positive, but HCV PCR is negative==> therefore I will accept this donor
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
HCV antibody is positive, but HCV PCR is negative==> therefore I will accept this donor even he is a living donor
However, if the recipient has PCR HCV positive,
==>
we should evaluate the liver fibrosis and the portal prussure in the recipient
If there is decompensated cirrhosis or portal pressure more than 10 ==> the recipient needs SLK transplant
If No ==>then , we should know if the living donor will remain available more than 24 weeks
If yes ==> recipient will be treated before renal transplantation
If no ==> recipient will be treated after RTX
Assuming HCV PCR is not available, how would you manage the case?
In this case I will consider this deceased donor as HCV pos
Therefore if the recipient is also HCV pos ==> we will accept this donor and start post renal treatment DAA
If the recipient is HCV negative ==> we should evaluate the waiting list period and compare between comorbidities and mortalities staying on waiting list
We should inform the recipient about the risk of infection
Trial of Transplantation of HCV-Infected Kidneys into Uninfected Recipients
• Thinker trial:safety and efficacy of transplanting HCV genotype-1 viremic kidneys into HCV-negative recipients (10 pts)
• All recipients tested positive for HCV RNA on day 3 post-transplantation and were subsequently treated with elbasvir/grazoprevir (EBR/GZR)
• all patients achieved sustained virologic response 12 weeks after the end of treatment (SVR12) and showed good allograft function
The strategy of management of donor pos to recipient negative depending on BtS recommendations
1 recipient tested for PCR HCV in day 3- 7
If negative
2- The test is repeated in day 10-14 post transplantation
If negative
3- The test is repeated in 6 weeks post-transplant
DAA started 3 to 10 days after any positivity of PCR HCV
Prophylactic initiation
given right before transplantation and for 7 days
REFERENCES
1- Kidney Txin patients with HCV professor May A. Hassaballa lecture
2- (KDIGO guideline) TREATMENT OF HCV IN KIDNEY TRANSPLANTRECIPIENTS
3- Position Statement on the use of Organs from Hepatitis C Viraemic Donors and Increased Infectious Risk Donors in Hepatitis C Negative Recipients(BTS)
Will you accept this DBD donor?
Yes.
Check donors is not cirrhosis or fibrosis ,consult. With hepatologist.
If time allowed treat the dojor.otherwise both will revived DAA therapy postransplant for 12 months.
If not available or not known ,still donors could be accepted and HCV PCr foje pist trandplant to follow for infection.
Will you accept this DBD donor?
Yes, I will accept if the following are met:
prophylactic treatment with Elbasvir/grazoprevir 2-3 months starting D-1 before transplantation.
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
For living donor actually still minimal risk for cryoglobinemia even after treatment of HCV but if the donor still willing, I will accept if the following are met:
Assuming HCV PCR is not available, how would you manage the case?
References
I. KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease VOLUME 102 | ISSUE 6S | DECEMBER 2022 http://www.kidney-international.org
II. Patnaik R, Tsai E. Hepatitis C Virus Treatment and Solid Organ Transplantation. Gastroenterol Hepatol (N Y). 2022 Feb;18(2):85-94. PMID: 35505819; PMCID: PMC9053510.
It is well recognized that a subset of patients who contracts Hepatitis C virus (HCV) spontaneously clears the virus. Such individuals are anti-HCV antibody positive, yet HCV RNA PCR negative in the blood. While they have not been considered candidates for live kidney donation in the past, with the recent availability of novel anti-HCV drugs with >95% cure rates, they now represent a potential pool of donor candidates, especially since the risk for transmission of HCV to the recipient is extremely low. The investigators goal is to demonstrate that live kidney donation from anti-HCV positive, HCV RNA PCR negative individuals is safe and carries a negligible risk of viral transmission to the recipient.
https://www.clinicaltrials.gov/ct2/show/NCT02669966
Will you accept this DBD donor?
· The picture in this scenario indicates either a false positive blood test that requires confirmation of a prior infection that has been resolved or treated(no current active infection and no viremia).
· Yes, I will accept this donor with hepatitis C Abs positive and HCV PCR negative in view of low-risk of transmission (HCV positive donors can be accepted regardless of the HCV status of the potential kidney transplant recipient).
· Proper counseling and consenting of the recipient and follow up after 12 weeks post transplantation is required with NAT testing to confirm absence of the transmission that requires treatment. If the HCV PCR became positive, the patient should be treated with directly acting antivirals for 12 weeks.
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
· Yes, I will accept this donation( donor with no active disease or viremia) as HCV positive donors can be accepted regardless of the HCV status of the potential kidney transplant recipient.
· Conditions to be met:
· The donor does not have any cirrhotic changes after evaluation by the hepatologist and does not have any extra-hepatic renal manifestations like proteinuria or hematuria that indicates the presence of GN as MPGN, cryoglobuleinemia or membranous nephropathy.
· Donors with positive PCR(not in this scenario) should undergo HCV treatment before donation if the recipient is HCV-uninfected and they can be accepted for donation if they achieved a SVR.
Assuming HCV PCR is not available, how would you manage the case
· In HCV PCR is not available for any cause, I will consider the donor as positive PCR for HCV. I will check HCV PCR in the post-transplant period at day 3-day7 and day10 -day14 and 6weeks post-transplant, if remained negative, I will reassure the patient. Otherwise, i will initiate DAAs in the early post-transplant period. Transplantation of HCV-viremic organs into HCV-naive recipients followed by the use of DAA agents provides excellent patient and allograft survival.
References:
1. Kidney Disease: Improving Global Outcomes (KDIGO) Hepatitis C Work Group. KDIGO 2022 Clinical Practice Guideline FOR the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease. Kidney Int. 2022 Dec;102(6S):S129-S205.
2. Fontaine H, Alric L, Labreuche J, Legendre B, Louvet A, Antoine C, Legendre CM, Hazzan M, Kamar N, Dharancy S, Pol S, Duhamel A, Mathurin P. Control of replication of hepatitis B and C virus improves patient and graft survival in kidney transplantation. J Hepatol. 2019 May;70(5):831-838.
1. Ans; yes I will accept. As there is evidence of no any active infection.
2. Ans; yes,
As the donor still does not have infectivty and state no evidence of cirrhosis, and associated secondary other renal disease.
As per KDIGO guidelines HCV positive can donate organ. Just to confirm the genotype for further treatment.
3. Ans;
I will council the family for possible risk of HCV contamination, will follow with LFTs, ultrasonography of upper abdomen, and repeated HCV PCR test.
If any infection will start treatment.
sir there is no documented evidence of transmission risk in literature.
Will you accept this DBD donor?
I will accept him.
He has negative hepatic virology profile except for positive HCV antibody but HCV PCR is negative .
Which means he might have previous infection that was cleared spontaneously or with TTT and now he is not infective and no viral load detected and no risk of infection transmission.
occult HCV infection”- the presence of HCV RNA in peripheral blood mononuclear cells and organ tissue by ultrasensitive assays in the absence of detectable RNA in the serum.
However, this entity is itself controversial, and its significance is uncertain, with inadequately described risk of transmission.
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Yes I will accept him also.
In the past it was contraindicated but now with advances on DAAS treatment the current cure rates for HCV now exceed 95%.
A recent report demonstrated high cure rates even in the liver transplant setting, suggesting that immunosuppression does not impede eradication and that interactions between HCV and transplant drugs can be successfully managed.
But her as the donor is living both should receive treatment for HCV before transplantation, treated with sofosbuvir and ribavirin for 12 weeks. .
A group in Barcelona reported transplantation of a live donor kidney from a donor treated with an anti-HCV regimen that achieved a sustained virological response to her spouse with no transmission of infection.
It is also recommended to treat HCV infection before transplantation to reduce the risk of liver cirrhosis and HCV-associated renal disease ( such as cryoglobulinemia ).
Assuming HCV PCR is not available, how would you manage the case?
If HCV RNA by PCR of the donor is unavailable we can still proceed for transplantation with monitoring of recipient HCV RNA by PCR if infection transmition occurred ,start anti-viral ttt
References:
Live Kidney Donors with Positive Anti-HCV Antibody, But Negative HCV PCR. ClinicalTrials.gov Identifier: NCT02669966. 2020
Yes, i would accept this DBD donor as risk of HCV transmission is low
Yes, i would accept this donor as a live donor if the recipient is also HCV positive.
At first treatment of HCV positive recipient with DAA after genotype assessment. When HCV RNA undetectable then go for transplantation. Then do HCV PCR of the recipient on post transplant 3-7 day, 10-14 day and 6 weeks. If HCV PCR negative then reassure patient. If HCV PCR positive then start DAA within 3-10 working days
Assume that donor is HCV positive and start peri operative DAA.
Will you accept this DBD donor?
Yes
Will you accept this donor as a live donor if the recipient is HCV-positive? If yes, what are the conditions that should be met?
Yes,
However, we need to be sure that the donor has no evidence of liver cirrhosis and pristine urinalysis (no haematuria and no proteinuria) as the presence of these findings could suggest underlying renal pathology ie: MPGN, membranous, cryoglobulinaemia.
Assuming HCV PCR is not available, how would you manage the case?
Assume the donor PCR is positive and treat the recipients with DAA pre or immediately after transplantation (a few hours before to a median of 76 days after transplantation) (1)
References
Q1: Yes, I will proceed to transplantation, because positive serology with negative PCR for HCV, only indicates previous infection of HCV. According to KDIGO guideline, HCV-infected donors could be considered for TX with DAA therapy.
Q2; Yes, I will. According to KDIGO guideline, HCV positive donors regardless of the HCV status of the recipients, could donate their kidney.
HCV positive individuals, could donate their kidney only if:
1. Start the HCV treatment before TX, if the recipient is HCV negative.
2. There is no cirrhosis in the donor.
Q3: In this situation, it is better to consider the donor’s PCR positive. So, I will start treatment with DAA therapy and follow- up with repeated HCV PCR test after transplantation. Patient and graft survival are very good in HCV positive donors among recipients, but needs adequate information and informed consent.
Reference:
1.Jadoul, M., Awan, A. A., Berenguer, M. C., Bruchfeld, A., Fabrizi, F., Goldberg, D. S., Jia, J., Kamar, N., Mohamed, R., Pessôa, M. G., Pol, S., Sise, M. E., & Martin, P. (2022). KDIGO 2022 Clinical Practice Guideline FOR the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease. Kidney International, 102(6).
2.Patnaik, R., & Tsai, E. (2022). Hepatitis C Virus Treatment and Solid Organ Transplantation. In Gastroenterology and Hepatology (Vol. 18, Issue 2).
Will you accept the DBD donor?
The patient is offered a kidney from a 56 year old male DBS with no evidence of HBV or HIV…. The donor has negative HCV RNA PCR and anti HCV antibodies…This case has previous HCV infection in the past the details of which we are not able to elicit…I will accept this donor as there is low risk of transmission due to negative HCV RNA level….I will counsel the recipient for possible monitoring of the HCV viral load and initiation of DAA in the future if there is HCV RNA reactivation…weekly HCV RNA levels on day 7, 14 and 6 weeks post transplant.. KDIGO recommends to take the organ from HCV Positive donor regardless to the status of HCV of recipient
Will you accept this donor as a live donor if the recipient is also HCV positive?
HCV positive donor is giving the kidney to HCV positive recipient…HCV positive donors can be accepted regardless of the state of HCV positive state of the recipient as per KDIGO guidlelines….The donor should be evaluated for the presence of HCV genotyping to decide on antivirals if the HCV RNA quantitative is positive..USG abdomen for coarse echoes and fibroscan to rule out cirrhosis is a must..Living donation can be proceeded in the absence of fibrosis..IF the HCV RNA of the donor is positive and the recipient is negative the Live donor should be started on DAA. In this case the donor HCV RNA is negative, and donor need not be treated with DAA….
The recipient has to be evaluated in detail by LFT, Fibroscan, OGD scopy, Anti HCV status, HCV RNA quantitative analysis has to be done to rule out cirrhosis..F1,F2 fibrosis by fibroscan can be proceeded with kidney transplant alone and F3,F4 fibrosis needs combined liver and kidney transplant…
If both donor and recipient are HCV infected, DAA treatment of the donor can be delayed….if HCV RNA of the recipient is negative, donor due HCV has to be started on DAA immediately …
With the advent of DAA, it can be continued in the post transplant period with no interaction with immunosuppression….
Assumuing HCV PCR is not available, how would you manage the case? If the donor HCV PCR is not available, transplant can be proceeded with recipient testing for HCV RNA at a regular basis that is day 3, day 7, day 14 and after 6 weeks after transplant….
Yes, because this serological status and PCR indicate that the patient has already had the disease and is cured.
Yes, that would be really nice.
I would only try to perform HCV treatment prior to transplantation, but it could also be performed subsequently.
– A discussion with family members about the risks of HCV contamination would be necessary
– Conducting serial liver function tests, anti-HCV and PCR for HCV in the post-transplant period
– Execution of treatment if the receiver evolved with signs of HCV viral replication.
References:
– KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease VOLUME 102 | ISSUE 6S | DECEMBER 2022 http://www.kidney-international.org
– Patnaik R, Tsai E. Hepatitis C Virus Treatment and Solid Organ Transplantation. Gastroenterol Hepatol (N Y). 2022 Feb;18(2):85-94. PMID: 35505819; PMCID: PMC9053510.
1.Will you accept this DBD donor?
– Yes, it is well acceptable
– HCV Ab + / HCV RNA negative: indicate previous antiviral treatment or spontaneous clearance of the virus with increased immunity or even false positive results
– The chance of HCV transmission is very low, compared to those with RNA positive
– Outcomes even for HCV negative recipients favourable; it increased the organ pool and waiting time for HCV positive are as well as negative recipients.
– The recipient has to be counselled about the risk of HCV, need for antiviral treatment, high risk of graft dysfunction and mortality.
– But survival and QOL of patients received organs from HCV+ donors are far better than those on dialysis and waiting list.
– Checking for HCV-RNA -PCR results à positive viremia needs 12 weeks antivirals; if negative à no antiviral therapy, but monitoring every 3months.
2. Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
– yes, HCV+ donor for HCV+ recipient is acceptable;
– HCV infection in the potential kidney transplant recipient is not a contraindication to transplantation, as effective antivirals are available for both Pre- and Post transplant.
– In case of live donor with HCV+, we can have time to better the donor till the virus is undetectable before transplant.
– Higher risk of Hepatitis, renal allograft graft dysfunction / rejection and mortality, need to be explained.
– DAA -HCV-antiviral is effective and safe. 12weeks antiviral treatment started within hospital, post-transplant is recommended and SVR rate is nearly 100%.
– Need to ensure affordability and access to DAA
· Measures to avoid unfavourable outcomes:
– Staging of Liver disease (extent of fibrosis) in recipient – through APRI score (AST-to-platelet ratio index) and transient elastography (TE) which estimates the liver stiffness.
– liver biopsy is reserved for discordant non-invasive test results or when suspecting liver comorbidities
– Cirrhotic patients, need assessment of portal Pressure, to rule out PHT
Ø Chronic Hepatitis and compensated Cirrhosis with Portal Pressure <10, advised for antiviral treatment with Kidney transplant.
Ø Decompensated liver disease, compensated liver cirrhosis with severe portal hypertension à need combined liver-kidney transplant
(decompensated liver disease is characterized by decreased serum albumin and/ or hyperbilirubinemia, prolonged INR, ascites, hepatic encephalopathy
o Ensure reliable access to DAA
· timing of DAA therapy
– Treatment prior to transplant, if the patient has severe liver disease (e.g., decompensated liver cirrhosis), rapidly progressive liver disease, extrahepatic complications of HCV infection, lack of access to organs from donors with HCV infection, long anticipated waiting time on the transplant, living donor.
– If well matched cadaver organ is available right way, patient can go for renal transplant with early start of antiviral (-12 / 0 hour)
– Anti-viral Regimen depends on the HCV genotype – antiviral treatment history, underlying liver disease, drug-drug interactions, cost, availability.
– Expert Hepatologist should be taken on board for treating such cases
– Sofosbuvir has no drug-drug interactions with CNIs, MMF or mTORi, and has good SVR (90-98%) rate
– Monitoring for HCV-related kidney disease and liver disease
– atients with advanced fibrosis or cirrhosis have increased risk for HCC – AFP and Liver USG every 6months is recommended
– Surveillance for Renal and Liver problems as well as NODAT and PTLD
Assuming HCV PCR is not available, how would you manage the case?
– We have to consider him as HCV-RNA positive donor
– Counselling the recipient regarding the high risk of transmission and hence the need to start DAA therapy prior to transplantation (-12hr or 0-hr)
References
1. Terrault, Norah A. et al. International Liver Transplantation Society Consensus Statement on Hepatitis C Management in Liver Transplant Recipients. Transplantation 2017 May; 101 (5): 956-967
2. Patnaik R, Tsai E. Hepatitis C Virus Treatment and Solid Organ Transplantation. Gastro-enterlogy & Hepatology issue 2. February 2022. Gastroenterology & Hepatology 2022 Feb; 18 (2): 85-94
3.
Jandovitz N, Nair V, Grodstein E, Molmenti E, Fahmy A, Abate M, et al. Hepatitis C-positive donor to negative recipient kidney transplantation: A real-world experience. Transplant infectious disease : an official journal of the Transplantation Society. 2021 Jun;23(3):e13540. PubMed PMID: 33259125. Epub 2020/12/02.
Kamalkiran M, Ravikiran V, Shashidhar C, Prasad KVR, Yeldandi V. Kidney Transplantation from a Hepatitis C Virus-positive Donor to a Hepatitis C Virus-negative Recipient. Indian journal of nephrology. 2018 Nov-Dec;28(6):488-9. PubMed PMID: 30647508. Pubmed Central PMCID: PMC6309394. Epub 2019/01/17.
4. Pestana NF, Equi CMA, Gomes CP, et al. Aminotransferase-to-platelet ratio index and Fibrosis-4 index score predict hepatic fibrosis evaluated by transient hepatic elastography in hepatitis C virus-infected haemodialysis patients. European journal of gastroenterology & hepatology 2021 Dec;33(1S) Suppl: e260-e5. PubMed PMID: 33405422. Epub 2021/01/07.
5. Kiberd BA, Doucette K, Vinson AJ, Tennankore KK. Hepatitis C virus-infected kidney waitlist patients: Treat now or treat later? American journal of transplantation 2018 Oct;18(10): 2443-50. PubMed PMID: 29687948. Epub 2018/04/25.
6. KDIGO 2018 clinical practice guideline for the prevention, diagnosis, evaluation, and treatment of hepatitis C virus in chronic kidney disease
What is the chance of transmission of HCV in HCV antibody positive, HCV PCR negative?
· HCV Ab + / HCV RNA negative: indicate previous antiviral treatment or spontaneous clearance of the virus with increased immunity or even false positive results
· The risk of HCV transmission in this case is very low, compared to those with RNA positive.
· The risk of transmission is non with HCV Ab negative + HCV RNA negative.
Ref:
Patnaik R, Tsai E. Hepatitis C Virus Treatment and Solid Organ Transplantation. Gastro-enterlogy & Hepatology issue 2. February 2022. Gastroenterology & Hepatology 2022 Feb; 18 (2): 85-94
Is it important to check urine for proteinuria and haematuria for donor who had HCV infection? Why?
Yes
Donors with HCV infection – it is important to rule out HCV related nephropathies
Common glomerular pathologies – Mixed cryoglobulinemia, MPGN, Membranous glomerulonephritis. MPGN is most commonly associated with HCV infection
Less common pathologies – Membranous nephropathy (MN), FSGS, Thrombotic microangiopathies (TMAs), IgA nephropathy (IgAN)
Clinical Presentation – proteinuria, microscopic haematuria, hypertension, acute nephritis and nephrotic syndrome
Reference:
1. Ozkok A, Yildiz A. Hepatitis C virus associated glomerulopathies. World J Gastroenterol. 2014 Jun 28;20(24):7544-54. doi: 10.3748/wjg.v20.i24.7544. PMID: 24976695; PMCID: PMC4069286.
2. Johnson RJ, Willson R, Yamabe H, Couser W, Alpers CE, Wener MH, Davis C, Gretch DR. Renal manifestations of hepatitis C virus infection. Kidney Int. 1994 Nov;46(5):1255-63. doi: 10.1038/ki.1994.393. PMID: 7853784.
3. Latt N, Alachkar N, Gurakar A. Hepatitis C virus and its renal manifestations: a review and update. Gastroenterology & hepatology. 2012 Jul;8(7):434-45. PubMed PMID: 23293553. Pubmed Central PMCID: PMC3533219. Epub 2013/01/08.
4. Markowitz GS, Cheng JT, Colvin RB, Trebbin WM, D’Agati VD. Hepatitis C viral infection is associated with fibrillary glomerulonephritis and immunotactoid glomerulopathy. Journal of the American Society of Nephrology: JASN. 1998 Dec;9(12):2244-52. PubMed PMID: 9848778. Epub 1998/12/16.
Will You Accept this donor?
YES
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Donors liver status should be assessed. An ultrasound followed by a Fibroscan is needed to clarify the liver status.
If there is no advanced liver disease this living donor should be accepted.
Assuming HCV PCR is not available, how would you manage the case?
we should consider it as HCV positive and will treat with DAA in post transplant period
Will you accept this DBD donor?
· Yes. According to KDIGO 2022: They recommend that kidneys from HCV-infected donors be considered regardless of HCV status of potential kidney transplant recipients.
· Transplant centers must ensure that patients receive education and are engaged in discussion with sufficient information to provide informed consent.
· Patients should be informed of the risks and benefits of transplantation with an HCV infected kidney, including the need for DAA treatment
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
· Yes, as kidney transplantation is the best therapeutic option for patients with CKD G5 irrespective of the presence of HCV infection.
· kidney transplant candidates with HCV should be evaluated for severity of liver disease and presence of portal hypertension prior to acceptance for kidney transplantation
· Patients with HCV, compensated cirrhosis, and no portal hypertension undergo isolated kidney transplantation and patients with decompensated cirrhosis or clinically significant portal hypertension undergo a simultaneous liver–kidney transplantation
· HCV-infected kidney transplant candidates with a living kidney donor should be treated with DAA therapy before or shortly after transplantation depending on the anticipated timing of transplantation
Assuming HCV PCR is not available, how would you manage the case?
· If PCR not available he should be treated as HCV + with DAA.
KDIGO 2022 CLINICAL PRACTICE GUIDELINE FOR THE PREVENTION, DIAGNOSIS, EVALUATION, AND TREATMENT OF HEPATITIS C IN CHRONIC KIDNEY DISEASE
Yes, this DBD donor would be accepted.
Patient with HCV antibody indicates previous infection.
Donors who are HCV Ab positive are grouped as viremic and non-viremic based on NAT testing. Those with NAT positive are viremic. Those donors who are HCV Ab positive, but NAT negative can be transplanted to HCV negative recipients, but post-transplant NAT testing is recommended to confirm the lack of disease. In HCV negative recipients if de novo HCV infection occurs then direct antivirals should be started. Kidney from donors who are Hepatitis C Ab positive and NAT negative can be transplanted into HCV NAT positive recipients, DAA treatment should begin post-transplant. Although transplant between HCV NAT positive donors and HCV NAT positive recipients is recommended and post-transplant DAA treatment should be started with monitoring of PCR. Transplant of HCV NAT positive kidney to HCV negative recipient is possible with DAA treatment, and should be followed closely for potential complications.
Non availability of HCV PCR mean transplant is high risk and active HCV can not be ruled out
HCV antibody do not suggest active infection so we can proceed with transplant
donor urine should be tested for HCV associated nephropathy
DBD with -ve HBV and HCV antibody +ve with -ve PCR
Will you accept this DBD donor?
I will accept such donor as +ve HCV AB may due to previous infection or false +ve result.
A donor who is HCV antibody-positive/NAT-negative has an infection that spontaneously cleared or was successfully treated or a false-positive antibody result. Such patients have a very low risk of HCV transmission.
Furthermore, even at the list price of DAAs (the actual prices that the NHS pays are lower) the additional costs of transplanting recipients exposed to HCV with a kidney from a HCV antibody positive donor was cost-neutral in comparison with remaining on dialysis within 5 years following transplantation.
Recipient HCV PCR testing within 3 months of transplantation to monitor for HCV disease transmission.
Yes I will accept this donor
MDT must be included ,,, hepatologist consultant for evaluation of patient and donor health status ,portal hypertension,hepatic fibrosis and if hepatic failure present to consider both hepatic and renal transplant .
Both recipient and donor should be start on DAA to prevent post transplant complications fibrosing cholestatic hepatitis ,vasculitis and PTLD.
I will proceed transplant , HCV RNA may not yet be detectable and transplant recipients from these donors should be monitored for HCV in addition to HBV and HIV per the increased-risk donor testing protocols.
DAAs were initiated in a range between a few hours before renal transplant (RT) to a median of 76 days after RT.
Acceptance of the donor; yes based on the serology
Also, donation from HCV-infected live donor is accepted if HCV of the recipient is positive or negative serology with treatment of the donor prior to donation with achieving SVR to reduce the risk of hepatitis C associated nephropathy.
Testing of renal function, and testing for proteinuria and hematuria to rule out HCV related nephropathy for the donor prior to decide processing for transplantation.
-If HCV PCR not available:
Recipient with his family should be counselled regarding possibility of infection from HCV RNA Positive donor.
We should consider positive RNA by PCR for HCV and start DAA before transplantation. HCV RNA by PCR needs to be monitored at 7th day, 14th day and 6 weeks post-transplant and DAA continued till 2 weeks if positive.
References:
KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease Vol 102 | ISSUE 6S | DECEMBER 2022
Yes i will accepot this patient as a kidney donor as being HCv Ab positiv means that had the infection and now cleared or treated specially if his HCV RNA -.
We can accept this kidny without fear of HCV infection .
The estimated rate of spontanouse clearance is 20 to 45% depend on the age and immunity of the person .
There is a strong and likely causal association between chronic hepatitis C virus (HCV) infection and glomerular disease.
●The major glomerular diseases associated with HCV infection include the following
•Mixed cryoglobulinemia syndrome
•Membranous nephropathy
•Polyarteritis nodosa (PAN)
All patients with mixed cryoglobulinemia syndrome, membranoproliferative glomerulonephritis (MPGN) type I, membranous nephropathy, and PAN should be evaluated for possible underlying HCV infection. In addition, HCV-infected patients should be evaluated for proteinuria, hematuria, hypertension, and a reduced glomerular filtration rate (GFR). Patients who are found to have kidney abnormalities should undergo testing for cryoglobulins, hypocomplementemia, and a positive rheumatoid factor. A kidney biopsy should be considered in the setting of significant proteinuria and/or impaired kidney function.
In general, patients with severe and progressive HCV-associated glomerulonephritis should undergo antiviral treatment. Most patients with less severe glomerular disease associated with HCV should also have antiviral therapy provided they do not have decompensated cirrhosis. In patients who are selected for antiviral therapy, the specific regimen depends upon the estimated GFR (eGFR).
references
uptodate
1- I will accept him as the risk of transmission is low(seropositive but not viremic)
2- IF the recipient is positive:
We can accept the kidney
but requires:
3- IF PCR is not available:
1- send specimen for central labs and once result is available send to tx center
2- if other liver function of the donor is ok, we can accept it for suitable recepient
3- assessment of recipient HCV PCR:
Will You Accept this donor?
YES
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Donors liver status should be assessed. An ultrasound followed by a Fibroscan is needed to clarify the liver status.
If there is no advanced liver disease this living donor should be accepted.
Assuming HCV PCR is not available, how would you manage the case?
we should consider it as HCV positive and will treat with DAA in post transplant period
Yes.
considering D+ to R transplantation should be considered , across all solid organs within
set criteria, and recommended that such practice should take place within prospective research protocols.
the high morbidity and mortality rates for patients on the waiting list justify the utilisation of D+ organs.
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
viremic donor and a viremic recipient (D±/R+), DAA therapy in the posttransplantation
period should follow the policy of the transplant center, according to recent American
Association for the Study of Liver Diseases/Infectious Diseases Society of America and
transplant guidelines.
The use of HCV-viremic donors for HCV-viremic recipients (D+/R+) is acceptable in
routine clinical practice.
RFFRENCES:
1-Terrault, Norah A. et al .International Liver Transplantation Society Consensus Statement on Hepatitis C Management in Liver Transplant Recipients.Transplantation ,101(5):p 956-967, May 2017.
Consider patient as PCR positive and give DAA.
OUR CASE;
56 YR old male, DBD,SAH from cerebral aneurysm with a cr of 78
HBsAG ,HBcAB,HBeAG,HBeAB,HCV PCR,HIV -NEG,HCV ab +VE
Will you accept this donor?
Yes, this will decrease the waiting period and studies show good post transplant graft function. HCV is not a contraindication to donation and timing of treatment is determined on a case by case basis.
Will you accept this donor as a live donor if recipient too is HCV positive? If yes, what conditions should be met?
Assuming HCV PCR is not available, how would you proceed?
I would treat him as a viremic donor with a high risk of transmission and start DAA prior to transplantation. Elbasivir/Grazoprevir OD for 2-3/12 beginning 1/7 pr transplant.
REF;
1. You were offered kidneys from a 56 -year-old male DBD (donor after brain stem death) donor who suffered from SAH (grade 5) complicating cerebral aneurysm. His retrieval S Cr was 78 µmol/L. Virology was reported as follows: HBsAg negative, HBsAb negative, HBcAb negative, and both HBeAg and HBeAb are negative. HCV antibody is positive, but HCV PCR is negative. HIV is negative.
Issues/ concerns: –
– 56yo male, DBD, Grade 5 SAH complicating cerebral aneurysm
– retrieval sCr 78
– viral screen: – HBsAg negative, HBsAb negative, HBcAb negative, HBeAg negative, HBeAb negative, HCV Ab positive, HCV PCR negative, HIV Ab negative.
Will you accept this DBD donor? (1, 2)
– yes, I would accept this donor
– use of such organs expands the organ pool and decreases the waiting times for HCV-negative recipients and is associated with favourable outcomes
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met? (1, 2)
– yes, I would accept the donor as a live donor if the recipient is also HCV positive
– HCV infection in the potential kidney transplant recipient is not a contraindication to transplantation
– HCV infection increases the morbidity and mortality post-kidney transplant
– HCV infection treatment is effective and safe
– to avoid unfavourable outcomes, some measures/ conditions have to be put into place: –
– if cirrhosis is present, assess for portal hypertension prior to transplantation
– liver biopsy is reserved for discordant noninvasive test results or when suspecting liver comorbidities
– decompensated liver disease is characterized by decreased serum albumin and/ or hyperbilirubinemia, prolonged INR, ascites, hepatic encephalopathy
– indications for a combined liver-kidney transplant: – decompensated liver disease, compensated liver cirrhosis with severe portal hypertension
– timing of DAA therapy – DAA can be given before or after transplantation depending on several factors
– offer treatment prior to transplant if the patient has severe liver disease (e.g., decompensated liver cirrhosis), rapidly progressive liver disease, extrahepatic complications of HCV infection, lack of access to organs from donors with HCV infection, long anticipated waiting time on the transplant, living donor (4)
– basically, the timing of DAA therapy relative to the transplant depends on the waiting list advantage and the impact of delay on HCV-associated mortality especially in those with advanced fibrosis and cirrhosis (4)
– regimen selection depends on the HCV genotype, antiviral treatment history, underlying liver disease, drug-drug interactions, cost, availability
– Sofosbuvir can be used in all stages of kidney disease including
during dialysis
– Sofosbuvir has not been shown to have significant drug-drug interactions with CNIs, mycophenolate or mTORi
– should be able to assess for sustained virological response (SVR)
– in addition to the standard care/ monitoring following transplantation, kidney transplant recipients with HCV infection require close monitoring for HCV-related kidney disease and liver disease until the HCV infection has been fully treated
– patients with advanced fibrosis or cirrhosis post-transplant are at increased risk for HCC hence should be continuously monitored for such complications
– test for proteinuria using spot uPCR or 24-hour urine protein, every 6 months
– new onset proteinuria (i.e., uPCR >1g/g or 24hr-urine protein >1g) or microscopic hematuria without any other identifiable cause warrants a graft biopsy for light microscopy, immunofluorescence and electron microscopy
– kidney disease associated with HCV infection among kidney transplant recipients includes: -MPGN, MN, transplant glomerulopathy, renal thrombotic microangiopathy
– other complications include PTDM, PTLD
Assuming HCV PCR is not available, how would you manage the case?
– I would consider him as a HCV-positive viremic donor
– I would inform and counsel the potential recipient regarding the high risk of transmission and hence the need to start DAA therapy prior to transplantation
References
1. Jandovitz N, Nair V, Grodstein E, Molmenti E, Fahmy A, Abate M, et al. Hepatitis C-positive donor to negative recipient kidney transplantation: A real-world experience. Transplant infectious disease : an official journal of the Transplantation Society. 2021 Jun;23(3):e13540. PubMed PMID: 33259125. Epub 2020/12/02. eng.
2. Kamalkiran M, Ravikiran V, Shashidhar C, Prasad KVR, Yeldandi V. Kidney Transplantation from a Hepatitis C Virus-positive Donor to a Hepatitis C Virus-negative Recipient. Indian journal of nephrology. 2018 Nov-Dec;28(6):488-9. PubMed PMID: 30647508. Pubmed Central PMCID: PMC6309394. Epub 2019/01/17. eng.
3. Pestana NF, Equi CMA, Gomes CP, Cardoso AC, Zumack JP, Villela-Nogueira CA, et al. Aminotransferase-to-platelet ratio index and Fibrosis-4 index score predict hepatic fibrosis evaluated by transient hepatic elastography in hepatitis C virus-infected hemodialysis patients. European journal of gastroenterology & hepatology. 2021 Dec 1;33(1S Suppl 1):e260-e5. PubMed PMID: 33405422. Epub 2021/01/07. eng.
4. Kiberd BA, Doucette K, Vinson AJ, Tennankore KK. Hepatitis C virus-infected kidney waitlist patients: Treat now or treat later? American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2018 Oct;18(10):2443-50. PubMed PMID: 29687948. Epub 2018/04/25. eng.
KDIGO 2018 clinical practice guideline for the prevention, diagnosis, evaluation, and treatment of hepatitis C virus in chronic kidney disease
Will you accept this DBD donor?
Yes I will accept this donor.
The donor is HCV antibody positive with negative PCR hence this donor had HCV infection and was treated successfully thus has no risk of transmission.
The HCV antibody can remain positive indefinitely.
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Yes I would accept if this was living donation and both donor and recipient are positive.
The conditions to be met include:
Assuming HCV PCR is not available, how would you manage the case?
If the HCV PCR is not available it would be difficult to know whether the donor has acute infection or past infection which will translate to the risk of transmission.
I would continue with transplantation and counsel the recipient on the risk of HCV transmission.
If the recipient was HCV negative then HCV per would be done routinely in the post-transplantation period starting from 33-7 days post transplant, then 10-14 days post transplant and 6 weeks post transplant.
A positive PCR will warrant prompt initiation of DAA the preferred combination will be Glecaprevir/Pibrenatasvir or Sofosbuvir/Velpatasvir which are pan-genotypic and have minimal drug interaction.
Other tests that could be done include NAAT and antigen testing.
What is the risk of transmission of HCV in HCV antibody positive and HCV PCR negative?
The risk of transmission is low.
A positive HCV antibody and negative PCR indicates either a false positive test, or a patient who was successfully treated.
However in a small proportion of patients may be in the window period or reinfection posing a high risk of transmission.
Is it important to check for urine proteinuria and hematuria in a patient who had HCV infection?
Yes, to look for extra hepatic manifestation of HCV infection that include cryglobulinaemic vasculitis, membranous nephropathy, MPGN.
References
KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease VOLUME 102 | ISSUE 6S | DECEMBER 2022 http://www.kidney-international.org
UK Position Statement on the use of Organs from Hepatitis C Viraemic Donors and Increased Infectious Risk Donors in Hepatitis C Negative Recipients
DBD donor
Donor is HCV antibody positive but HCV PCR negative. Thus risk of disease transmission from donor to recipient is very low post transplant. Thus I would accept this donor.
If donor had HCV antibody positive along with HCV PCR negative, then it means the donor has an active infection, and risk of disease transmission from donor to recipient post transplant would be 100%.
However, in our scenario, since the donor is HCV PCR negative, he has had a previous HCV infection which is not active at present, and would pose very low percentage of risk for transferring to the recipient post transplant.
Patient should however be monitored closely for HCV infection and given appropriate antiviral therapy since occult infection can occur.
Live donor, HCV positive recipient
Yes, I would accept this donor.
Donor has to be treated for HCV with DAAs prior to the transplant and check for viral load, along with sustained virologic response according to KDIGO guidelines (2018).
KDIGO guidelines also recommend pairing NAT positive live donor with NAT positive recipient to limit risk of HCV transmission and loss of organs from the donor pool. Both donor and recipient need to be treated appropriately with DAAs.
HCV positive recipients with compensated cirrhosis but without portal hypertension may be treated with DAAs post transplant if they have access to a living kidney donor without a long wait time.
Management if HCV PCR is not available
In the case that HCV PCR is not available, it is difficult to ascertain whether the donor has an active infection (in which case it is 100% transferable to recipient) or only had a previous infection which was treated with antiviral therapy.
I would counsel the recipient about the risk of transmission potentially, and ask for informed consent. I would accept this donor if the recipient has been on the waitlist for a few years and is eager to get transplanted and given that we cannot find any other suitable donor.
The recipient would need antiviral therapy post transplant for 8-12 weeks assuming that transmission of HCV infection has taken place from the donor. HCV PCR has to be done intermittently in this 12 week period.
References
= Will you accept this DBD donor? Yes
= Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
**Yes
**conditions: No signs of nephopathy and donnor receives DAA 12 weeks prior to Tx to minimize the risk of transmission. Recipient should have surviellence post transplant and provide informed consent.
= Assuming HCV PCR is not available, how would you manage the case?
will go a head and do HCV PCR at 3-7 days post Tx, repeated by day 10-14, then by 6 weeks post-transplant, if negative reassurance and no need for DAA therapy, if positive at any stage of screening, then start DAA within 3-10 days of positive test for 12 weeks, and confirm sustained viral response.
Will you accept this DBD donor?
Yeas I will accept.
This donor had : HBsAg negative, HBsAb negative, HBcAb negative, and both HBeAg and HBeAb are negative but he had positive HCV antibody with negative HCV PCR which may be occult HCV infection within denoted organ which can activated after immune supressions ,therefor HCV investigations must be done after transplantation, if positive treatment must given.
Also HCV antibody positive may false positive result.
Over all this case is very low risk of transmission.
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Yes I will accept.
Exclude liver cirrhosis and HCC in both
Rule out CKD in donor
Available DAA for both donor and recipient
Informed consent
Negative PCR
Treatment of donor pre donation with sustained virologic response
Assuming HCV PCR is not available, how would you manage the case?
Enzyme immunoassay can be done if NAT is not available
Short course of DAAT regimen can be given and SVR assessed
Reference
Kidney Disease: Improving Global Outcomes. KDIGO clinical practice guidelines for the
prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease.
Kidney Int. 2008; 73 (suppl 109):S1–S99
Approach for transplanting kidney from HCV + donor to HCV – recipient
The main challenge is transmission of HCV from donor to the recipient with possibility of HCV related hepatic affection and extra hepatic complications including GN, so the following approach should be done in order to improve outcome:
Selecting appropriate donor
Selecting appropriate recipient
Use of prophylactic therapy including Elbasvir/grazoprevir and /or sofosbuvir in D+R- status
Different protocols available according to different studies:
To conclude … 3 protocols are available, prophylactic therapy, early treatment and late treatment. Late initiation of treatment is associated with the worst outcome since it is associated with viremia related complications, on the other hand prophylactic treatment leads to giving treatment to patient that may not require.
Monitoring
Will you accept this DBD donor?
Yes I will accept if the following are met:
And I will initiate either prophylactic treatment with Elbasvir/grazoprevir once daily for 2-3 months starting from day -1 before transplantation or upon detection of viremia with regular check of serum ALT, HCV PCR, renal functions, proteinuria post transplantation and keep in mind drug-drug interaction when using non- Pangenotypic DAA
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Yes I will accept if the following are met:
And I will initiate either prophylactic treatment with Elbasvir/grazoprevir once daily for 3 months starting from day -1 before transplantation with regular check of serum ALT, HCV PCR, renal functions, proteinuria post transplantation and keep in mind drug-drug interaction when using non- Pangenotypic DAA.
Assuming HCV PCR is not available, how would you manage the case?
References
1- Utilization of HCV viremic donors in kidney transplantation: a chance or a threat?
Dear All
What is the chance of transmission of HCV in HCV antibody positive, HCV PCR negative?
Thanks prof,
Thanks
Thanks; Our Prof.
-Clinical Interpretation of case with HCVAb (positive) /HCV PCR (negative);
-In this situation, the reactive anti-HCV antibody most likely represents prior infection that subsequently cleared spontaneously (or following successful therapy) or a false-positive antibody test due to technical reasons.
-False-negative tests for RNA are unusual when sensitive quantitative or qualitative tests with a low level of detection (eg, <25 international units/mL) are used.
-The absence of detectable HCV RNA essentially confirms the absence of chronic HCV infection.
-The estimated rate of spontaneous clearance of virus after infection is 20 to 45% depending upon the age and immune status of the individual at the time of infection.
(With low risk of transmission)
-The seroprevalence of HCV infection in the general population is approximately 1 to 3 % worldwide, although prevalence varies from region to region.
-However, before HCV RNA testing became mandatory, HCV positivity was defined only by HCV seropositivity, without consideration of the patient’s viremic status.
-Recipients of HCV-seropositive/RNA-negative kidneys appear to have the same graft and patient survival as recipients of HCV-seronegative kidneys.
Rationale;
-HCV seropositivity does not necessarily mean HCV RNA positivity, which indicates an active replicating infection.
-The best data regarding prevalence among deceased organ donors are from a study of 13,667 potential organ donors evaluated between 2004 and 2008 by 17 organ procurement organizations in the United States; HCV seroprevalence was 3.45% among normal-risk potential donors and 18.2 % among high-risk potential donors.
-In one study of 55 living, related potential donors, the seroprevalence of HCV was 3.6 %.
-The reported seroprevalence of HCV infection among kidney transplant recipients is approximately 1.8 to 8 %.
-In one report that included 468 HCV-seropositive recipients, 5- and 10-year survival were not different between recipients of kidneys from HCV-seropositive and HCV-seronegative donors.
References;
-HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C. Joint panel from the American Association of the Study of Liver Diseases and the Infectious Diseases Society of America.(Accessed on January 01, 2020).
Briefly;
Low risk of transmission with out confirmed ratio.
Thanks
Seropositive HCV (HVCAb+/RNA-)differs from viremic patient in risk of transmission, seropositive HCV had no documented risk of HCV infection transmission.
Thanks
In a scenario with positive HCV antibody and a negative HCV PCR, the implication is either a false positive anti-HCV antibody, or a past infection which either got cleared spontaneously, or after being treated.
Organs from such patients can be safely used without any increased risk of HCV transmission (1,2). The risk of transmission can be there in case the HCV PCR is falsely negative (3).
References:
Thanks
HCV antibody positive NAT negative patient poses low risk of transmission while HCV antibody positive NAT positive donor has active infection and poses 100% risk of transmission post transplant.
Reference :
Rawashdeh B, Hulse J, et al. Transplant of a kidney from a hepatitis C viremic donor to a naive recipient without viral transmission : a case report. Am J Case Rep.2021; 22:e927532-2-e927532-4. doi: 10.12659/AJCR.927532
Thanks
This represents either past infection with resolution post treatment or a false positive with a very low chance of transmission.
this mean either previously treated infection or false positive results
and the risk of transmission is very low
What is the chance of transmission of HCV in HCV antibody positive, HCV PCR negative? (1, 2)
– a positive HCV Ab and a negative HCV RNA denotes no evidence of current HCV infection hence further testing using a different HCV Ab assay helps differentiate past (resolved) infection from a false positive result
– Occult HCV infection (OCI) is defined as presence of HCV RNA in hepatocytes or peripheral blood mononuclear cells (PBMCs) with no detectable HCV RNA in the serum
– occult HCV infection can be seropositive OCI (HCV Ab positive and serum HCV RNA negative) or seronegative OCI (HCV Ab negative and serum HCV RNA negative)
– additional investigations are needed to determine the infectivity of patients with occult HCV infection
References
1. Austria A, Wu GY. Occult Hepatitis C Virus Infection: A Review. Journal of clinical and translational hepatology. 2018 Jun 28;6(2):155-60. PubMed PMID: 29951360. Pubmed Central PMCID: PMC6018308. Epub 2018/06/29. eng.
2. Castillo I, Bartolomé J, Quiroga JA, Barril G, Carreño V. Hepatitis C virus infection in the family setting of patients with occult hepatitis C. Journal of medical virology. 2009 Jul;81(7):1198-203. PubMed PMID: 19475603. Epub 2009/05/29. eng.
Is it important to check urine for proteinuria and haematuria for donor who had HCV infection? Why?
it is important to check for proteinuria or hematuria as HCV can cause:
-Cryoglobulin
-MPGN
-membranous
-FSGS
-IgA
should be negligible,
Antibodies might persist for a longer time after clearance of the viral infection, which is indicated by negative quantitative PCR test for HCV nucleic acid.
Is it important to check urine for proteinuria and haematuria for donor who had HCV infection? Why? (1, 2)
– yes, it is important to check urine for proteinuria and hematuria
– chronic HCV infection can cause different forms of kidney disease hence the need to monitor proteinuria and hematuria
– the most common renal manifestations of HCV infection are:
– MPGN is most commonly associated with HCV infection
– other glomerulonephritides associated with HCV include:
References
1. Latt N, Alachkar N, Gurakar A. Hepatitis C virus and its renal manifestations: a review and update. Gastroenterology & hepatology. 2012 Jul;8(7):434-45. PubMed PMID: 23293553. Pubmed Central PMCID: PMC3533219. Epub 2013/01/08. eng.
2. Markowitz GS, Cheng JT, Colvin RB, Trebbin WM, D’Agati VD. Hepatitis C viral infection is associated with fibrillary glomerulonephritis and immunotactoid glomerulopathy. Journal of the American Society of Nephrology : JASN. 1998 Dec;9(12):2244-52. PubMed PMID: 9848778. Epub 1998/12/16. eng.
HCV seropositive, but negative HCV PCR have very low risk of transmission. In cases who both positive serology and PCR, all recipients will be infected by HCV after kidney transplantation and need treatment with DAA and monitoring.
Thank you Prof
Chance of transmission is low
Will you accept this DBD donor?
Yes, this donor may be accepted. Since the donor has a normal renal function and he is HBsAg negative, HBsAb negative, HBcAb negative, HCV antibody is positive, but HCV PCR is negative and both HBeAg and HBeAb are negative, he has had a previous HCV infection but is now non-infective.
However, an occult HCV infection within the donated organ may flare post-transplant due to immuno-suppression. Hepatitis C testing should be done post-transplant and treatment given if positive.
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Yes, donation from HCV-infected live donor is acceptable whether HCV status of the recipient is positive or negative.
Conditions that need to be met:
Donors should receive treatment for HCV before donation if the recipient is HCV-uninfected until they achieve sustained virologic response (SVR). Treating HCV infection before transplantation can reduce the risk of HCV-associated renal dysfunction.
The assessment of renal function, urine protein and RBC to exclude HCV associated nephropathy has to be undertaken for the donor prior to deciding whether the organ can be harvested.
Assuming HCV PCR is not available, how would you manage the case?
The patient (recipient) and his/her family need to be well counseled about the possible risk of infection by HCV RNA Positive donor.
If HCV RNA by PCR of the donor is unavailable, we have to assume a positive RNA by
PCR for HCV and commence DAA prior to transplant surgery. HCV RNA by PCR needs to be checked in the post-transplant period at 7th day, 14th day and 6weeks post-transplant and DAA continued upto 12 weeks if positive.
References:
KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease VOLUME 102 | ISSUE 6S | DECEMBER 2022 http://www.kidney-international.org
Thanks, acknowledged
Yes I will accept this donor because availability of DAAT will treat HCV if it transmitted to recipient
If patient NAT negative means HCV cleared spontaneously or successfully treated
Prophylaxis by DAAT should be given
Thanks, acknowledged
I will accept this donor because his viral load is negative. With the extended pool of donations, such patients are utilized. we need to make sure about end organ damage. Regarding the kidneys, we need to make sure about proteinuria. A renal biopsy can be taken (in my opinion) to check for silent glomerular disease. For liver donation, we need to ensure the absence of cirrhosis. The longer the duration of HCV positivity, the more the risk for glomerular pathology (MPGN, Cryoglobulinemia etc. )
If this donor was a live donor, I would have time to check for eligibility. This should be discussed with the recipients and weighed: staying on dialysis with worse outcomes vs being transplanted with a higher risk of viral infections, including CMV virus
If the HCV RNA is not available (in this DBD case), I need to ensure the availability of direct antiviral therapy. Direct antiviral therapy can be started peri or post-operatively. but we need to ensure support and availability. Both THINKER and EXPANDER-1 trials showed accepted results for HCV viremic donations to HCV-negative patients.
,,,,,,,,
Pagan, Javier1; Ladino, Marco1,2; Roth, David1. Should My Patient Accept a Kidney from a Hepatitis C Virus–Infected Donor? Kidney360 1(2):p 127-129, February 2020. | DOI: 10.34067/KID.0001012019
)
Thanks, acknowledged
What is the chance of transmission of HCV in HCV antibody positive, HCV PCR negative?
Will you accept this DBD donor?
Yes, I accept for donation. HCV Ab positive indicates previous infection. PCR is negative as well.
Will you accept this donor as a live donor if the recipient is HCV-positive? If yes, what are the conditions that should be met?
Yes, I will accept this donor and the following conditions to be met:
· Donor kidneys should not have any sign of nephropathy; renal function tests, urine analysis for RBC, albumin.
· It is recommended that donors with HCV infection should receive direct anti-viral treatment (DAA) for HCV before transplantation for 12 weeks to minimize the risk of HCV transmission to HCV-negative recipients
· The recipient should undergo anti-viral treatment post-transplant.
· Informed consent.
Assuming HCV PCR is not available, how would you manage the case?
Reference:
· Ronit Patnaik et.al. Hepatitic C Virus Treatment and Solid Organ Transplantation. Gastroenterology & Hepatology Volume 18, Issues 2, February 2022.
· KDIGO 2022
· UpToDate
Thanks, acknowledged
What is the chance of transmission of HCV in HCV antibody positive, HCV PCR negative?
Yes, we can accept; (after availabilty od DAA), which helps reducing waitlisting recipients and reduce mortality while being on dialysis, and to expand donors pool
With low risk of infection.
5 and 10 years survival rates was 84.8% to 72.7% respectively, by one study
HCV+ve live donor/HCV R+ve
We can accept with the following
If PCR is not available
References
Belga S, Doucette KE. Hepatitis C in non-hepatic solid organ transplant candidates and recipients: a new horizon. World J Gastroenterol. 2016;22(4):1650-1663. 2. Kwong AJ, Kim WR, Lake JR, et al. OPTN/SRTR 2019 annual data report: liver. Am J Transplant. 2021;21(suppl 2):208-315. 3. Health Resources & Services Administration. Organ donation statistics. https:// http://www.organdonor.gov/learn/organ-donation-statistics/detailed-description#fig1. Updated October 2021. Accessed November 7, 2021.
Wolfe RA, Ashby VB, Milford EL, et al. Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N Engl J Med. 1999;341:1725-1730.
Centers for Disease Control and Prevention. Hepatitis C.
Will you accept this DBD donor?
Yes, I will accept this DBD donor.
This donor is negative for HBV and HIV.
This donor is HCV Ab positive and HCV PCR negative which means either
Spontaneous clearance of infection, treated infection or false negative results.
Recipients of kidneys from HCV-Ab positive/ HCV-RNA negative donors showed the same patient and graft survival compared to recipients of HCV-Ab negative kidneys.
The recipient must be counselled before transplantation about the protentional risk of HCV infection from infected donor.
The recipient should be tested for HCV RNA within first week post-transplantation then on day 14 than at 6 weeks. If the recipient turns up positive, HCV treatment should be initiated within 3-10 days of first positive HCV RNA.
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Yes, I will accept this donor.
Conditions to be met:
1- Donor kidneys doesn’t show nephropathy (kidney function tests, urine analysis for blood and proteins and potential biopsy). It is recommended that donors with HCV infection should receive direct anti-viral treatment (DAA) for HCV before transplantation for 8-12 weeks to minimize the risk of HCV transmission to HCV-negative recipients or super-infection with another genotype in HCV-positive recipients. SVR (Sustained Virologic Response) at 12 weeks is considered a marker of HCV cure.
2- Recipient assessment: compensated or decompensated liver cirrhosis, presence of portal hypertension, HCV genotpe. There are limited data about the safety of renal transplantation into HCV negative recipient or HCV positive with different HCV genotype from a living donor with HCV positive who undergone successful antiviral treatment. The recipient should undergo anti-viral treatment post-transplant.
3- Availability duration of the living donor for at least 24 weeks so the decision to treat before or after transplantation can be decided.
4- Willingness of both donor and recipient.
KDIGO 2018 recommended that kidneys from HCV-positive/RNA positive donor should be given only to HCV positive recipients.
Assuming HCV PCR is not available, how would you manage the case?
I will consider it as HCV positive, so the recipient should be counselled before proceeding for transplantation. The recipient should be tested for HCV RNA within first week post-transplantation then on day 14 than at 6 weeks. If the recipient turns up positive, HCV treatment should be initiated within 3-10 days of first positive HCV RNA.
References:
Uptodate
Fontaine H, Alric L, Labreuche J, et al. Control of replication of hepatitis B and C virus improves patient and graft survival in kidney transplantation. J Hepatol 2019; 70:831.
Thanks, acknowledged
What is the chance of transmission of HCV in HCV antibody positive, HCV PCR negative?
· Will you accept this DBD donor?
Yes, as he HCV PCR negative and risk of transmission is very low. Transmission rate of 1.9%, in the setting of a falsenegative NAT at the time of donation. Pooling available data from HCV non-viremic donors, including the single false-negative NAT case, there is an overall transmission rate of 1.1%. When donor viremia has been adequately excluded with HCV NAT testing, there have been no documented cases of transmission from non-viremic donors to HCV-naïve recipients. However the risk from viremic patients without DAA is almost 100% in HCV naïve patients.
· Will you accept this donor as a live donor if the recipient is also HCV.
Yes, it will be more easier provided that it is same genotype or genotype group.
· Assuming HCV PCR is not available, how would you manage the case?
It will be difficult to take decision in such situation. However if the recipient is in need for urgent transplantation, I may consider it after explanation of the risk of transmission and the unavailable data.
References:
1-Expanding the Deceased Donor Pool in Manitoba Using Hepatitis C-Viremic Donors: Program Report, Canadian Journal of Kidney Health and Disease Volume 8: 1–10
Thanks, acknowledged
What is the chance of transmission of HCV in HCV antibody positive, HCV PCR negative?
56-year-old, man
DBD donor
Virology
Will you accept this DBD donor?
Yes, I would accept this donor. HCV Ab + with NAT -ve (not viremic) indicated that virus clearance spontaneously or with treatments (no active infection).In other words, is no current hepatitis C (1). However, this could be due to false positive results. Overall the transmission risk is very low (2)
Will you accept this donor as a live donor if the recipient is HCV-positive? If yes, what are the conditions that should be met?
Yes, provided there is access to DAA therapy post-transplantation, and the donor has no evidence of cirrhotic liver.
Assuming HCV PCR is not available, how would you manage the case?
Reference
Thanks, acknowledged
Thank you All. I’ve noticed a few of you who referred to the recently published KDIGO guidelines for hepatitis C in CKD.
It states the following:
‘ 4.2.3: We recommend that kidneys from HCVinfected donors be considered regardless of HCV status of potential kidney transplant recipients (1C).
The most important points here are:
1- Recipient counselling, discussions, education for an informed consent
2- Recipient should be treated promptly after transplantation for 12 weeks with excellent patient and graft survival and excellent SVR12.
Clearly in our scenario treatment post transplant is not mandatory as donor was HCV antibody only positive
My approach in this case would probably wait for HCV PCR result which will confirm donor infectivity and to know the gene type of the virus and if this is negative no need for treatment with a recheck of HCV after 12 weeks post transplantation to ensure no risk of viral transmission.
In the unlikely event of difficulty getting HCV PCR result for any reason, then will use DAA empirically for 12 weeks with lack of virus genotype with risk of suboptimal treatment response.
Dear Sir,
In this scenario given, HCV PCR results are not available (HCV Ab positive) upon transplantation, we proceed with transplantation (after counselling the risk and benefit) and trace back the NAT and the genotype retrospectively before initiating treatment?
Thanks, Maisara
See the scenario, HCV PCR is negative.
👉 Yes I will accept this donor (postive anti HCV Antibody and negative PCR), as this means clearance from infection either spontaneously or with treatment 👉 although the risk of transmission in the index case is very low, Follow up of the recipient by PCR is essential to detect presence of any viremia (if tested positive at any time, early treatment is indicated with GZR/EBR for 12 weeks till achieving SVR.
👉 If the is alive donor, I can accept the donor for HCV postive recipient (with the following precautions)
⭐ After making sure that no evidence of HCV associated nephropathy (cryoglobulinemia, MN or MPGN) as this can be associated with recurrent or Denovo disease in the allograft (urinalysis showing hematuria/protinuria).
⭐ The donor has no advanced cirrhosis by liver biopsy, ultrasound and fibroscan).
⭐ The recipient has no evidence of advanced cirrhosis that can require combined liver and kidney transplant ion.
⭐ Treatment of both the donor and the recipient either pretransplant (if no urgency for transplantation now) or starting after transplantation.
👉 If no available PCR, deal with the donor as HCV postive with counseling of the recipient about the risk of viremia post transplant, the need for frequent PCR monitoring and starting early ttt once postive PCR.
Ø Yes accepted for donation
Ø HCV positive antibody indicate previous infections .
Ø Hepatitis C Ab+ donors should be defined by NAT testing as non-viremic (NAT−) versus viremic (NAT+) Hepatitis C Ab+/NAT− kidneys can be transplanted safely into HCV− recipients
Ø Post-transplant NAT testing is recommended to confirm lack of disease
Ø HCV− recipients transmission; if de novo HCV infection occurs, DAAs should be rapidly instituted
Ø Hepatitis C Ab+/NAT− kidneys can be transplanted into HCV NAT+ recipients,DAA treatment should begin post-transplant
Ø Transplantation with HCV NAT+ kidneys into HCV NAT+ recipients is recommended
Ø Post-transplant DAA treatment should be started
Transplantation with HCV NAT+ kidneys into HCV− recipients with DAA treatment is possible
Ø KDIGO : HCV− recipients of HCV NAT+ organs should be followed closely to capture potential complications
References :
1. Kidney Disease Improving Global Outcomes KDIGO clinical practice guidelines for the prevention, diagnosis, evaluation and treatment of hepatitis c in chronic kidney disease. Kidney Int 2008; 73(suppl 109): S1–S99.
2. Sawinski D, Bloom RD. Novel hepatitis C treatment and the impact on kidney transplantation. Transplantation. 2015:1–9.
3- Fabrizi F, Cerutti R, Alfieri CM, Mesa P. Updated view on kidney transplant from HCV-infected donors and DAAs. Pharmaceutics. 2021;13:496.
well done
Will you accept this DBD donor?
Yes, I will accept this potential donor:
· Positive anti-HCV antibody may reflect neutralization and immunity after clearance of previous HCV infection.
· It is well recommended by KDIGO that all kidney transplant candidates with HCV be considered for DAA therapy, either before or after transplantation (1).
· It is recommended by KDIGO that kidneys from HCV-infected donors be considered regardless of HCV status of potential kidney transplant recipients (1).
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Yes, I will accept: donation from HCV-infected donor is acceptable and have to be considered regardless of HCV status of the KTR as stated by KDIGO guidelines.
Conditions that should be met are:
1. Donors do not have cirrhosis.
2. Donors should undergo HCV treatment before donation if the recipient is HCV-uninfected; they can be accepted for donation if they achieve sustained virologic response (SVR) and remain otherwise eligible to be a donor(1).
Assuming HCV PCR is not available, how would you manage the case?
In the setting of unavailability of HCV PCR, I will consider the donor positive PCR for HCV. In such situation, I will initiate DAAs in the early post-transplant period. HCV PCR to be checked in the post-transplant period at day3-day7 – day10 -day14 and 6weeks post-transplant.
· Transplantation of HCV-viremic organs into HCV-naive recipients followed by the use of DAA agents provides excellent patient and allograft survival(2).
· Securing DAA therapy post-transplant is essential and patients should be fully informed of the associated risks, including the potential of HCV treatment failure(2).
References
1. KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease VOLUME 102 | ISSUE 6S | DECEMBER 2022 http://www.kidney-international.org
2. Patnaik R, Tsai E. Hepatitis C Virus Treatment and Solid Organ Transplantation. Gastroenterol Hepatol (N Y). 2022 Feb;18(2):85-94. PMID: 35505819; PMCID: PMC9053510.
Excellent
?Will you accept this DBD donor
Yes . This deceased donor has either treated or cleared HCV infection; there is low risk of transmission so I will proceed for transplantation .
? positive .If yes, what are the conditions that should be met .
For the recipient :
: Reference
Kidney Int. 2022 Dec;102(6):1228-1237. doi: 10.1016/j.kint.2022.07.012.
Executive Summary of the KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease
Will you accept this DBD donor?
Yes.
In this HCV antibody is positive but HCV PCR is negative. HCV positive antibody and negative PCR can be due to previous treatment, spontaneous clearance ,false positivity or low viral load, . There is no contraindication for donation.
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Yes I will accept . Criteria for HCV positive donation to HCV Positive recipient include-
Absent cirrhosis and HCC in both
Rule out CKD in donor
Available DAA for both donor and recipient
Informed consent
Negative PCR
Treatment of donor pre donation with sustained virologic response
Planned follow up
Assuming HCV PCR is not available, how would you manage the case?
I will proceed with transplantation but will monitor him post transplant. If he becomes HCV positive then I will start direct antiviral therapy.
Patnaik R, Tsai E. Hepatitis C Virus Treatment and Solid Organ Transplantation. Gastroenterol Hepatol (N Y). 2022 Feb;18(2):85-94.
Will you accept this DBD donor?
Yes HCV Ab positive and HCV RNA negative indicates absence of active HCV infection
Additional tests to determine whether the initial positive HCV antibody represents clearance of a previous infection or a false‐positive test result can be considered, repeat HCV antibody testing using an approved HCV antibody assay
In this case the risk is small of HCV being transmitted to the recipient.
Meanwhile the DAAs presence curing HCV infection after transplant increased the acceptance of HCV+ kidneys also due to survival benefit associated with transplantation than remaining on the waiting list.
Standardized testing for HCV RNA of the recipient after receiving a HCV Ab positive graft to attain an early and appropriate intervention if HCV transmission and infection occurs.
f HCV PCR is positive after confirmatory results DAA to be started within 3-10 working days since the first positive test.
There are 2 regimens including combination of Glecaprevir/Pibrenatasvir or the combination of Sofosbuvir/Velpatasvir, both given for 12 weeks
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Yes, pending full evaluation of the severity of their liver disease of donor and recipient. NAT to confirm SVR durability in cases in patients who received antiviral treatment prior to waitlisting and obtaining SVR.
Assuming HCV PCR is not available, how would you manage the case?
Enzyme immunoassay can be done if NAT is not available
Short course of DAAT regimen can be given and SVR assessed
Reference
–Bowring MG, Kucirka LM, Massie AB, et al. Changes in Utilization and Discard of HCV Antibody-Positive Deceased Donor Kidneys in the Era of Direct-Acting Antiviral Therapy. Transplantation. 2018;102(12):2088-2095.
-Summa KC, Maddur H. Hepatitis C Antibody Positive, RNA Negative. Clin Liver Dis (Hoboken). 2019;14(1):5-7. Published 2019 Aug 2.
– Kidney Disease: Improving Global Outcomes. KDIGO clinical practice guidelines for the
prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease.
Kidney Int. 2008; 73 (suppl 109):S1–S99
56 ys old DBD, SAH, normal s.cr on retrieval, HIV, HBsAg -ve, HCV ab positive with negative PCR.
Yes, I will. No contraindications.
Yes, I will.
– Causes of HCV ab positive with PCR negative:
1- Infection with Low undetected viral load.
2- Treated infection.
3- No infection; False positive test, recent blood transfusion with anti-HCV positive ab.
– So, the status here will be either HCV-infected donor to HCV-infected recipient or HCV-non-infected donor to HCV-infected recipient, in both conditions, I will accept as a live donor.
– MDT management with a hepatologist to asses:
1- Need for simultaneous liver & kidney transplant if decompensated liver D or portal HTN>10 mmHg.
2- Option of pre-transplant treatment, otherwise could be treated post-transplant.
– NAT is more sensitive & specific in detecting if sensitivity or viremia, to classify the risk of transmission, but if also not available, I will consider him as HCV infected.
– So, if the recipient also is HCV positive, will proceed for transplantation with post-transplant treatment with DAA.
– If the recipient is negative, will proceed for transplantation if no available HCV-negative donors, or need for urgent transplantation like vascular access failure or a long time on the waiting list with informing & consenting the recipient.
– THINKER trial shows good outcomes in transplanting HCV -ve donors from HCV +ve.
– AS PER BTS recommendations:
– Recipient will be tested for PCR HCV on day 3- 7 & If negative The test is repeated in day 10-14 post-transplantation & If negative again The test is repeated in 6 weeks post-transplant .
– DAA started 3 to 10 days after any positive result of PCR HCV
Will you accept this DBD donor?
Yes I will accept this donor
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Yes I will accept this as donor after fulfiling following conditions.
Assuming HCV PCR is not available, how would you manage the case?
I will go ahead for transplantation but will start DAA as per the post transplant regeimn protocol, giving benefit to recipient and considering that DBD donor might be having some viral load.
REF:
Yes, I will accept with availability of DAA and comprehensive informed consent
This is a seropositive, nonviremic HCV infection and the risk of disease transmission is low. Possibilities of HCV Antibody+/HCV NAT- are:
1. spontaneous clearance of HCV
2. successful treatment of infection
3. false-positive antibody result
Anti-HCV antibody+/HCV RNA – should be tested for HCV RNA 12 and 24 weeks latter to confirm defitive clearance
KDIGO 2022: we recommend that kidneys from HCV-infected donor be considered regardless of HCV status of potential kidney transplant recipients (1C).
Recipient HCV PCR day 3-7, day 10-14, and 6 weeks post-transplant. If positive at any time start DAA therapy within 3-10 days of the first positive test after confirmatory test
Securing DAA therapy post-transplant is essential and patients should be fully informed of the associated risks, including the potential of HCV treatment failure
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Yes, I will accept
KDIGO 2022: we recommend kidney transplantation as the best therapeutic option for patients with CKD-G5 irrespective of presence of HCV infection (1A)
Management of the recipient:
Evaluate for severity of liver disease and presence of portal hypertension:
1. Compensated cirrhosis and no portal hypertension: isolated kidney transplantation
2. Decompensated cirrhosis or clinically significant portal hypertension (hepatic venous gradient pressure 10 or more or evidence of portal hypertension on imaging or exam): simultaneous liver kidney transplantation
3. Mild to moderate portal hypertension treatment should be determined on a case-by-case basis
Timing of HCV treatment in relation to kidney transplantation (before vs. after):
Generally based on
1. donor type (living vs. deceased)
2. wait-list times by donor types
3. center-specific policies governing the use of kidneys from HCV-infected deceased donors
4. severity of liver cirrhosis
5. candidate sensitization
6. patient preference
All kidney transplant candidates with HCV be considered for DDA therapy, either before or after transplantation (1A)
HCV-infected kidney transplant candidates with a living kidney donor be considered for treatment before or shortly after transplantation depending on the anticipated timing of transplantation (2B).
Maintenance of immunosuppressions:
Evaluate for the need for dose adjustment of immunosppressants in kidney transplant recipient treated with DAA
For F0 to compensated cirrhosis without portal hypertension:
o If living donor kidney transplantation is anticipated without a long wait (<24 weeks), treatment can be deferred until after transplantation (avoid drug-drug interaction peritransplant)
o If living donor kidney transplantation is likely to be delayed more than 24 weeks, HCV therapy can can be offered before or after transplantation (12 weeks for therapy and 12 weeks of follow-up to confirm SVR)
Combinations DAA used in post-transplant settings include glecaprevir-pibrentasvir, sofosbuvir-ledipasvir, sofosbuvirsimeprevir, sofosbuvir-daclatasvir and paritaprevirdasabuvir
Few DAA such as simeprevir and dasabuvir are associated with significant drug interaction with immunosuppressants. Close monitoring of the therapeutic drug level of calcineurin inhibitor is required with use of DAA in SOT
Correct factors associated with accelerated disease including alcohol use, obesity, insulin resistance and substance abuse
Hepatitis c infection after transplantation is associated:
1. liver disease
2. Recurrence or new onset of HCV related kidney disease (recurrent glomerular disease or de novo MPGN or MN, renal thrombotic microangiopathy). As HCV associated glomerular disease usually presents with progressive proteinuria, screen regularly for proteinuria and haematuria (every 6 months)
3. PTLD
4. NODAT
5. fibrosing cholestatic hepatitis: rare and characterized by cholestasis and progressive liver failure HCV associated kidney disease after transplant include
Assuming HCV PCR is not available, how would you manage the case?
HCV core antigen in serum or plasma is a marker of HCV replication and can be used instead of HCV RNA to diagnose acute or chronic HCV infection when HCV RNA is not available and/or not affordable
If both are not available, I will consider HCV RNA positive and proceed for transplantation
References
1. Kidney Disease: Improving Global Outcomes (KDIGO) Hepatitis C Work Group. KDIGO 202 2 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in ChronicKidney Disease. Kidney Int. 2022;102(6S):S129–S205.
2. Pantnaik R, Tsai E, Hepatitis C Virus Treatment and Solid Organ Transplantation. Gastroenterol Hepatol (NY). 2022 Feb;18(2):85-94. PMID:35505819; PMCID: PMC9053510.
3. UK Position Statement on the use of Organs from Hepatitis C Viraemic Donors and Increased Infectious Risk Donors in Hepatitis C Negative Recipients.
4. Sawinski D, et al. Renal transplantation using kidneys from hepatitis C-infected donors: A review of 30-years’ experience. Nefrologia. 2022.https://doi.org/10.1016/j.nefro.2022.04.005
5. Shenoy P, Buttigieg J, Zayan T, Sharma A & Halawa A. (2018) Infections after Solid Organ Transplantation. J Renal Transplant Sci, 1(1): 29-42.
6. EASL Recommendations on Treatment on Hepatitis C 2018.
The index patient is offered a kidney from a 56-year-old male DBD (donor after brainstem death) kidney with no evidence of Hepatitis B and HIV infection, and presence of anti-HCV antibodies and absent HCV RNA PCR.
The scenario implies either a false positive anti-HCV antibody, or a past infection which either got cleared spontaneously (in 5% cases), or after being treated.
The HCV status of the recipient has not been provided. Nevertheless, I will accept this donor in view of low-risk of transmission in absence of viremia, after counselling the recipient and HCV positive donors can be accepted regardless of the HCV status of the potential kidney transplant recipient (1).
Post-transplant, the recipient should be tested for HCV RNA PCR (2). The testing should be done on day 3-7, then on day 10-14, and then 6 weeks post-transplant. If the reports are negative even at 6 weeks, the recipient can be reassured. If the HCV PCR comes out positive during the testing in first 6 weeks, the patient should be treated with directly acting antivirals (DAAs) within 3-10 days (2).
In the scenario of a live donor who is anti-HCV antibody positive, donating to a recipient who is HCV positive, I will accept the donor after evaluating both the donor and the recipient. HCV positive donors can be accepted regardless of the HCV status of the potential kidney transplant recipient (1).
Recipient evaluation: The recipient should be evaluated with respect to positive HCV status – anti-HCV antibodies, HCV RNA PCR, hepatology consultation, Liver function tests, ultrasound abdomen, and assessment of liver fibrosis (elastography, liver biopsy) and portal hypertension (upper gastrointestinal endoscopy). In presence of advanced liver fibrosis, a combined liver and kidney transplant would be required.
Donor evaluation: The prospective donor should be evaluated with HCV nucleic acid testing (HCV-NAT), which if positive, would require hepatology consultation and evaluation of liver disease in form of liver function tests (LFT). The prospective donor should also be monitored for renal function, hematuria, and proteinuria (1).
The prospective living donor should be treated with DAA therapy. Living donation can be proceeded with in absence of severe hepatic fibrosis and renal disease. In case both the donor and recipient are HCV infected, the DAA treatment of the donor can be delayed (1). If the recipient is HCV-uninfected, then the donor should be treated pre-donation (1).
In the index scenario, as the live donor is HCV RNA PCR negative, no need of DAA treatment for the donor. If there is no hepatic or renal dysfunction, the donor can be accepted. As the recipient is HCV positive, the recipient evaluation should be done as enumerated above. If recipient HCV RNA PCR is positive, the recipient should be treated with DAAS. If there is urgency (poor vascular access, patient not tolerating dialysis), then the transplant can be proceeded with and the treatment of the recipient can be done post-transplant.
If the donor HCV PCR is not available, the transplant can be proceeded with. Post-transplant, the recipient should be tested for HCV RNA PCR (2). The testing should be done on day 3-7, then on day 10-14, and then 6 weeks post-transplant. If the reports are negative even at 6 weeks, the recipient can be reassured. If the HCV PCR comes out positive during the testing in first 6 weeks, the patient should be treated with directly acting antivirals (DAAs) within 3-10 days (2).
References:
Will you accept this DBD donor?
Potential donor has isolated HCV positive by serologic testing but NAT negative (nonviremic), which may result of the following:
– Spontaneous clearance or successful treatment of infection.
– False-positive antibody result.
– Recent blood transfusion with anti-HCV. ( antibodies will disappear over thenext few weeks in keeping with T1/2 of IgG)
– Vertical transmission in neonate.
– False-negative RNA test, unusual very low viral load.
Therefore, this donor can be accepted. As these donors have not been documented to transmit HCV infection, and outcome is good.
Recipients of HCV-seropositive/RNA-negative kidneys appear to have the same graft and patient survival as recipients of HCV-seronegative kidneys (1)
However, this recipient should be monitored with HCV PCR at day 3-7 Post-Tx, then day 10-14,then at 6 weeks if all results are negative reassure the recipient & managed as standard recipients. If HCV PCR positive; DAA started within 3-10 days of first positive PCR.
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Yes This donor can be accepted in the setting of LD, after careful evaluation, as the use of HCV RNA positive organs with early initiation of DAA is recently being acceptable.
Transplantation should be avoided in recipients with advanced fibrosis or cirrhosis.
Evaluation include:
– Liver function test.
– Liver US.
– Screening using AST-to-Platelet Ratio Index (APRI).
If the APRI score is >0.8 or the ultrasound suggests significant or advanced liver disease, then liver specialist opinion is recommended.
If the APRI score is <0.8, there is no need for the patient to be seen by a liver specialist.
– Liver biopsy may be required.
-Evaluate for extrahepatic manifestation: renal involvement with:
-Renal function.
-Urine analysis for proteinuria, hematuria.
Consider treatment for LD before transplantation if no urgent transplantation and after balancing risk and benefit.
Recipient with HCV PCR positive:
Evaluated the same way
If found to have advanced liver disease may benefit from combined liver-kidney transplantation.
Consider treating the recipient ( while waiting on the list) before transplantation to avoid drug-drug interaction if situation allows, and no urgent need for transplantation and donor will remain available after treatment course.
Assuming HCV PCR is not available, how would you manage the case?
We can proceed with transplantation if PCR is not available, it is saver to consider this donor as viremic with high transmission risk. Thus require frequent monitoring to ensure appropriate and early intervention if HCV transmission and infection occurs.
Testing donor HCV genotype.
Ensure the availability of HCV treatment.
Recipient monitored with HCV PCR at day 3-7 Post-Tx, then day 10-14,then at 6 weeks if all results are negative reassure the recipient & managed as standard recipients.
If recipient HCV PCR positive; DAA started within 3-10 days of first positive PCR.
However, we need to balance the benefit of transplantation and donor derived infection must be considered against the risk of not receiving the organ, continuing on dialysis, waitlist time and immunological risk.
References :
Fontaine H, Alric L, Labreuche J, Legendre B, Louvet A, Antoine C, Legendre CM, Hazzan M, Kamar N, Dharancy S, Pol S, Duhamel A, Mathurin P. Control of replication of hepatitis B and C virus improves patient and graft survival in kidney transplantation. J Hepatol. 2019 May;70(5):831-838. doi: 10.1016/j.jhep.2018.12.036. Epub 2019 Mar 14. PMID: 30879789.
Doherty DT, Athwal V, Moinuddin Z, et al. Kidney Transplantation From Hepatitis-C Viraemic Donors:Considerations for Practice in the United Kingdom. Transpl Int. 2022;35:10277. Published 2022 May 3. doi:10.3389/ti.2022.10277
The British Viral Hepatitis Group has recently issued a position statement on the use of organs from hepatitis C viraemic donors in hepatitis C negative recipients.
Dear All
Is it important to check urine for proteinuria and haematuria for donor who had HCV infection? Why?
Well done
It is important to rule out renal involvement that can be associated with HCV. That can be present with proteinuria, microscopic hematuria, hypertension, acute nephritis and nephrotic syndrome
Common glomerular lesions including: MPGN, Mixed cryoglobulinemia, Membranous nephropathy, PAN.
Crescentic glomerulonephritis may be superimposed on any of these glomerular lesions.
Less commonly glomerular lesions: FSGS, proliferative glomerulonephritis, and fibrillary and immunotactoid glomerulopathies.
Reference:
Ozkok A, Yildiz A. Hepatitis C virus associated glomerulopathies. World J Gastroenterol. 2014 Jun 28;20(24):7544-54. doi: 10.3748/wjg.v20.i24.7544. PMID: 24976695; PMCID: PMC4069286.
Johnson RJ, Willson R, Yamabe H, Couser W, Alpers CE, Wener MH, Davis C, Gretch DR. Renal manifestations of hepatitis C virus infection. Kidney Int. 1994 Nov;46(5):1255-63. doi: 10.1038/ki.1994.393. PMID: 7853784.
You referred to Crescentic glomerulonephritis, do you think with this lesion kidney function will be normal?
in crescentic GN kidney function will be abnormal and rapidly deteriorating.
as screening for membranoproliferative GN, as well as blood pressure monitoring
As screening for underlying glomerular pathology due to HCV is right but what did you mean by blood pressure monitoring?
Thank you prof.
HCV infection after transplantation is associated with recurrent or new onset HCV related kidney disease (recurrent glomerular disease or de novo MPGN or MN, renal thrombotic microangiopathy). As HCV associated glomerular disease usually present with progressive proteinuria, sceen regularly for proteinuria and haematuria.
Reference
1. Shenoy P, et al. (2018) Infections After Solid Organ Transplantation. J Renal Transplant Sci, 1(1): 29-42.
Have you read the question carefully? It’s about the donor urine analysis to check suitability to donate a kidney in the context of previous history of HCV?
Sorry
Cryoglobulinemia and other forms of HCV-associated glomerulonephritis (MPGN, membraneous nephropathy, and others)
To evaluate for HCV associated nephropathies like
MPGN
FSGS
IgAN
Fibrillary glomerulopathy
Thank you
Yes as chronic HCV infection can be associated with many glomerular diseases including mixed cryoglobulinemia with MPGN-like nephropathy and membranous nephropathy, Ig A nephropathy, and FSGS as well and chronic hepatitis screen is part of proteinuria in general and in HCV related need to send C3, C4 urine p/c ratio, and cryoglobulin level and kidney biopsy
It would be better to refer to what type of donor you are discussing live or cadaveric?
to r/o renal involvement, mostly MPGN pattern, cryoglobulinemia with crescentic GN can be presented as RPGN.
I’m still warry about crescentic GN in kidney donor. This will probably be excluded from the outset because of impaired kidney function.
sure, sir. In crescentic GN, the patient will present with a rapidly deteriorating kidney injury.
Thnxs prof, yes HCV is associated with a wide range of glomerular diseases such:
Thank you
Welcome prof Mohsen
HCV associated nephropathies should be excluded or diagnosed if present like mixed cryoglobulinemia, systemic vasculitis, MPGN, MGN, FSGS,fibrillary GN
Andrea Angeletti,Chiara Cantarelli, Paolo Cravedi. HCV-Associated Nephropathies in the Era of Direct Acting Antiviral Agents. Sec. Nephrology. Volume 6 – 2019
Thanks, acknowledged
Yes it is important as to rule out HCV associated glomerular disease like MPGN ,Membraneous Nephropathy and also HCV related cryoglubilnemia
Thanks, acknowledged
Yes .Because of cryoglobulinemia is an extrahepatic presentation of HCV infection with a histological pattern of membranoproliferative glomerulonephritis.
Less frequent glomerulopathy include membranous nephropathy, focal segmental glomerulosclerosis, IgA nephropathy, fibrillary and immunotactoid glomerulopathy.
Reference
Angeletti A, Cantarelli C and Cravedi P (2019) HCV-Associated Nephropathies in the Era of Direct Acting Antiviral Agents. Front. Med. 6:20
Thanks, acknowledged
Hepatitis C virus (HCV) infection is a systemic disorder which is often associated with a number of extrahepatic manifestations including glomerulopathies. Patients with HCV infection were found to have a higher risk of end-stage renal disease. HCV positivity has also been linked to lower graft and patient survivals after kidney transplantation. Various histological types of renal diseases are reported in association with HCV infection including membranoproliferative glomerulonephritis (MPGN), membranous nephropathy, focal segmental glomerulosclerosis, fibrillary glomerulonephritis, immunotactoid glomerulopathy, IgA nephropathy, renal thrombotic microangiopathy, vasculitic renal involvement and interstitial nephritis. The most common type of HCV associated glomerulopathy is type I MPGN associated with type II mixed cryoglobulinemia. Clinically, typical renal manifestations in HCV-infected patients include proteinuria, microscopic hematuria, hypertension, acute nephritis and nephrotic syndrome. Three approaches may be suggested for the treatment of HCV-associated glomerulopathies and cryoglobulinemic renal disease: (1) antiviral therapy to prevent the further direct damage of HCV on kidneys and synthesis of immune-complexes; (2) B-cell depletion therapy to prevent formation of immune-complexes and cryoglobulins; and (3) nonspecific immunosuppressive therapy targeting inflammatory cells to prevent the synthesis of immune-complexes and to treat cryoglobulin associated vasculitis. In patients with moderate proteinuria and stable renal functions, anti-HCV therapy is advised to be started as pegylated interferon-α plus ribavirin. However in patients with nephrotic-range proteinuria and/or progressive kidney injury and other serious extra-renal manifestations, immunosuppressive therapy with cyclophosphamide, rituximab, steroid pulses and plasmapheresis should be administrated(1).
Reference
1. Ozkok A, Yildiz A. Hepatitis C virus associated glomerulopathies. World J Gastroenterol. 2014 Jun 28;20(24):7544-54. doi: 10.3748/wjg.v20.i24.7544. PMID: 24976695; PMCID: PMC4069286.
Thanks, acknowledged
Is it important to check urine for proteinuria and haematuria for donor who had HCV infection? Why?
Dear Dr Ahmed,
The answer is yes; chronic viral infection is associated with a higher risk of developing variable forms of glomerular kidney disease (e.g. MPGN, Cryoglobulinemia and other forms of glomerulonephritis), as illustrated in the attached table (1).
References:
1) Steddon S, Ashman N, Chesser A, et al. Oxford Handbook of Nephrology and Hypertension. Second edition, Oxford University Press, ISBN 978–0–19–965161–0, 2014.
_Yes, to exclude HCV associated glomerular diseases as (cryoglobulinemia, membranous nephropathy and MPGN) that can be presented with microscopic hematuria, variable degrees of protinuria, nephritis or even nephrotic syndrome.
in addition, blood pressure monitoring is important.
Hepatitis C virus (HCV) infection is a systemic disorder associated with a number of extrahepatic manifestations including glomerulopathies
Histological types of renal diseases are association with HCV infection including :
Membranoproliferative glomerulonephritis (MPGN), Membranous nephropathy
Focal segmental glomerulosclerosis
Fibrillary glomerulonephritis,
Immunotactoid glomerulopathy
IgA nephropathy,
Renal thrombotic microangiopathy,
Vasculitic renal involvement
Interstitial nephritis.
The most common type of HCV associated glomerulopathy is type I MPGN associated with type II mixed cryoglobulinemia
Clinically, in HCV-infected patients include proteinuria, microscopic hematuria, hypertension, acute nephritis and nephrotic syndrome
The treatment of HCV-associated glomerulopathies and cryoglobulinemic renal disease:
(1) antiviral therapy to prevent the further direct damage of HCV on kidneys and synthesis of immune-complexes; (2) B-cell depletion therapy to prevent formation of immune-complexes and cryoglobulins.
(3) nonspecific immunosuppressive therapy targeting inflammatory cells to prevent the synthesis of immune-complexes and to treat cryoglobulin associated vasculitis
serious extra-renal manifestations, immunosuppressive therapy with cyclophosphamide, rituximab, steroid pulses and plasmapheresis should be administrated.
REFERNCE:
1. Cacoub P, Renou C, Rosenthal E, Cohen P, Loury I, Loustaud-Ratti V, Yamamoto AM, Camproux AC, Hausfater P, Musset L, et al. Extrahepatic manifestations associated with hepatitis C virus infection. A prospective multicenter study of 321 patients. The GERMIVIC. Groupe d’Etude et de Recherche en Medecine Interne et Maladies Infectieuses sur le Virus de l’Hepatite C. Medicine (Baltimore) 2000;79:47–56. [PubMed] [Google Scholar]
Is it important to check urine for proteinuria and haematuria for donor who had HCV infection? Why?
Yes. It is important to have a urine analysis of the prospective donor to look for hematuria/ proteinuria to rule out any glomerular disease which could be HCV related or unrelated to HCV infection. These include cryoglobulinemic MPGN, membranous nephropathy, or FSGS (1).
Reference:
Thanks, our Prof,
Yes, it is important to check urine for the donor with HCV + infection
because the effect of HCV on kidney in the form of;
MPGN, Cryoglobulinemia ,FSGS, IgAN , Membranous nephropathy ,Fibrillary GN , Immunotactoid GN , Diabetic nephropathy.
Yes it is important to check urine for proteinuria and hematuria. This is because patient with HCV infection are at risk of developing some glomerulonephrits like:
1-Cryoglobuinemia, MPGN type 1.
2-Membranous nephropathy.
3-FSGS
4-Ig A nephropathy
5-Immunotactoid glomerulopathy
6-Interstitial nephritis
7-TMA
8-Renal vasculitis
References:
World Journal of gastro entrology 2014, 28; 20(24) 7544-7554
Membranoproliferative GN
To exclude secondary glomerulonephritis due to HCV
Yes, to exclude underlying GN
membranoproliferative glomerulonephritis (MPGN), membranous nephropathy, focal segmental glomerulosclerosis, fibrillary glomerulonephritis, immunotactoid glomerulopathy, IgA nephropathy, renal thrombotic microangiopathy, vasculitic renal involvement,, and interstitial nephritis. The most common type of HCV-associated glomerulopathy is a type I MPGN associated with type II mixed cryoglobulinemia. Clinically, typical renal manifestations in HCV-infected patients include proteinuria, microscopic hematuria, hypertension, acute nephritis, and nephrotic syndrome.
Because some patients develop glomerulonephritis related to hepatitis C like Poly arthritis nodusm and cryoglobulinemia
Renal manifestations in HCV-infected patients include proteinuria, microscopic hematuria, hypertension and nephrotic syndrome. Often patients have impaired renal fuction. The most common type of HCV associated glomerulopathy is MPGN associated with type II mixed cryoglobulinemia.
Other histological types of renal diseases reported in association with HCV infection include:
Reference:
Habas E Sr, Farfar KL, Errayes N, Habas AM, Errayes M, Alfitori G, Rayani A, Elgara M, Al Adab AH, Elzouki A. Hepatitis Virus C-associated Nephropathy: A Review and Update. Cureus. 2022 Jul 27;14(7):e27322. doi: 10.7759/cureus.27322. PMID: 36043014; PMCID: PMC9412079.
To check for cryoglobulinemia since this is a typical extra hepatic manifestation of HCV infection. Cryoglobulinemia involves the kidneys and has a histological pattern of membranous glomerulonephritis.
Other less common renal diseases linked to HCV infection include membranous nephropathy, focal segmental glomerulosclerosis, IgA nephropathy, fibrillary and immunotactoid glomerulopathy.
Typically, clinical manifestations include proteinuria, microscopic hematuria, hypertension, acute nephritis and nephrotic syndrome.
References :
This is to screen for other HCV associated nephropathies i.e membranous, immunotactoid GN,IGA nephropathy, FSGS, Cryoglobulinemic GN
REF;
Andrea et al ;HCV associated Nephropathies in the era of DAA therapy. Front med, vol 6-2019
Is it important to check urine for proteinuria and haematuria for donor who had HCV infection? Why? (1, 2)
– yes, it is important to check urine for proteinuria and hematuria
– chronic HCV infection can cause different forms of kidney disease hence the need to monitor proteinuria and hematuria
– the most common renal manifestations of HCV infection are:
– MPGN is most commonly associated with HCV infection
– other glomerulonephritides associated with HCV include:
References
1. Latt N, Alachkar N, Gurakar A. Hepatitis C virus and its renal manifestations: a review and update. Gastroenterology & hepatology. 2012 Jul;8(7):434-45. PubMed PMID: 23293553. Pubmed Central PMCID: PMC3533219. Epub 2013/01/08. eng.
2. Markowitz GS, Cheng JT, Colvin RB, Trebbin WM, D’Agati VD. Hepatitis C viral infection is associated with fibrillary glomerulonephritis and immunotactoid glomerulopathy. Journal of the American Society of Nephrology : JASN. 1998 Dec;9(12):2244-52. PubMed PMID: 9848778. Epub 1998/12/16. eng.
Yes it is because HCV can cause MPGN(due to chronic antigenmia), MN and cryoglobulinemia
Its important , as it might indicate glomerular disease secondary to previous HCV infection, Common glomerular disease is membrano proliferative GN and FSGS. Presence of proteinuria and hematuria is warranting further investigation with kidney biopsy , with higher chance of refusal.of the donor.
Will you accept this DBD donor?
History
A 56-year-old male DBD donor with HBsAg negative, HBsAb negative, HBcAb negative, HBeAg negative, HCV antibody positive, HCV PCR negative, HIV negative.
Will you accept this donor as a live donor if the recipient is also HCV positive?
conditions that should be met in above case.
In the absence of a living donor the two options would be: –
Assuming HCV PCR is not available, how would you manage?
In the absence of PCR, we should consider him positive.
It is advised to begin antiviral medication prior to kidney donation for chronic HCV carriers in circumstances where living donors have HCV infection or where PCR is not available.
Most HCV infections can be treated with short (8–12 week) DAA regimens. Sustained virologic response (SVR) after 12 weeks suggests an HCV cure.
Reference
Thank you for your reply. This is a picture of a patient who was treated or cleared the HCV. The HCV antibodies indicated past infection. We need to make sure that there is no HCV-associated nephritis.
Yes, for a living donor, I will exclude liver disease also. Well done. This is a model answer.
Will you accept this DBD donor?
Regardless of recipients’ HCV status, HCV-infected donor kidneys are recommended. Hence, I will accept the patient.
Transplant centers must educate and inform patients before transplanting HCV-infected kidneys into HCV-uninfected recipients. Patients should understand the risks and benefits of HCV-infected kidney transplantation, including DAA treatment.
When transplanting kidneys from HCV-infected donors to HCV-uninfected recipients, transplant centers should confirm DAA availability for early post-transplantation.
Will you accept this donor as a live donor if the recipient is also HCV-positive? If yes, what are the conditions that should be met?
If the recipient is HCV-uninfected, HCV-infected potential living kidney donors who do not have cirrhosis should receive HCV treatment before donation. If they achieve sustained virologic response, no hepatic or extra-hepatic manifestations, and remain otherwise eligible to be a donor, they can be accepted for donation.
If the recipient is also HCV-positive then the approach is different. However, donation is still accepted. According to studies, receiving kidney transplants from HCV-positive donors does not result in an increase in the morbidity or death of the recipients who are HCV-positive.
Laboratory and imaging examinations should be carried out in order to assess the recipient’s liver’s current condition; nevertheless, a liver biopsy is required for confirmation if the results are inconclusive or raise a high suspicion of cirrhosis.
Assuming HCV PCR is not available, how would you manage the case?
In the absence of PCR, we should consider him positive.
It is advised to begin antiviral medication prior to kidney donation for chronic HCV carriers in circumstances where living donors have HCV infection or where PCR is not available. Most HCV infections can be treated with short (8–12 week) DAA regimens. Sustained virologic response (SVR) after 12 weeks suggests an HCV cure. Hence, this approach lessens the potential of HCV transmission to receivers with HCV RNA negative or superinfection with a different genotype among recipients with HCV RNA positive.
Thank you for your reply. This is a picture of a patient who was treated or cleared the HCV. The HCV antibodies indicated past infection. We need to make sure that there is no HCV-associated nephritis.
Yes, for a living donor, I will exclude liver disease also.
Yes I will accept this donor with hepatitis C Abs positive and HCV PCR negative
presence of hepatitis c Abs either false report or prior infection has been resolved
if there are risk factors for hepatitis c or HCV exposure within the last 6 months for hepatitis c infection repeat HCV nucleic acid testing.
Thank you for your reply. This is a picture of a patient who was treated or cleared the HCV. The HCV antibodies indicated past infection. We need to make sure that there is no HCV-associated nephritis.
Yes, for a living donor, I will exclude liver disease also. Well done. This is a model answer.
Yes, this donor can be approved for donation after monitoring of HCV viral load frequent times, liver functions, and hepatology consultation is mandatory along with Fibroscan if requested to ensure the abolished risk of HCV transmission even by different genotype rather than the recipient.
Regarding the recipient being HCV positive antibody and nucleic acid testing by PCR suggests initiation of DAAs as soon as possible according to co-ordination between hepatology and transplant centre together ,after assessment of liver enzymes ,hepatic tissue by fibroscan to elaborate whether the patient may require simultaneous liver kidney transplantation or not.
Assuming HCV PCR is not available, management would be totally depending on close frequent monitoring of HCV status in the recipient after transplantation ,without any delay in performing renal transplantation as the risk of remaining on waiting list and dialysis is by far more hazardous than undergoing renal transplantation ,this also requires counselling the recipient and obtaining a consent , along with checking the insurance system for the availability of DAAs if the recipient converted into HCV seropositive and needed treatment .
Another option after consenting the recipient is to initiate the DAA therapy and ezetimibe prior to renal transplantation in a prophylactic protocol for the perioperative period up to 7 days before discharge to home.
(KDIGO guideline) TREATMENT OF HCV IN KIDNEY TRANSPLANT RECIPIENTS
https://kdigo.org/wp-content/uploads/2019/01/5.-Chow-KDIGO-hepatitis-C-Summit_renal-transplant.
Thank you for your reply. This is a picture of a patient who was treated or cleared the HCV. The HCV antibodies indicated past infection. We need to make sure that there is no HCV-associated nephritis.
Yes, for a living donor, I will exclude liver disease also.
A 56-year-old male DBD donor had Sr. Cr 78 µmol/L ====>
HBsAg, HBsAb, HBcAb, HBeAg, HBeAb ==> -ve
HIV (negative)
HCVAb (positive), HCV PCR (negative)==> may be ==> No active HCV infection , or cleared or treated HCV infection, or false-positive antibody.
Will you accept this DBD donor?
Yes, I will accept this DBD donor, as donor is HCV PCR negative, but antibody positive, which means there is no active HCV infection or replication.
Our Center Protocol (MAVIRET) (Glecaprevir / Pibrentasvir) and Ezetimibe
We are given Maviret(3 tablets) and Ezetimibe 10 mg ==> one dose pre-op then same dose for seven days ==> Ensure post-op dose is given within 24 HR from pre-op dose
HCV-positive donors may experience worse graft outcomes than recipients of transplants from HCV-negative donors.
Patients should be advised about the advantages and hazards of receiving an HCV-infected kidney transplant, also regarding the requirement for DAA therapy.
The recipient just needs to be counselled regarding the past HCV infection in the donor.
Treating HCV infection before transplantation may reduce the risk of HCV-associated renal dysfunction and progression.
Finally, very low risk of transmission of HCV from an antibody-positive, PCR-negative.
KDIGO-2022 guidelines:
Kidney transplantation is the best therapeutic option for patients with CKD G5 irrespective of presence of HCV infection. (1A)
After assessment of liver fibrosis, HCV-infected potential living kidney donors who do not have cirrhosis should undergo HCV treatment before donation if the recipient is HCV-uninfected; they can be accepted for donation if they achieve sustained virologic response (SVR) and remain otherwise eligible to be a donor. (Not Graded)
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Yes, I will accept the HCV positive live donor for HCV negative recipient.
BTS guidelines suggest that a course of therapy to cure a R- patient receiving a D+ organ would be less than the cost of dialysis for one year.
HCV D+/R- transplantation followed by early DAA therapy would result in only a transient, usually rapidly curable infection.
The donor needs to undergo AST-to-Platelet Ratio Index (APRI) and ultrasound done.
If the APRI score is >0.8 or the ultrasound suggests significant or advanced liver disease, then an opinion from a suitably qualified liver specialist should be sought.
D+/R- recipient should undergo HCV RNA at 1 week, 2 weeks and 6 months.
Whenever the PCR is positive, then the recipient needs to start DAA therapy within 3-10 days of the first positive PCR.
Proper consent of recipient is needed regarding all the complications and risk of HCV transmission and small risk of drug resistance HCV disease in recipient.
KDIGO-2022 GUIDLINES:
All kidney transplant candidates with HCV be evaluated for severity of liver disease and presence of portal hypertension prior to acceptance for kidney transplantation. (2D)
Patients with HCV, compensated cirrhosis and no portal hypertension undergo isolated kidney transplantation while patients with decompensated cirrhosis or clinically significant portal hypertension (i.e., hepatic venous pressure gradient ≥10 mm Hg or evidence of portal hypertension on imaging or exam) undergo a simultaneous liver-kidney transplantation. (1B) ,Those with mild-to-moderate portal hypertension should be determined on a case-by-case basis.
Referring patients with HCV and decompensated cirrhosis for combined liver-kidney transplantation. (1B)
Timing of HCV treatment in relation to kidney transplantation (before vs. after) should be based on donor type (living vs. deceased donor), waitlist times by donor type, center-specific policies governing the use of kidneys from HCV-infected deceased donors, and severity of liver fibrosis. (Not Graded)
All kidney transplant candidates with HCV be considered for DAA therapy, either before or after transplantation. (1A)
HCV-infected kidney transplant candidates with a living kidney donor be considered for treatment before or shortly after transplantation depending on the anticipated timing of transplantation. (2B)
Kidney transplant recipients being treated with DAAs be evaluated for the need for dose adjustments of concomitant immunosuppressants. (1C)
HCV-infected kidney transplant recipients should be tested at least every 6 months for proteinuria. (Not Graded)
Assuming HCV PCR is not available, how would you manage the case?
I Will accept the donor with HCV antibody positive and will consider him as HCV positive.
I will start peri operative DAA and would monitor him closely with PCR in the follow-up.
HCV positive donor, if the time to transplant is >24 weeks, I will treat the liver donor with
DAA and document SVR before transplant.
KDIGO-2022 GUIDLINE:
All kidney donors be screened for HCV infection with both immunoassay and NAT (if NAT is available). (1A)
Patients previously infected with HCV who achieved SVR before transplantation undergo testing by NAT 3 months after transplantation or if liver dysfunction occurs. (2D)
REFRENCESS:
Lecture of Professor May Hassaballah in HCV and kidney transplant
KDIGO-2022 guidelines
European Best Practice Guidelines for Renal Transplantation. Section I: Evaluation, selection and preparation of the potential recipient. Nephrol Dial Transplant 2000, 15 (suppl 7): 3-38.
Potluri VS, Goldberg DS, Mohan S, et al. National Trends in Utilization and 1-Year Outcomes with Transplantation of HCV-Viremic Kidneys. J Am Soc Nephrol 2019; 30: 1939-1951.
Ronit Patnaik, MD, Eugenia Tsai. Hepatitis C Virus Treatment and Solid Organ Transplantation. Gastroenterology & Hepatology Volume 18, Issue 2 February 2022.
UK Position Statement on the use of Organs from Hepatitis C Viraemic Donors and Increased Infectious Risk Donors in Hepatitis C Negative Recipients
Our Center Protocol (MAVIRET) (Glecaprevir / Pibrentasvir) and Ezetimibe
We are given Maviret(3 tablets) and Ezetimibe 10 mg ==> one dose pre-op then same dose for seven days ==> Ensure post-op dose is given within 24 HR from pre-op dose
Thank you for your reply. Will you give Maviret to this case?Why?
yes i accept after proper counseling / KTx is associated with better overall survival regardless of HCV status, this scenario low risk may be due to old or treated infection, passive Ab due to blood transfusion ( require history of any blood transfusion ), false positive,…etc
For living donor with HCV positive…….if time allow better to treat the donor then transplantation while if recipient already positive…. Yes you can accept with treating recipient with different protocols either before or after transplantation
in HCV positive recipient it is crucial to consult with hepatobiliary physian regarding the liver status , whether the patient need combined liver/ kidney transplantation or kidney transplantation alone
Thank you for your reply. This is a picture of a patient who was treated or cleared the HCV. The HCV antibodies indicated past infection. We need to make sure that there is no HCV-associated nephritis.
Yes, for a living donor, I will exclude liver disease also.
Yes I would accept this DBD donor. HCV Ab positive with a negative HCV PCR suggests:
If this was a live donor and the recipient is HCV positive
Yes, I would accept this donor
A hepatologist should be consulted
The recipient should be assessed for cirrhosis – whether compensated or decompensated and the hepatic venous pressure gradient (HVPG). If the patient has decompensated liver cirrhosis and/or HVPG of more than 10 mmHg, then he should be considered for both liver/kidney transplant. The decision should also be made as to when to treat the recipient – pre-transplant or post-transplant. The HCV genotype should be determined. If the patient does not have rapidly progressive cirrhosis, then he can be treated post-transplant, thereby reducing his waiting time. If he has rapidly progressive cirrhosis, he should be treated pre-transplant.
The problem with post-transplant treatment is that it can sometimes delay treatment due to getting approval from the insurance
Assuming HCV PCR was not available:
This would raise an ethical dilemma as one would not be sure if the patient has HCV infection
In this case the organ, if possible should go someone who is HCV positive so that the recipient can receive treatment with the directly acting antiviral agents
If there is no HCV positive recipient, then the potential recipient should be counseled before the transplant. After the transplant, frequent monitoring of the HCV PCR should be carried out – after one week, 2 weeks then at six weeks. If the HCV RNA is positive, DAA should be started immediately
Kidney International (2022) 102 (Suppl 6S), S129–S205
Thank you for your reply. This is a picture of a patient who was treated or cleared the HCV. The HCV antibodies indicated past infection. We need to make sure that there is no HCV-associated nephritis.
Yes, for a living donor, I will exclude liver disease also.
Will you accept this DBD donor?
The possibility of anti HCV+ve /PCR –ve can be:
· Previous HCV infection
· False positive
· Previously treated HCV
Yes, I will accept this patient kidneys, because of low risk of trasmitting hepatitis C virus infection in the recipient from anti HCV+/PCR- donors.
The recipient should be screened as follow: do HCV PCR at 3-7 days post Tx, repeated by day 10-14, then by 6 weeks post-transplant, if negative reassurance and no need for DAA therapy, if positive at any stage of screening, then start DAA within 3-10 days of positive test for 12 weeks, and confirm sustained viral response.
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Yes, I will accept this donor as a live donor to an HCV positive recipient.
Need to do HVC PCR, LFT , coagulation profile
Hepatologist evaluation of both donor and recipient for portal hypertension, and assessment of hepatic fibrosis (fibro scan or biopsy), If the potential recipient is having advanced liver fibrosis, then need to go for simultaneous liver kidney transplantation.
I would start DAA for both donor and recipient before transplantation, if time allowed before transplant, and achieving HCV cure, before kidney donation.
Assuming HCV PCR is not available, how would you manage the case?
If HCV PCR is not available will consider the donor as HCV Positive would go ahead for transplantation, with frequent monitoring of HCV PCR
Do HCV PCR at 3-7 days post Tx, repeated by day 10-14, then by 6 weeks post-transplant, if negative reassurance and no need for DAA therapy, if positive at any stage of screening, then start DAA within 3-10 days of positive test for 12 weeks, and confirm sustained viral response.
Reference
1.(KDIGO guideline) TREATMENT OF HCV IN KIDNEY TRANSPLANTRECIPIENTS
2- Position Statement on the use of Organs from Hepatitis C Viraemic Donors and Increased Infectious Risk Donors in Hepatitis C Negative Recipients(BTS)
Thank you for your reply. Well done Sumit.
This is a picture of a patient who was treated or cleared the HCV. The HCV antibodies indicated past infection. We need to make sure that there is no HCV-associated nephritis.
Yes, for a living donor, I will exclude liver disease also. Well done. This is a model answer.
Thank you Prof.
DBD Potential donor with anti HCV Ab +ve , but HCV PCR –ve, and negative HBV serology.
Causes of anti HCV+ve /PCR –ve :
· Low level of virus load to be detected < 25 copies.
· Previous HCV infection
· False positive – connective tissue disease example SLE
· ? Recent blood transfusion with anti HCV
· Drug abusers cleared HCV infection
· In babies of mothers with anti HCV +ve
Will you accept this DBD donor?
Yes, I will accept this patient kidneys, because of low risk of acquiring hepatitis C virus infection in the recipient from anti HCV+/PCR- donors.
But the if the recipient is anti HCV –ve, then I will highlight the relative risk of graft loss more when having anti HCV-ve donors, but however, being transplanted is better than being long time on waiting list, and on dialysis.
The recipient should be screened as follow: do HCV PCR at 3-7 days post Tx, repeated by day 10-14, then by 6 weeks post-transplant, if negative reassurance and no need for DAA therapy, if positive at any stage of screening then start DAA within 3-10 days of positive test for 12 weeks, and confirm sustained viral response.
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Yes, I will accept this donor as a live donor to an HCV positive recipient.
Will send the recipient and donor for a hepatologist, for evaluation of portal hypertension, and assessment of hepatic fibrosis, as in a potential recipient with advanced liver fibrosis can go for simultaneous liver kidney transplantation.
I would start DAA for both donor and recipient before transplantation, if time allowed before transplant, and achieving HCV cure, before kidney harvesting.
Or, I will consider early start of DAA therapy, in order to prevent the deleterious consequence (fibrosing cholestatic hepatitis) that could occur in 10% of such cases, and other extrahepatic manifestations such as cryoglobinemia, vasculitis and PTLD.
This would be explained to the patient as the decrease wait time to transplant, reduce mortality.
Assuming HCV PCR is not available, how would you manage the case?
I would go ahead for transplantation, with frequent monitoring as mentioned above, and when become positive I will start treatment with DAA.
References:
(1) Seeff LB. Natural history of chronic hepatitis C. Hepatology. 2002 Nov;36(5 Suppl 1):S35-46. doi: 10.1053/jhep.2002.36806. PMID: 12407575.
(2) Daloul R, Pesavento TE, Goldberg DS, Reese PP. A review of kidney transplantation from HCV-viremic donors into HCV-negative recipients. Kidney Int. 2021 Dec;100(6):1190-1198. doi: 10.1016/j.kint.2021.06.034. Epub 2021 Jul 6. PMID: 34237327.
(3) Czarnecka P, Czarnecka K, Tronina O, Baczkowska T, Durlik M. Utilization of HCV viremic donors in kidney transplantation: a chance or a threat? Ren Fail. 2022 Dec;44(1):434-449. doi: 10.1080/0886022X.2022.2047069. PMID: 35260039; PMCID: PMC8920354.
(4) Kucirka LM, Singer AL, Ros RL, Montgomery RA, Dagher NN, Segev DL. Underutilization of hepatitis C-positive kidneys for hepatitis C-positive recipients. Am J Transplant. 2010 May;10(5):1238-46. doi: 10.1111/j.1600-6143.2010.03091.x. Epub 2010 Mar 26. PMID: 20353475.
(5) Chascsa DM, Mousa OY, Pungpapong S, Zhang N, Chervenak A, Nidamanuri S, Rodriguez E, Franco D, Ryland K, Keaveny AP, Huskey JL, Smith M, Reddy KS, Taner CB, Vargas HE, Aqel BA. Clinical outcomes of hepatitis C treatment before and after kidney transplantation and its impact on time to transplant: A multicenter study. Am J Transplant. 2018 Oct;18(10):2559-2565. doi: 10.1111/ajt.14931. Epub 2018 Jun 8. PMID: 29758123.
Thank you for your reply. This is a picture of a patient who was treated or cleared the HCV. The HCV antibodies indicated past infection. We need to make sure that there is no HCV-associated nephritis.
Yes, for a living donor, I will exclude liver disease also. Well done. This is a model answer.
Thank you Prof.
Our deceased donor is HCV antibody is positive, but HCV PCR is negative.
Which carries three possibilities .
A-No active HCV infection.
B-Cleared or treated HCV infection.
C-False positive antibody.
Will you accept this DBD donor?
Yes, I will .
As our donor is HCV positive by serologic testing but NAT negative (nonviremic) and these donors have not been documented to transmit HCV infection(1).
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Yes, I will.
As studies shown that long-term outcome of HCVR+ transplanted with kidneys from HCVD+ seems good in terms of patient survival, graft survival and liver disease and HCVD+ was not a significant risk factor for mortality, graft failure and liver disease among HCVR+.(2)
Hepatic conditions to be met for the recipient might be compensated cirrhosis, or early fibrosis with absence of portal hypertension, will go ahead to transplant and then treat with DAA after the surgery for 12 weeks according to the genotype with strict follow up.
However, if there is decompensated cirrhosis and portal HTN > 10mmHg with hepatologist assessment, will look for simultaneous liver and kidney transplantation and then treat the recipient with DAA after the surgery.
Close follow-up of patients with careful monitoring for early detection of post-transplant liver complications might have been decisive.
Assuming HCV PCR is not available, how would you manage the case?
I will go with transplantation considering our donor as HCV PCR positive, then follow up recipient HCV PCR as per BTS guidelines if came positive I will treat with DAAs.
References:
1- (KDIGO guideline) TREATMENT OF HCV IN KIDNEY TRANSPLANTRECIPIENTS
2- Position Statement on the use of Organs from Hepatitis C Viraemic Donors and Increased Infectious Risk Donors in Hepatitis C Negative Recipients(BTS)
3-Morales JM, Campistol JM, Domínguez-Gil B, et al. Long-term experience with kidney transplantation from hepatitis C-positive donors into hepatitis C-positive recipients. Am J Transplant. 2010;10(11):2453-2462. doi:10.1111/j.1600-6143.2010.03280.x.
In the second question R PCR is a must,
1-You were offered kidneys from a 56 -year-old male DBD (donor after brain stem death) donor who suffered from SAH (grade 5) complicating cerebral aneurysm. His retrieval S Cr was 78 µmol/L. Virology was reported as follows: HBsAg negative, HBsAb negative, HBcAb negative, and both HBeAg and HBeAb are negative. HCV antibody is positive, but HCV PCR is negative. HIV is negative.
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Will you accept this DBD donor?
History
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Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
HCV+ to HCV+ Kidney Transplantation
HCV+ to HCV− Kidney Transplantation
what are the conditions that should be met?
In the absence of a living donor, these patients have two options:-
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Assuming HCV PCR is not available, how would you manage the case?
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Reference
Exellent, very clear.but what is your decision in the last question?
What if both PCR,and NAT are not available.!
Many thanks Prof.Dawlat
what is your decision in the last question? What if both PCR,and NAT are not available.!
My decision go to transplant
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yes I will accept the donor
as per the recent recommendations organs from hepatitis C infected donors may be transplanted into uninfected recipients
with the following precautions
· consent to receive a HCV D+ organ
· should be avoided in recipients with advanced fibrosis or cirrhosis.
· To be seen by a liver specialist
· longitudinal testing for hepatitis C RNA of the recipient post transplant to ensure appropriate and early intervention if HCV transmitted AS FOLLOW
HCV PCR day 3-7——-If negative repeat day 10-14 ——– negative repeat 6 week post transplant ——- negative then manage as standard recipient
At any time positive PCR Start DAA within 3-10 working days of frist positive PCR
if PCR for recipient is not available The approach will be the same I will accept and then frequent monitor(same previous approach
UK Position Statement on the use of Organs from Hepatitis C Viraemic Donors and Increased Infectious Risk Donors in Hepatitis C Negative Recipients
1.the first scenario the donor is not viremic so not infective.!
I will accept the donor as he is PCR negative. Being positive for HCV antibodies is not a contraindication for kidney donation as there is no clear history of risky behavior such as IV drug abuse which might predispose to reinfection. Similarly, there is no history of failed therapy or SVR.
Transplanting HCV positive donor kidney to HCV positive recipient was proved to be effective approach in shortening the waiting time on transplant list, as DAA is effectively treating the donor post transplantation. Tha landmark studies Thinker and Expander advocated the utilization of HCV infected donors with either vigilant approach with low threshold to treat, once HCV infection diagnosed. Prophylactic treatment started prior to transplantation as majority of recipients would be converted to HCV positive infection.
No consensus is known about best method to approach those patients with potential HCV positive donors.
I would suggest close observation and follow up of the patients with positive donors and to implement treatment once diagnosed with HCV infection as success rate with DAA therapy exceed 95%.
Reference:
1]Pagan et al.Should my patient accept a kidney from a hepatitis C virus-infected Donor?.Kidney 3601[2]:p127-129,Feb.2020
Thankyou please refer to BTS guidelines.
Will you accept this DBD donor?
Yes, I would accept this DBD donor, as the donor is HCV PCR negative, but antibody positive, which means there is no active HCV infection or replication.
The recipient just needs to be counselled regarding the past HCV infection in the donor.
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Assuming HCV PCR is not available, how would you manage the case?
We would still accept the donor with antibody postive and would consider him as HCV positive.
We would like to start peri operative DAA and would monitor him closely with PCR in the follow-up.
UK Position Statement on the use of Organs from Hepatitis C Viraemic Donors and Increased Infectious Risk Donors in Hepatitis C Negative Recipients
Also is the in HCV positive donor, if the time to transplant is >24 weeks, I would like to treat the liver donor with DAA and document SVR before transplant.
Thankyou for a comprehensive answer with clear decisions.
Will you accept this DBD donor?
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Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
===============================
Assuming HCV PCR is not available, how would you manage the case?
References
Well done.
1- yes , will accept the donor , the donor is HCV Ab positive with negative PCR means non viremic HCV.
2- yes will accept , provided that DAA will be given to the patient perioperative or post operative or within 90 days of transplantation, also liver biopsy of the recipient should be done to detect cirrhotic or not
3- if PCR is not available, will accept if there is no other option for any other donor and will start DAA perioperative for 3 months with close follow up by PCR
references:
1- lecture of prof May Hassaballah
2- Ronit Patnaik, MD, Eugenia Tsai. Hepatitis C Virus Treatment and Solid Organ Transplantation. Gastroenterology & Hepatology Volume 18, Issue 2 February 2022
Too SHORT !!
Perioperative!
How close is close followup.
Will you accept this DBD donor?
Yes, provide the recipient accepts the offer and gets consented to go with the transplantation from HCV +ve donor but negative PCR which indicates previous infection with SVR either following treatment with DAA or spontaneous clearance.
Will you accept this donor as a live donor if the recipient is also HCV-positive? If yes, what are the conditions that should be met?
KDIGO guidelines recommended that all kidney transplant candidates with HCV be considered for DAA therapy, either before or after transplantation (1A).
Factors that affect the timing of the treatment included the type of donor living vs DD (anticipate waiting time)The severity of liver fibrosis, and portal hypertension
the willingness of the patient and program to accept an organ from an HCV-infected donor.
Yes, provided that the recipient with HCV positive needs to do HCV RNA- PCR or NAT assay to confirm he is viremic or not and assess for any evidence of liver cirrhosis or portal hypertension
If F0 to compensated cirrhosis without portal hypertension still can go for isolated kidney transplantation and if the short term for transplantation is less than24 weeks preferred to be treated with DAA after transplantation while if the expected time for transplantation > 24 weeks then treatment can be done before or after transplantation, the patient should consent and risk stratification and benefit addressed and explained to him, also drug-drug interaction should be addressed especially with CNI and DAA
If the recipient with decompensated liver cirrhosis and moderate to severe portal hypertension hepatic venous pressure gradient > 10
mm Hg or evidence of portal hypertension on imaging he should go for dual liver and kidney transplantation before treatment
Mild to moderate portal hypertension should be considered case by case
the recipient has no evidence of HCV-related kidney disease like MGN, MPGN, proteinuria and
And after checking HCV PCR for both donor and recipient if positive should offer the DAA therapy for 12 weeks and assuring SVR before or after transplantation based on waiting time.
Assuming HCV PCR is not available, how would you manage the case?
All living kidney donors should be screened for HCV infection with immunoassay and NAT if seropositive (1). HCV NAT has a sensitivity of 85% to 100% and a specificity of 99% to 100% (2).
It is significant to differentiate between a seropositive and viremic donor when debating organ transplant from an HCV-positive donor.
An HCV-seropositive donor that is NAT positive (viremic) is considered to have an active infection and carriages a high risk for disease transmission while HCV positive but NAT negative (nonviremic) is considered to have either spontaneous clearance or effective treatment of infection or have a false-positive antibody result, with low risk for transmitting HCV infection.
However, Kidneys from HCV-infected donors can be offered to potential recipients regardless of HCV status, provided that national or regional laws and
regulations allow this practice and assuring the availability of the DAA therapy once indicated after transplantation with a high cure rate of> 95%
so still can go ahead with accepting this donor and provide a full explanation to the recipient. With possible HCV infection early after transplantation which mandates close and frequent HCV PCR monitoring with DAA availability once indicated
References
1. Martin P, Awan AA, Berenguer MC, Bruchfeld A, Fabrizi F, Goldberg DS, Jia J, Kamar N, Mohamed R, Pessôa MG, Pol S, Sise ME, Balk EM, Gordon CE, Adam G, Cheung M, Earley A, Jadoul M. Executive Summary of the KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease. Kidney Int. 2022 Dec;102(6):1228-1237.
2. Patnaik R, Tsai E. Hepatitis C Virus Treatment and Solid Organ Transplantation. Gastroenterol Hepatol (N Y). 2022 Feb;18(2):85-94. PMID: 35505819; PMCID: PMC9053510.
Well done as usual.
Interpretation of this donor according his virology:
HBsAg / HBsAb / HBcAb / HBeAg / HBeAb——- (negative)
HCVAb (positive) / HCV PCR (negative)
HIV (negative)
This patient is negative to (HBV& HIV) but this patient has (HCV Ab positive)
My impression;
(No active HCV infection , or cleared or treated HCV infection, or false-positive antibody)
1-Will you accept this DBD donor?
Yes; I will accept this DBD donor
According KDIGO-2022 guidelines;
-Kidney transplantation is the best therapeutic option for patients with CKD G5 irrespective of presence of HCV infection. (1A)
-After assessment of liver fibrosis, HCV-infected potential living kidney donors who do not have cirrhosis should undergo HCV treatment before donation if the recipient is HCV-uninfected; they can be accepted for donation if they achieve sustained virologic response (SVR) and remain otherwise eligible to be a donor. (Not Graded)
2-Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Yes; I will accept this alive donoe (D+HCV/R+HCV)
-Considering Consultation with a hepatologist to ensure the patient is not at increased risk of progressive liver disease with deferred treatment.
-However, the patient needs to provide written informed consent to receive a kidney from an HCV-infected donor (even though the patient already is infected).
-When the expected waiting time for a kidney allograft from an HCV-infected donor is long, the patient should be offered HCV therapy before transplantation.
-Potential living donors with HCV infection should be treated for HCV as in the general population and liver fibrosis should be assessed.
-Kidney function and proteinuria should be monitored during and after DAA therapy.
According KDIGO-2022 guidelines;
-All kidney transplant candidates with HCV be evaluated for severity of liver disease and presence of portal hypertension prior to acceptance for kidney transplantation. (2D)
-Patients with HCV, compensated cirrhosis and no portal hypertension undergo isolated kidney transplantation while patients with decompensated cirrhosis or clinically significant portal hypertension (i.e., hepatic venous pressure gradient ≥10 mm Hg or evidence of portal hypertension on imaging or exam) undergo a simultaneous liver-kidney transplantation. (1B) ,Those with mild-to-moderate portal hypertension should be determined on a case-by-case basis.
-Referring patients with HCV and decompensated cirrhosis for combined liver-kidney transplantation. (1B)
-Timing of HCV treatment in relation to kidney transplantation (before vs. after) should be based on donor type (living vs. deceased donor), waitlist times by donor type, center-specific policies governing the use of kidneys from HCV-infected deceased donors, and severity of liver fibrosis. (Not Graded)
-All kidney transplant candidates with HCV be considered for DAA therapy, either before or after transplantation. (1A)
-HCV-infected kidney transplant candidates with a living kidney donor be considered for treatment before or shortly after transplantation depending on the anticipated timing of transplantation. (2B)
-Kidney transplant recipients being treated with DAAs be evaluated for the need for dose adjustments of concomitant immunosuppressants. (1C)
-HCV-infected kidney transplant recipients should be tested at least every 6 months for proteinuria. (Not Graded)
3-Assuming HCV PCR is not available, how would you manage the case?
-All deceased donors should be tested for HCV NAT prior to organ procurement, and ideally before the organ is offered to potential recipients.
-HCV-NAT positive patients who are candidates for kidney transplantation should be evaluated for the presence of cirrhosis using either a noninvasive fibrosis-staging method or, on occasion, a liver biopsy.
According KDIGO-2022 guidelines;
-All kidney donors be screened for HCV infection with both immunoassay and NAT (if NAT is available). (1A)
-Patients previously infected with HCV who achieved SVR before transplantation undergo testing by NAT 3 months after transplantation or if liver dysfunction occurs. (2D)
References;
-Chascsa DM, Mousa OY, Pungpapong S, et al. Clinical Outcomes of Hepatitis C Treatment Before and After Kidney Transplantation and Its Impact on Time to Transplant: A Multi-Center Study. Am J Transplant 2018; 18: 2559-2565.
-Potluri VS, Goldberg DS, Mohan S, et al. National Trends in Utilization and 1-Year Outcomes with Transplantation of HCV-Viremic Kidneys. J Am Soc Nephrol 2019; 30: 1939-1951.
-Diethelm AG, Roth D, Ferguson RM, et al. Transmission of HCV by organ transplantation. N Engl J Med 1992; 326: 410-411.
-European Best Practice Guidelines for Renal Transplantation. Section I: Evaluation, selection and preparation of the potential recipient. Nephrol Dial Transplant 2000, 15 (suppl 7): 3-38.
Thankyou well done.
Will you accept this DBD donor?
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Yes, will accept him, criteria for HCV +ve donor to HCV +ve recipient are:
Assuming HCV PCR is not available, how would you manage the case?
Source:
-Hepatitis C virus treatment and solid organ transplantation by Ronit patnaik et al.
-UK position on the use of organ from HCV donors and increased infectious risk donors in Hepatitis negative recipients
The 8th condition will be a PCR for the R!!! why did you presume he is the same as the donor.
Well done.
Thanks prof, yes
Will you accept this DBD donor?
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Assuming HCV PCR is not available, how would you manage the case?
Please reconsider your last answer!
what can we do if PCR test is not available?
NAT test is the same as PCR with the same technology. it is not different.
Will you accept this DBD donor?
Yes, I will accept.
The recipient and the team must be aware of the positivity of the serological status and follow-up in the post-transplant outpatient clinic with programmed dosages of RT PCR HCV.
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Yes, it is possible.
However, extensive investigation of liver function and structure is necessary to avoid unnecessary transplantation and immunosuppression.
Impaired liver function (widened INR, low platelets, high bilirubin values), clinical conditions resulting from structural liver disease (ascites, collateral circulation, disorientation), and active neoplasms (hepatocarcinoma) are situations that would suspend transplantation immediately.
A positive viral load in a patient waiting for a deceased donor would not prevent the immediate initiation of medication. If there is a schedule for a living donor, the ideal is to proceed with the treatment and wait for its completion in twelve weeks with a sustained viral response.
Depending on renal function, ribavirin may be excluded if CrCl < 30 (which would occur in those awaiting transplantation).
Avoid induction with rATG and rituximab, prioritizing IL2R blockage.
Assuming HCV PCR is not available, how would you manage the case?
Monitor the recipient’s viral load frequently over the next two years and start a hepatitis C regimen if the viral load is positive.
Interferon-free schemes are preferable, in Brazil the most used scheme is Sofosbuvir with Ledispavir. Although the first has little interaction with immunosuppressants, the second can interact with everolimus and calcineurin inhibitors.
Thankyou for mentioning the treatment of R on the waiting list .!
You can follow the BTS guidelines if the PCR is not available and consider him +ve.
Will you accept this DBD donor?
Yes i will accept
Transplant facilities must make sure that patients receive education.
Discussions with team to give informed consent before performing kidney transplants.
Patients should be advised about the advantages and hazards of receiving an HCV-infected kidney transplant,
Also regarding the requirement for DAA therapy.
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
Yes Transplantation is possible;
Living donation is possible if there isn’t extensive hepatic fibrosis or indications of kidney dysfunction.
If both the donor and recipient have HCV, treatment of the donor may be postponed if the transplant is timely and helps the recipient (e.g., avoids dialysis for a recipient with poor vascular access), with few risks anticipated for the donor.
Regarding patient survival, graft survival, and liver disease, the long-term results of HCVR+ kidney transplantation with kidneys from HCVD+ patients appear promising.
Among HCVR+, HCVD+ did not significantly increase the risk of death, graft failure, or liver disease.
These results strongly imply that kidney transplantation from HCVD+ patients into HCVR+ patients is a secure long-term technique that aids in kidney preservation.
Assuming HCV PCR is not available, how would you manage the case?
I will treat the recipient with DAAs if the HCV PCR results are positive and I will manage the recipient with close follow-up as per BTS guidelines. I will consider the potential donor as HCV positive.
References
The impact of transplantation with deceased donor hepatitis c-positive kidneys on survival in wait-listed long-term dialysis patients
Kevin C Abbott 1 , Krista L Lentine, Jay R Bucci, Lawrence Y Agodoa, Thomas G Peters, Mark A Schnitzler
Long-Term Experience With Kidney Transplantation From Hepatitis C-Positive Donors Into Hepatitis C-Positive Recipients
J. M. Morales, J. M. Campistol, B. Domínguez-Gil, A. Andrés, N. Esforzado, F. Oppenheimer, G. Castellano, A. Fuertes, M. Bruguera, M. Praga
KDIGO 2022 CLINICAL PRACTICE GUIDELINE FOR THE PREVENTION, DIAGNOSIS, EVALUATION, AND TREATMENT OF HEPATITIS C IN CHRONIC KIDNEY DISEASE
Well done
In the first scenario with only HCV Ab + could be due to past infection and immunity ,if PCR is – so he is not viremic or infective.
ok prof
Yes, with the following precautions:
We recommend that kidneys from HCV-infected donors be considered regardless of the HCV status of potential kidney transplant recipients (1C).
: When transplanting kidneys from HCV-infected donors into HCV-uninfected recipients, transplant centers must ensure that patients receive education and are engaged in discussion with sufficient information to provide informed consent. Patients should be informed of the risks and benefits of kidney transplantation with an HCV-infected kidney, including the need for DAA treatment.
: When transplanting kidneys from HCV- infected donors into HCV-uninfected recipients, transplant centers should confirm the availability of DAAs for initiation in the early post-transplant period
After assessment of liver fibrosis, HCV-infected potential living kidney donors who do not have cirrhosis should undergo HCV treatment before donation if the recipient is HCV-uninfected; they can be accepted for donation if they achieve sustained virologic response (SVR), no hepatic or extrahepatic manifestations, and remain otherwise eligible to be a donor.
Living donors with HCV infection: We recommend antiviral therapy before kidney donation for chronic HCV carriers. Short (8–12 week) DAA regimens treat most HCV infections. After 12 weeks, sustained virologic response (SVR) indicates an HCV cure. Hence, this strategy reduces the possibility of HCV transmission to HCV RNA-negative recipients or superinfection with another genotype among HCV RNA-positive recipients.
Data are lacking on the safety of transplanting a kidney from an HCV-seropositive live donor who has had effective antiviral therapy into an HCV-negative recipient or an HCV RNA-positive recipient with a different genotype.
Transplant facilities must educate and notify patients before transplanting HCV-infected kidneys into HCV-uninfected recipients.
Patients should be advised of the risks and advantages of HCV-infected kidney transplantation, including DAA therapy.
Start pan-genotypic DAA directly, until the genotype analysis appears.
Close monitoring of PCR(HCV) RNA and LFTs post-transplant
References:
KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease.
Cruzado JM, Gil-Vernet S, Castellote J, et al. Successful treatment of chronic HCV infection should not preclude kidney donation to an HCV-negative recipient. Am J Transplant 2013; 13:2773.
Sarrazin C, Isakov V, Svarovskaia ES, et al. Late Relapse Versus Hepatitis C Virus Reinfection in Patients With Sustained Virologic Response After Sofosbuvir-Based Therapies. Clin Infect Dis 2017; 64:44.
Just consider the donor with unavailable PCR as +ve and proceed from there ( assuming he is a DD)
But if it is a LD ! with unavailable lab facility then make sure ADD are available and proceed from there.
Yes because;
Studies suggest that morbidity and mortality of HCV-seropositive recipients are not increased by the transplantation of kidneys from HCV-seropositive donors.[4] in order to differentiate between compensated vs decompensated liver disease with portal hypertension, the following tests should be done if not conclusive or high suspicion of cirrhosis than can do liver biopsy. it would help to differentiate whether to do kidney transplant or liver kidney combine transplantation.
HVC core antigen test should be performed in resource limited areas. Core antigen assay has sensitivity and specificity for detecting HCV viremia of approximately 93 and 99 percent.[5]
References
If PCR is not available ,it is fair to conider him as +ve and deal with according to BTS algorithm.
Will you accept this DBD donor?
Yes, I will accept this DBD because the interpretation of the result could be:
Will you accept this donor as a live donor if the recipient is also HCV-positive? If yes, what are the conditions that should be met?
-Conditions to be met for the recipient
IF the above “a” and “b” conditions are met, but the living kidney is only available within 24 hours, I will go ahead to transplant and then treat with DAA after the surgery for 12 weeks according to the genotype
IF the above “a” and “b” conditions are met, and the living kidney will be available for more than 24 hours, I will treat the recipient with DAA for 12 weeks before the surgery according to the genotype
However, if there is
I will evaluate for simultaneous liver and kidney transplantation and then treat the recipient with DAA after the surgery
Condition for the donor (not graded)
Following assessment for liver fibrosis and exclusion of cirrhosis, the donor is advised to receive treatment for HCV with SVR before proceeding to donate the kidney
Assuming HCV PCR is not available, how would you manage the case?
As it has been stated in the KDIGO guideline that the risk of transmitting HCV infection from HCV PCR recipient to recipient is minimal, then I will go ahead with the transplantation if the recipient is confirmed to be positive for HCV PCR and treat with DAA according to genotype post-surgery
In addition, tests like Fibroscan, and liver biopsy can be done for the donor to detect the presence of fibrosis or cirrhosis, and the stage will determine if DAA can be used for treatment before the surgery
References
Thankyou , a wise plan if a donor PCR is not available is to consider him positive!
A practical algorithm is offered by BTS for that situation,quoted by your collegue Mohamad Esmat.
Thank you, prof. Dawlat for your response.
Will you accept this DBD donor?
In general, Hepatitis C virus (HCV) infection causes varieties of kidney disease in native and transplanted kidneys. Kidney transplant recipients with HCV infection, if HCV is not treated after transplantation will have a worse patient and allograft survival after transplantation compared with kidney transplant recipients without infection.
The potential donor has HCV Ab positive and HCV PCR negative:
-Most likely represents prior infection that subsequently cleared spontaneously (or following successful therapy).
-A false-positive antibody tests due to technical reasons.
– passively acquired from blood transfusions. which unusually nowadays.
-The amount of HCV RNA may be below the limit of detection of the assay.
My answer it will be yes, I will accept the offer with close monitoring of recipient after transplantation initially with AB test and by PCR if Ab test came positive.
Will you accept this donor as a live donor if the recipient is also HCV positive? If yes, what are the conditions that should be met?
In this case we have a potential donor without prove of chronic HCV infection (Ab positive and PCR is negative).
In the other side we have a recipient with proved HCV infection, so the management will be as following:
Basically, HCV infection prior to transplantation, when not successfully treated, increases posttransplant morbidity and mortality,but patients with HCV infection have a lower mortality with transplantation compared with remaining on dialysis.
-Staging of liver disease (assessing extent of fibrosis) is a standard component of the evaluation of patients with HCV infection: Staging is initially performed with non-invasive testing, which include blood tests and imaging tests ; transient elastography (TE) or aspartate aminotransferase (AST)-to-platelet ratio index (APRI).
-A liver biopsy may be needed.
-Results of these staging tests can tell regarding liver-related prognosis, selection of HCV treatment regimen, and the decision on kidney versus combined kidney-liver transplantation.
-If there is proved cirrhosis, patient indicated for portal hypertension assessment. If there is decompensated cirrhosis or portal pressure more than 10 mmHg, he will be indicated for combined kidney-liver transplantation.
-Anti viral therapy (DAAs) either pre or post transplantation, case by case as per availability of the donor.
Assuming HCV PCR is not available, how would you manage the case?
I will consider the potential donor as HCV positive, and I will accept the offer
And manage recipient with close follow up with HCV PCR as per BTS guidelines if came positive I will treat with DAAs.
References
Awan AA, Jadoul M, Martin P. Hepatitis C in Chronic Kidney Disease: An Overview of the KDIGO Guideline. Clin Gastroenterol Hepatol 2020; 18:2158.
Liu CH, Liang CC, Huang KW, et al. Transient elastography to assess hepatic fibrosis in hemodialysis chronic hepatitis C patients. Clin J Am Soc Nephrol 2011; 6:1057.
Jadoul M, Horsmans Y. Impact of liver fibrosis staging in hepatitis C virus (HCV) patients with kidney failure. Nephrol Dial Transplant 2014; 29:1108.
Well done.
Transplantation of a kidney from an HCV RNA +ve kidney donors directly causes HCV infection in the recipient .HCV infection has been associated with increased morbidity and possibly mortality in kidney transplant recipients , but recipients of kidneys from HCV seropositive /RNA positive donors still have better outcomes compared with those who remain on dialysis.
First of all , i will accept this DBD donor with the -ve HCV PCR
If this donor was a live donor and the recipient was also HCV positive :
-Using kidneys from HCV-seropositive donors in HCV seropositive recipients may be a safe approach in the long term as the risk of increased mortality is overweighed by the survival benefits , as well as the effectivity of the DAA’s the may possibly cure HCV infection after the Tx.
–In 2018 the KDIGO guidelines recommended that kidneys from sero+ve donors should be given only to sero+ve recipients , however the use of HCV RNA -+ve kidneys in sero-ve recipients followed by early administration of DAA’s was describes in a variety of pilot trials with good results.
–In recipients with HCV liver staging should be done using non-invasive techniques after labs and chemistery , as elastography.Liver biopsy may be done occasionally .
–Candidates with decompensated cirrhosis , severe portal hypertension are listed for combined liver kidney Tx .
–DAA’s timing is selected accordingly either pre or post transplant along with monitoring and follow up.
–The British Viral Hepatitis Group has recently issued a position statement on the use of organs from hepatitis C viraemic donors in hepatitis C negative recipients- diagram attached .
References :
1-Hand book of Transplantation -6th edition
2-KIDIGO-2018
3-BTS position statement
4-UP to date – HCV and kidney transplantation
A one year outcome after kidney transplantation from HCV +ve donors to HCV-ve recipients
Well done ,obviously the BTS algorithm is more accommodating which is the general accepted trend after having DAA.
HCV antibody is positive, but HCV PCR is negative==> therefore I will accept this donor
HCV antibody is positive, but HCV PCR is negative==> therefore I will accept this donor even he is a living donor
However, if the recipient has PCR HCV positive,
==>
we should evaluate the liver fibrosis and the portal prussure in the recipient
If there is decompensated cirrhosis or portal pressure more than 10 ==> the recipient needs SLK transplant
If No ==>then , we should know if the living donor will remain available more than 24 weeks
If yes ==> recipient will be treated before renal transplantation
If no ==> recipient will be treated after RTX
In this case I will consider this deceased donor as HCV pos
Therefore if the recipient is also HCV pos ==> we will accept this donor and start post renal treatment DAA
If the recipient is HCV negative ==> we should evaluate the waiting list period and compare between comorbidities and mortalities staying on waiting list
We should inform the recipient about the risk of infection
Trial of Transplantation of HCV-Infected Kidneys into Uninfected Recipients
• Thinker trial:safety and efficacy of transplanting HCV genotype-1 viremic kidneys into HCV-negative recipients (10 pts)
• All recipients tested positive for HCV RNA on day 3 post-transplantation and were subsequently treated with elbasvir/grazoprevir (EBR/GZR)
• all patients achieved sustained virologic response 12 weeks after the end of treatment (SVR12) and showed good allograft function
The strategy of management of donor pos to recipient negative depending on BtS recommendations
1 recipient tested for PCR HCV in day 3- 7
If negative
2- The test is repeated in day 10-14 post transplantation
If negative
3- The test is repeated in 6 weeks post-transplant
DAA started 3 to 10 days after any positivity of PCR HCV
Prophylactic initiation
given right before transplantation and for 7 days
REFERENCES
1- Kidney Txin patients with HCV professor May A. Hassaballa lecture
2- (KDIGO guideline) TREATMENT OF HCV IN KIDNEY TRANSPLANTRECIPIENTS
3- Position Statement on the use of Organs from Hepatitis C Viraemic Donors and Increased Infectious Risk Donors in Hepatitis C Negative Recipients(BTS)
Well done but in the first scenario the R is HCV Ab +ve did you assume he is NAT -ve!
This point has to be evaluated.