2. 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 65 µmol/L. Virology was reported as follows: HBsAg negative, HBsAb negative, HBcAb negative, and both HBeAg and HBeAb are negative. HCV antibody and HCV PCR are positive. HIV is negative
· 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.
.. Will you accept this allograft?
Yes.
.. If yes how you will proceed?
Yes, I will council the family,
will start DAA as soon as possible,
Will prefer induction with basiliximab,
Maintenance immunosuppression with as usual with triple regime.
Will follow the LFTs, HCV PCR surveillance at 3, 7, 10, 14 days and after 6 weeks.
Reference;
.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9053510/.
. Will you accept this DBD donor? this donor is deceased donor with positive HCV Ab and HVC RNA which indicate active viral infection. In case of organ donation, the risk of transmission is high but still it is not contraindicated due to the advent of DAAS leading to >95% cure rates and the ease of treating HCV posttransplant but still we have to counsel the patient about the risk of infection. A recent report demonstrated high cure rates even in the liver transplant setting, suggesting that immunosuppression does not impede eradication and that the interactions between HCV and transplant drugs can be successfully managed 2. If yes, how would you proceed?
-Testing recipient for HCV AB and RNA, ALT , AST, AFP.
-If HCV-negative: he should receive DAA (SOF-based) therapy for 12 weeks separate open-label trial demonstrated 100% SVR12 with 12 weeks of elbasvir/grazoprevir (± sofosbuvir) therapy initiated immediately prior to transplantation in 10 HCV-uninfected kidney transplant recipients of allografts from HCV-viremic donors
-If the Recipient is HCV-RNA positive : this condition is associated with higher risk of viral replication, acute hepatitis, chronic hepatitis and cirrhosis, also extrahepatic manifestations of HCV as GN is an important risk. -Liver function , AFP , fibroscan , liver biopsy should be done If Compensated liver so,kidney transplant can be done with initiation of DAA treatment immediately before transplant.
-According to KIDIGO guidelines: – viral RNA every 3-6months, AFP and liver USG every 6months for life -If decompensated liver disease– combined liver + kidney transplantation. With follow up for life also . – it is important to investigate foe presence of HCC before TX or de novo post TX -it is recommended that the candidates is considered for DAA therapy, either before or after transplantation. -kidney transplant recipients being treated with DAAs be evaluated for the need for dose adjustments of concomitant immunosuppressants . -patients previously infected with HCV who achieved SVR before transplantation undergo testing by NAT 3 months after transplantation or if liver dysfunction occurs . -HCV-infected kidney transplant recipients should be tested at least every 6 months for proteinuria (Not Graded).
Perform HCV PCR on post transplant 3-7day, 10-14day and 6 week, if negative then no transmission of HCV and reassure the patient. If positive then start DAA within 3-10working day for 3 month. Then SVR tested after 3 month of completion of DAA. if futher positive then another 3 month of DAA of other combination.
Q1: Yes, the donor has an active HCV infection, but according to the KDIGO guideline, if the donor has no HCV-associated nephritis (HCVAN), this kidney is considered for transplantation without considering HCV status, but DAA therapy should be considered.
Q2: DAA treatment should be initiated very soon if HCV PCR of the patient become positive and patient should be informed about the importance of situation and DAA treatment and follow-up.
Induction therapy with basiliximab is preferred. Maintenance immunosuppressive therapy with triple- therapy and HCV PCR monitoring at 3, 7, 10, 14 days and six-weeks later is recommended.
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 given recipient is offered a kidney from a 56 year old DBD…There is normal renal function…Cause of Brain stem death is subarachnoid hemorrhage….There is no evidence of Hep B or HIV…..There is evidence of Anti HCV and HCV RNA is also detected in the donor….There is underlying active HCV infection in the donor
HCV status of the recipient has not been provided…..As per the KDIGO guidelines, I will accept the donor irrespective of the recipient HCV RNA status…The donor has active HCV Infection with viremia…There is a high chance of transmission to the recipient as per the available literature….
The recipient has to be counselled about the above scenario and the need to start DAA immediately post transplant and monitor the HCV viral load….I would emphasize the monitoring of the HCV Viral load regularly….We should test HCV RNA quantitative on Day 3, day 7, day 14 and 6 weeks later…
As the recipient would be waiting on the deceased donor list, it is always better to have a renal transplant earlier rather than waiting for a HCV negative donor…With the advent of DAA, there is very less chance of progression of HCV in the recipient into chronic infection and cirrhosis….
If the scenario is a live donor with HCV positive:
In this case the donor health becomes a prority…The donor should be evaluated for features of LFT, RFT, urine routine, CBC, PT INR, USG whole abdomen, Fibroscan to rule of CLD..The donor should get done HCV RNA qauntitative done and treated before Transplant…It is best to treat HCV in the donor and then plan for elective surgery as surgery with High HCV has chances of activation of HCV into fulminant hepatitis….
Yes, today direct-acting antiviral (DAA) therapy also shows excellent results as a preventive therapy for the development of HCV infection.
– 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
– Treatment for a period of 12 weeks with antiviral therapy
1. Will you accept this DBD donor? HCV Ab + and HVC RNA + indicates active viral infection (hepatitis) with high risk of transmission. but with the availability DAA, which is effective both pre- and post- transplant, this donor can be accepted, if the recipient accepts after understanding the risks. 2. If yes, how would you proceed? A. If Recipient HCV-negative: We can accept the donor, with DAA (SOF-based) therapy for 12 weeks, starting -12hr /0-hr of transplant. Recipient has to accept the risk of viral replication, hepatitis, associated complications; need for antivirals and side effects and life-long surveillance; including graft rejection and higher mortality. B. Recipient is HCV+: Donor HCV+ and Recipient HCV+ is associated with highest risk of viral replication, chronic hepatitis, cirrhosis and HCC; with Higher rate of all complications, graft-loss and mortality. Recipient liver disease and condition should be thoroughly evaluated. If Compensated liver disease à can proceed with kidney transplant, with DAA started peri-transplant; close monitoring of viral load, LFT, RFT, Tac C0 level and proteinuria. – Needs life-long follow-up: viral RNA every 3-6months, AFP and liver USG every 6months If decompensated cirrhosis – combined liver + kidney transplantation advised. Peri-op care, antivirals and follow up remain more stringent. KDIGO 2022 CLINICAL PRACTICE GUIDELINE For the Prevention, Diagnosis, Evaluation and Treatment of Hepatitis C in CKD recommends – · Kidney transplantation is the best therapeutic option for patients with CKD G5 irrespective of presence of HCV infection. · It is recommended that kidneys from HCV-infected donors be considered regardless of HCV status of potential kidney transplant recipients · The candidate with HCV should be evaluated for severity of liver disease and presence of portal hypertension prior to acceptance for kidney transplantation · HCV patient with compensated cirrhosis, and no portal hypertension can go for isolated kidney transplantation. · Patients with decompensated cirrhosis or clinically significant portal hypertension need a simultaneous liver–kidney transplantation. · It is recommended that the candidates is considered for DAA therapy, either before or after transplantation. · Post kidney transplant, recipients on DAAs needs evaluation for the need for dose adjustments of concomitant immunosuppressants.
1- This is an active viral hepatitis with high risk of transmission
but with the introduction of the DAA, this donor can be accepted
after explanation of the risks to the donor.
2- If the recipient is seropositive:
It is associated with higher all-cause mortality and higher all-cause graft loss.
and the recipient should be evaluated carefully regarding the liver function and
condition:
– If compensated, proceed and peri-transplant DAA should be started with close
follow-up
– If decompensated: combined liver and renal transplantatation
If the recipient is negative:
and accept the risk
we can accept with peri-transplantation SOF-based therapy for 12 weeks
· kidney transplantation is the best therapeutic option for patients with CKD G5 irrespective of presence of HCV infection.
· It is recommended that kidneys from HCV-infected donors be considered regardless of HCV status of potential kidney transplant recipients
· The candidate with HCV should be evaluated for severity of liver disease and presence of portal hypertension prior to acceptance for kidney transplantation
· HCV patient with compensated cirrhosis, and no portal hypertension can go for isolated kidney transplantation.
· patients with decompensated cirrhosis or clinically significant portal hypertension need a simultaneous liver–kidney transplantation.
· It is recommended that the candidates is considered for DAA therapy, either before or after transplantation.
· Post kidney transplant, recipients on DAAs needs evaluation for the need for dose adjustments of concomitant immunosuppressants.
KDIGO 2022 CLINICAL PRACTICE GUIDELINE FOR THE PREVENTION, DIAGNOSIS, EVALUATION, AND TREATMENT OF HEPATITIS C IN CHRONIC KIDNEY DISEASE
Yes I would accept this donor even though the risk of HCV transmission is high, but the donor can be started on DAA post-transplant, and it will reduce waiting time on HD. Prior to transplantation the recipient must be counselled regarding the risk of HCV transmission, complication of HCV infection, duration of DAA and side effects of DAA. DAA can be started before, or after transplantation depending on transplant center protocols. Start DAA (Glecaprevir/Pibrentasvir) pre-operatively then daily for 7 days. Follow up PCR of recipient should be done at 3-7 days, then day 14 and then at 6 weeks. If HCV PCR is negative then no need for DAA, If PCR positive then DAA should be started within 10 days of positive PCR, and continued for at least 12 weeks, then PCR should be repeated to confirm SVR. As far as induction immunosuppression is concerned, ATG and Almetuzumab should be avoided. Induction with Basiliximab is preferred.
DONOR WITH HCV positive for ANTIBODY AND PCR cab be accepted for HCV PCR positive recipient with more all cause mortality
for HCV PCR negative recipient
this is HISH RISK transplant
can be accepted after counselling and weighted benefit of transplant and risk of nor getting organ
Post op HCV PCR to be done at 2 week , 1 month and 3 month
SOF based DAA should be started immediately
Will you accept this DBD donor?
Yes I will accept this DBD donor
HCV infection in the donor does not amount to an absolute contraindication to donation of material for life-preserving transplantation, however the net benefit of transplantation must be considered against the risk of not receiving that specific transplant. This risk/benefit analysis allows for the potential use of a transplant from a HCV infected donor to a non-infected recipient.
If yes, how would you proceed?
Patient Consent
If the recipient is HCV PCR -ve >>> should be tested for HCV PCR day 3-7 post transplant if the result was negative so the test should be repeated on 10 – 14 days post transplant if also negative repeat the test after 6 weeks after that if negative reassurance of the recipient about low risk of HCV transmission.
If positive result at any time of previous testing time >>> confirmatory test should be done and to starting DAA at 3 to 10 working days of the first positive result .
Yes, donor can be accepted. HCV Ab positive denotes previous infection& PCR is negative.
How to process:
-Recipient counselling regarding the risk of HCV infection.
-Commencement of DAA peri-operatively.
-Monitoring of viral load following transplantation.
According to the KIDIGO guied line will accept this donor to the HCV positive recepient other wise recently emerge data stat that we can proceed with this RTX from HCV + donor to recepient – along with full councelling to the reciepeint and start him on DAA immediately post RTX .
use of HCV RNA-positive donors is no longer a major concern with the advent of DAA therapy
– an HCV RNA-positive donor can donate to an HCV RNA-positive recipient as well as to an HCV RNA-negative recipient as long as this is followed by antiviral treatment
– excellent HCV cure rates and excellent short-term graft function and safety profile have been reported
– DAA therapy should be offered in the peri-transplant period to reduce the risk of chronic HCV infection in the transplant recipient
1- This is an active viral hepatitis with high risk of transmission
but with the introduction of the DAA, this donor can be accepted
after explanation of the risks to the donor.
2- If the recipient is seropositive:
It is associated with higher all-cause mortality and higher all-cause graft loss. and the recipient should be evaluated carefully regarding the liver function and condition: – If compensated, proceed and peri-transplant DAA should be started with close follow-up – If decompensated: combined liver and renal transplantatation
If the recipient is negative:
and accept the risk
we can accept with peri-transplantation SOF-based therapy for 12 weeks
The 2018 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend that kidneys from HCV-seropositive and RNA-positive donors should only be given to HCV RNA-positive recipients. However, emerging data demonstrating the safety of transplanting kidneys from HCV RNA-positive donors into HCV RNA-negative recipients with early or pre-emptive DAA therapy support the use of kidneys from high-risk deceased donors in uninfected patients when medical need is urgent and the benefits appear to outweigh the risks. In all such cases, the recipient should receive specific counseling, be well informed, and participate in decision making.up to date
Now HC+R used for HB_R AND HC +R routine clinical practice.1
If yes, how would you proceed?
DAA therapy (Panp-genotypic DAA) in the post-transplantation 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.
Follow up post-transplant ,monthly and genotype and presence of resistance-associated
substitutions (RAS).
References:
1-Terrault, Norah et al .International Liver Transplantation Society Consensus Statement on Hepatitis C Management in Liver Transplant Recipients. Transplantation 101(5):p 956- 967, May 2017.
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 65 µmol/L. Virology was reported as follows: HBsAg negative, HBsAb negative, HBcAb negative, and both HBeAg and HBeAb are negative. HCV antibody and HCV PCR are positive. HIV is negative
Will you accept this DBD donor?
Yes, this will decrease wait time for recipient, equally with advent of DAA therapy and its good results in transplant patients, we would proceed with transplantation but after putting in place measures to ensure decreased risk of infection to recipient including counselling on transmission risk and early treatment.
If yes, how will you proceed?
MDT -Infectious disease person, Hepatologist and nephrologist to be on board.
Counsel recipient on transmission risk, effects of HCV on graft with importance of compliance to treatment.
Start DAA therapy pre transplant using a pangenomic regimen to decrease resistance and achieve quick viral suppression.
Monitor HCVRNA at 1/52 weeks,2/52 weeks,6/52 weeks and 3/12 post transplant of if LFTS get deranged, in the event we get x2 consecutive negative results, we would stop DAA and if +VE we would complete 12/52 of tx and follow up on HCV PCR until we get a viral suppression.
Consider induction with basiliximab and not ATG to get good outcomes with HCV infection and tx and equally carefully consider DI btn CNI and DAA and do appropriate dose adjustment and monitoring.
REF;
Morgan TR et al; Hep C guidance 2019,update;AASLD-IDSA recommendations for testing, managing and TX of HEP C infection. Hepatology 2020;71;686-721
2. 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 65 µmol/L. Virology was reported as follows: HBsAg negative, HBsAb negative, HBcAb negative, and both HBeAg and HBeAb are negative. HCV antibody and HCV PCR are positive. HIV is negative
– HCV Ab positive, HCV PCR positive indicates active HCV infection with a high risk of transmission
– HCV seropositivity is associated with higher all-cause graft loss and all-cause mortality
– use of HCV RNA-positive donors is no longer a major concern with the advent of DAA therapy
– an HCV RNA-positive donor can donate to an HCV RNA-positive recipient as well as to an HCV RNA-negative recipient as long as this is followed by antiviral treatment
– excellent HCV cure rates and excellent short-term graft function and safety profile have been reported
– DAA therapy should be offered in the peri-transplant period to reduce the risk of chronic HCV infection in the transplant recipient
– this potential kidney transplant recipient should be evaluated for a couple of things: –
assessment for HCV infection using HCV Ab and HCV RNA PCR
– detectable HCV RNA indicates HCV infection;
– HCV infection prior to transplantation is not a contraindication to kidney transplantation
– but if not successfully treated, it increases post-transplant morbidity and mortality
stage the liver disease: i.e.,
– assess the extent of fibrosis using blood tests (e.g., APRI score – Aspartate aminotransferase (AST)-to-platelet ratio index (APRI)) and imaging tests e.g., performing transient elastography (1)
– liver biopsy was previously considered the gold standard however, nowadays it is only performed when noninvasive test results are discordant or when liver comorbidities are suspected
– these staging tests inform on the liver-related prognosis and help guide the selection of HCV treatment regimen as well as help decide on the type of transplant to be done i.e., kidney vs combined kidney-liver transplantation
– assess for portal hypertension if there is evidence of cirrhosis
– both pre- and post- transplant antiviral DAA therapy are highly effective and safe
– there are DAAs which are pangenotypic, with established safety and efficacy in severe kidney dysfunction (eGFR <30) and even in dialysis
– decisions on the timing of antiviral therapy (i.e., pre- vs post- transplant) depends on severity of liver disease, anticipated wait time on the transplant waiting list, accessibility of organs from HCV-positive donors, extrahepatic complications of HCV infection
– pre-transplant therapy is offered to patients with advanced or rapidly progressive liver fibrosis (but not decompensated cirrhosis) or severe extrahepatic manifestations e.g., cryoglobulinemic vasculitis
– patients with decompensated cirrhosis require a liver-kidney transplant, the decision on pre- vs post- transplant DAA therapy, is individualized depending on the MELD score, access to transplantation, available treatment options, the likelihood of meaningful response to therapy and expected virologic response
– patients without decompensated cirrhosis, advanced or rapidly progressive liver fibrosis or severe extrahepatic manifestations, the treatment options depend on whether they are using a deceased donor or a living donor
– for those on the deceased-donor waiting list, the decision is informed by the anticipated waiting time – if long then pre-transplant antiviral therapy is offered
– for those using living donors, pre-transplant therapy is offered unless there are limiting factors e.g., drug-drug interactions, inability to delay the transplant for 8-12weeks to allow for DAA therapy
– timing of DAA therapy (i.e., pre- vs post- transplant) primarily depends on the waiting list advantage and the impact of delay on HCV-associated mortality especially among patients with advanced fibrosis or 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
– in kidney transplant recipients, consider the presence and extent of kidney dysfunction and the potential interactions with immunosuppressive agents
– sofosbuvir-velpatasvir is pangenotypic
monitoring post kidney transplantation
– in addition to the standard post-transplant care, 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 is an indication for 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
References
1. 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.
2. Parsikia A, Campos S, Khanmoradi K, Pang J, Balasubramanian M, Zaki R, et al. Equal 3-Year Outcomes for Kidney Transplantation Alone in HCV-Positive Patients With Cirrhosis. International surgery. 2015 Jan;100(1):142-54. PubMed PMID: 25594655. Pubmed Central PMCID: PMC4301280. Epub 2015/01/17. eng.
3. Bhamidimarri KR, Ladino M, Pedraza F, Guerra G, Mattiazzi A, Chen L, et al. Transplantation of kidneys from hepatitis C-positive donors into hepatitis C virus-infected recipients followed by early initiation of direct acting antiviral therapy: a single-center retrospective study. Transplant international : official journal of the European Society for Organ Transplantation. 2017 Sep;30(9):865-73. PubMed PMID: 28332729. Epub 2017/03/24. 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?
DBD donor with HCV antibody and PCR positive.
Yes I would accept this donor since HCV infection is not an absolute contraindication for donation.
If yes, how would you proceed?
The recipient needs to be counselled on the risk of HCV transmission and consent obtained.
The recipient HCV antibody and PCR status should be known and if positive the recipient should not have liver cirrhosis.
The recipient should have high likely hood of achieving SVR12.
The donor HCV genotyping should be done.
Post-transplant recipient could have HCV PCR done frequently starting immediate post transplant period.
Any 2 positive PCR warrants prompt initiation of DAA that are pan-genotypic after transplantation and have minimal drug interaction.
The DAA ideally should be given for 12 weeks but may be given for up to a period of 6 months.
References
UK Position Statement on the use of Organs from Hepatitis C Viraemic Donors and Increased Infectious Risk Donors in Hepatitis C Negative Recipients
This is HCV positive donation to HCV -/+ recipient , I will proceed to transplantation with DAA therapy to be administered at the time of transplant or early thereafter for 4–8 weeks is safe and effective to prevent complications of HCV infection in the recipient with excellent rates of viral clearance (SVR12) as well as excellent allograft function and survival, with excellent patient survival rates at 1 year following transplant .
Induction of immunosuppression is preferred with basiliximab over lymphocyte depleting agents ,maintenance with tacrolimus,MMF,prednisolone with drug level monitoring and follow up of viral PCR at (3,7,14 days, and 6 weeks)
.
Refrence :
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
yes, I will accept if there is a need for urgent transplantation (pt with vascular access failure or expected a long waiting list
) Or no available non-HCV donor.
If yes, how would you proceed?
-If the recipient is also HCV positive, I will assess the liver status; if the AST/platelet ratio is 0.8, I will refer to a hepatologist first to be included in MDT, and I will start DAA medications before surgery and continue post-transplant.
-if the recipient is HCV negative, I will proceed with the high risk of viral transmission with the benefit of transplant over dialysis or being on a waiting list for long time, with prophylactic initiation of DAA follow-up the LFTs, HCV PR, monitor drug-drug interactions
-the donor is better being of low or moderately high immunological risk for induction with basiliximab.
informed consent from recipient, immunosupression with Basiluximab induction and maintaince with CNI, antimetabolite and sterpod. survillance post transplant for three months and if there is any postive results start ttt with DAA
Yeas I will accept . this patient had HBsAg negative, HBsAb negative, HBcAb negative, and both HBeAg and HBeAb are negative. But he positive for HCV antibody and positive for HCV PCR. HIV is negative. Evidence shows that HCV transmission from HCV antibody positive NAT negative donor to HCV naive recipient is low. If yes, how would you proceed
Firstly council the recipient about risk of HCV infection .
For the rapidly evolving treatments for HCV have improved outcomes, and perioperative use of DAA therapy has increased the utilization of HCV- viremic donor organs.
hepatitis C treatment have led to a success rate of over 95%.
We need to check PCR for HCV in 1st,2nd week after transplantation ,6 week and 3 month ,If HCV PCR is positive, we need to start DAA within 3-10 days of positive HCV PCR and continue for 12 weeks. Then we have to follow up HCV PCR to confirm SVR, Induction therapy with basiliximab, unless patient is highly sensitized.
DAA may be necessary for up to 6 months post-transplant. References
1.Updated October 2021. Accessed November 7, 2021. 4. Global Observatory on Donation and Transplantation. International report on organ donation and transplantation activities. Executive summary 2019. http://
2. – 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
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 only if the recipient is in urgent need for a graft (those with no vascular access or those with expected very long time on waiting list) 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 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 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 in the donor 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
References
1- Utilization of HCV viremic donors in kidney transplantation: a chance or a threat?
The donor is negative for HBsAg, HBsAb, HBcAb, HBeAg and HBeAb but is positive for HCV Ab and HCV RNA by PCR. Yes, this DBD donor may be accepted for transplantation.
The latest developments in hepatitis C treatment have led to a success rate of over 95%. Most of who have been infected can now be treated using directly acting antiviral agents. It has been found that results are favorable for recipients who do not have Hepatitis C, who have received organs with hepatitis C and they were later treated and cured of the virus. Suitable donors are declined often because of the risk of transmission of hepatitis C. Using organs from such donors could be life saving.
Previously kidneys from HCV-infected donors were almost exclusively transplanted into HCV-infected patients, but with the introduction of DAA therapy, kidneys from HCV-infected organs are increasingly being transplanted into HCV-negative patients.
If yes, how would you proceed?
We have to start DAA therapy as early as possible, prior to transplant surgery. Induction agent would preferably be an agent that would not result in a pronounced replication flare of the virus. Induction would be with Basiliximab since ATG has been found to worsen the infection. Patient should receive tacrolimus, steroid and MMF. The interaction between the different DAAs and post-transplant immunosuppression medications have to be considered.
The recipient must be adequately counseled and provided with sufficient information for an informed consent. Need for dose adjustments of concomitant immunosuppressants post-transplant have to be considered by drug monitoring.
Patients must undergo testing for HCV RNA by PCR at 1st week, 2nd week, 6th week and 3 months after transplantation or if liver dysfunction occurs. If HCV PCR is negative on two subsequent testing, DAA is not needed. If HCV PCR is positive at any time, we need to start DAA within 3-10 days of positive HCV PCR and continue for 12 weeks. Then we have to follow up HCV PCR to confirm SVR. DAA may be necessary for upto 6 months post-transplant.
References:
Ghany MG, Morgan TR. Hepatitis C Guidance 2019 Update: American Association for the Study of Liver Diseases-Infectious Diseases Society of America Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection. Hepatology 2020; 71: 686-721.
For this scenario, I will accept the donation after insurance of the availability of direct anti-viral therapy and start preoperatively. We should realize that strict trials like THINKER and EXPANDER-1, although encouraging results in other trials reflecting the real world, showed an increased risk of transaminitis and higher polyomavirus infection. Attaining sustained viral response is important. Starting preoperatively will be safer and decrease the risks.
——-
√ 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. How would you proceed?
Counsel the recipient about the risk of HCV infection.
Counsel the recipient about the risk of HCV infection.
DAA at the time of Tx.
Monitor viral load post-transplantation.
SOF-base DAA regimen.
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. 4. Global Observatory on Donation and Transplantation. International report on organ donation and transplantation activities. Executive summary 2019. http:// http://www.transplant-observatory.org/wp-content/uploads/2021/06/GODT2019- data_web_updated-June-2021.pdf. Published April 2021. Accessed August 6,
Will you accept this DBD donor?Yes, I will accept this kidney donation offer if there is availability of HCV treatment post renal transplantation because:Donor is DBD. Donor’s HBV, and HIV are negative. Negative FCXM.Donor has positive HCV Ab and HCV PCR.There is high risk of HCV transmission from positive donor to negative recipient. However, transplanting kidneys from HCV positive donors to recipients with negative HCV will reduce the waiting time on dialysis and enlarge the donation pool.
If yes, how would you proceed?
1- The recipient must be counselled before transplantation about the protentional risk of HCV infection from infected donor.
2- DAA can be started either before transplantation or after transplantation depending on centers protocols. 3- Start DAA (Glecaprevir/Pibrentasvir) pre-operatively then daily for 7 days. 4- Recipient follow up of HCV PCR: at 3-7 days then at day 14 then at 6 weeks. If HCV PCR is negative, DAA is not needed If HCV PCR is positive at any time, start DAA within 3-10 days of positive HCV PCR and continue for 12 weeks. Then follow HCV PCR to confirm SVR. 5- Induction immunosuppression: Basiliximab (IL2R) , try to avoid ATG or Almetuzumab. 6- Follow up with infectious disease and hepatology team to monitor for liver cirrhosis, liver cell failure, portal hypertension.
· 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.
If yes, how would you proceed?
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.
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.
If yes, how would you proceed?
1. I would proceed if the followings are met:
a. Donors do not have cirrhosis.
b. 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).
2. In such situation, I will initiate DAAs in the early post-transplant period.
3. HCV PCR to be checked in the post-transplant period at day3-day7 – day10 -day14 and 6weeks post-transplant.
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.
The donor with HCV viremia can be accepted to reduce the risk of long waiting time. However, we need to start antiviral treatment immediately to prevent viral transmission as it was shown that it is almost 100% without treatment.
However, given the significant survival benefit from transplant, HCV-viremic to HCV-naive transplant with concomitant DAA therapy can improve outcomes for patients with ESRD because transmission can be prevented by prophylactic DAA therapy and there is a high cure rate for post-transplant patients with established infection. A multicenter open-label trial of 30 patients who received glecaprevir-pibrentasvir therapy started within 3 days of HCV viremic kidney transplant and continued for 8 weeks. All patients achieved SVR and no severe adverse events were deemed related to HCV infection or glecaprevir-pibrentasvir
therapy. Taken together, these data demonstrate that the best patient outcomes are obtained with prophylactic DAA or DAA therapy initiated shortly after transplant.
If yes, how would you proceed?
Counselling the recipients about risk and benefit and treatment plan.
Will give glecaprevir-pibrentasvir therapy started within 3 days of HCV viremic kidney transplant and continued for 8 weeks.
Induction therapy with basiliximab, unless patient is highly sensitized.
Close monitoring of his liver function, coagulation profile, HCV PCR.
Involvement of hepatologist and clinical pharmacist. Close monitoring of kidney function, tacrolimus level for the potential of drug interaction.
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 will accept this donor.
If yes, how would you proceed?
I shall start monitoring HCV RNA PCR soon after transplantation
If positive, I will use one of the following option: ledipasvir/sofosbuvir, velpatasvir/sofosbuvir and glecaprevir/pibrentasvir
Sustained virological response can be seen in most patients
But there is an important caveat that what is the dire emergency of accepting an infecting organ.
REF:
Zhang Jinwei, Tan Weilong, Wang Chunhui, Chen Qiong, Shen Chao, Fan Haozhi, Zhang Yun, Huang Peng, Yue Ming. Efficacy and Safety of Direct-Acting Antivirals in Kidney Transplantation From HCV-Viremic Donors to Negative Recipients: A Meta-Analysis. Frontiers in Medicine. vol.9, 2022. DOI=10.3389/fmed.2022.802686
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
Jandovitz N, Nair V, Grodstein E, Molmenti E, Fahmy A, Abate M, Bhaskaran M, Teperman L. Hepatitis C-positive donor to negative recipient kidney transplantation: A real-world experience. Transpl Infect Dis. 2021 Jun;23(3):e13540. doi: 10.1111/tid.13540. Epub 2021 Jan 9. PMID: 33259125.
HBsAg negative, HBsAb negative, HBcAb negative, both HBeAg and HBeAb are negative. HCV antibody and HCV positive. HIV negative.
The donor is HCV positive with HCV antibodies. I would accept this donor if there is no other suitable donor available in the immediate future. The lifespan and quality of life of the recipient only worsens day by day on the waitlist while receiving regular dialysis.
Evidence shows that HCV transmission from HCV antibody positive NAT negative donor to HCV naive recipient is low. However, our donor does not come under this category.
The combination of donor’s antibody and NAT status provides an understanding of the chronicity and transmissibility of their infection. NAT provides an accurate assessment of HCV risk of transmission from transplantation.
HCV antibody positive NAT positive donors pose a higher risk of disease transmission to the recipient. The recipient will most probably become viremic after transplant and will need anti viral therapy. However, in 12 weeks, it is possible to find that our recipient is virus free with undetectable HCV RNA levels. The patient also has a high chance of good graft function with less risk of graft loss or mortality of the patient.
I would accept this donor provided the recipient has given full informed consent.
Proceeding with transplant
The important aspect to consider for good outcome is to give sufficient antiviral prophylaxis post transplant to the recipient. DAA will be administered to the recipient immediately post transplant with close monitoring of drug levels of IS regimen. Induction would be with Basiliximab since ATG has been found to worsen infection. Patient will receive triple IS regimen – tacrolimus, steroid and MMF. Monitoring of drug levels is essential since DAA can cause fluctuations in IS drug levels leading to either insufficient immunosuppression, thereby increasing risk of graft rejection, or too much immunosuppression, increasing risk of infection and toxicity of IS drugs.
References
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.
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:e927532-1-e-927532-4. doi: 10.12659/AJCR.927532
Steiner S, Raguž-Lučić N, Erceg D. Direct-Acting Antivirals (DAAs): Drug-Drug Interactions (DDIs) in the Treatment of Hepatitis C Virus (HCV). Update on Hepatitis C [Internet]. 2017 Oct 4; Available from: http://dx.doi.org/10.5772/intechopen.70788
⭐ ⭐ ⭐ Accepting HCV postive donor for HCV naive recipient could be accepted in case of long waiting time on dialysis (transplantation from HCV viremic organs has better survival than dialysis).
⭐ but only after counseling, obtaining consent, starting preemptive antiviral in the day before transplantation and for 3 months until achieving SVR with EBR_GZR.
_ no available data about immunological risk , cross match and HLA mismatch or blood group. But, I will use induction with basiliximab if no immunological risk to prevent flaring up of viremia.
-Yes ,as DAAT availability improves the outcome with high rate of HCV cure
– MDT have to be involved including a virologist and hepatologist
The recipient either HCV positive or negative has to be informed about the donor status and sign the HCV specific consent.
This donor has HCV RNA positive and HCV Ab positive denoting HCV viremia with risk of HCV infection transmission therefore pangenotypic agents for long or intermediate post-transplant durations can lead to favourable outcomes
The recipient have to be monitored for HCV viraemia at postoperative day3receive DAAT immediately post transplant for 12 weeks with following SVR 12 ,immunosuppression given have to be closely monitored to avoid drug -drug interaction .
Gupta et al used a trial design using 2-4 doses of pangenotypic SOF and Velpatasvir (VEL) on transplant day 0–4, immediately started pre-transplant to prevent transmission in 50 recipients. 6 cases across all phases of the study required 3 months of DAA treatment for HCV transmission. This regimen was associated with a lower SVR12 compared to other trials (98%).
Current induction and maintenance immunosuppressives can be used in HCV-infected kidney transplant recipients
Reference
-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.
– Chow K. M. KDIGO GUIDELINES TREATMENT OFHCVINKIDNEY TRANSPLANT RECIPIENTS
Will you accept this DBD donor? In this case the donor is HCV antibody and HCV PCR are positive. Yes I will accept him for kidney donation as the outcomes are still superior to staying on long term dialysis. If Recipient is HCV negative then detailed counselling is required. In such scenario, HCV PCR should be done at week1 , Week 2 and Week 6. HVC PCR Negative- No action , only reassurance HVC PCR Positive- Start DAA within one week of positive test till SVR is achieved . If recipient is HCV positive , I will start DAA early after transplant.
If yes, how would you proceed? Patient has to be counselled in detailed about the potential infected organ. I will counsel him about graft survival , outcomes and mortality . I will explain that transplantation in such situation is superior to dialysis or staying on waiting list. DAA has to be started 3 days post transplant. In such scenarios it will be sensible to avoid ATG Triple immune suppression with TAC, MMF and Prednisolone. Frequent monitoring of drug levels and adjusting the doses I will be vigilant about drug interactions which may change drug levels and pose risk of rejection.
Also a monitoring is required for infections, malignancy an drisk of recurrence of primary disease. Salvadori M, Tsalouchos A. Hepatitis C and renal transplantation in era of new antiviral agents. World J Transplant. 2018 Aug 9;8(4):84-96. Jandovitz N, Nair V, Grodstein E, Molmenti E, Fahmy A, Abate M, Bhaskaran M, Teperman L. Hepatitis C-positive donor to negative recipient kidney transplantation: A real-world experience. Transpl Infect Dis. 2021 Jun;23(3):e13540. KDIGO The 2022 Hepatitis C in CKD Guideline
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 as well as positive HCV RNA PCR.
The scenario implies an untreated or partially treated (if known HCV infection previously) HCV infection (1).
The HCV status of the recipient has not been provided. Nevertheless, I will accept this donor, after counselling the recipient, and if the prospective recipient agrees for post-transplant surveillance required in this scenario as well as there is availability of directly acting antivirals (DAAs), if needed (2). HCV positive donors can be accepted regardless of the HCV status of the potential kidney transplant recipient (1).
In case the recipient is HCV negative, then post-transplant, the recipient should be tested for HCV RNA PCR (2). The HCV RNA PCR 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 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 and HCV viremic, 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, Hepatitis B virus infection assessment, 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 (3).
Donor evaluation: The prospective donor who is positive for anti-HCV antibodies as well as HCV RNA PCR, 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. The DAA treatment of the donor can be delayed if the recipient requires transplant urgently due to reasons like poorly tolerating dialysis, or poor vascular access (1).
In the index scenario, as the live donor is HCV RNA PCR positive, it is preferable to treat with DAA prior to donation. 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 pre-transplant if the expected transplant will take place after more than 24 weeks (3). If there is urgency (poor vascular access, patient not tolerating dialysis), or if the transplant is expected in less than 24 weeks (12 weeks of therapy and 12 weeks of follow-up for SVR12), then the transplant can be proceeded with and the treatment of the recipient using DAAs can be done in the immediate pre-transplant or early post-transplant period (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.
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.
the donor has positive HCV antibody and HCV RNA PCR is also Positive, a case of active HCV infection. Because of treatment option availability for R- patient who gets a D+ organ would be more cost effective and improve survival as compared to HD.
We urge that kidneys from HCV-infected donors be considered for transplantation independent of the HCV status of the prospective recipients.
If yes, how would you proceed?
DAA treatment should be started as soon as possible after transplantation. Therefore, DAA treatment options should be discussed with recipient and relevant pros and cons discussed.
obtain informed consent before performing kidney transplants involving donors infected with HCV and recipients who are not infected with HCV.
DAA chooses according to the genotype (if available). If not available, use pan-genotypic treatment.
Induction with basiliximab would be good option but event ATG if needed can be given.
continue routine immunosuppressive medication (tacrolimus, MMF, and prednisolone), and needs regular drug level monitoring with close watch on rejection
Ideally, HCV PCR should be repeated at 3,7,14 days, and 6 weeks after therapy.
References:
KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease. Kidney Int. 2022.
Ronit Patnaik, MD, Eugenia Tsai. Hepatitis C Virus Treatment and Solid Organ
Will you accept this DBD donor?
Yes, I will accept (although this is active HCV infection with high risk of transmission) provided that:
1. Patients have an access to DAA therapy
2. Comprehensive HCV monitoring
3. National/local regulations permit it
4. Specific comprehensive informed consent
5. Close follow-up to capture complications
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
Transplantation of HCV-viremic organs into HCV-naive recipients followed by the use of DAA agents provides excellent patient and allograft survival. Securing DAA therapy post-transplant is essential and patients should be fully informed of the associated risks, including the potential of HCV treatment failure
Risks of HCV D+ to R- transplantation:
1. fibrosing cholestatic hepatitis (FCH). It is an aggressive form of HCV recurrence seen in 1.5% in kidney transplant
2. infection transmission (DAA therapy results a high cure)
3. DAA treatment failure (<5%)
4. Extra-hepatic manifestations of HCV (cryoglobulinaemic vasculitis) or PTLD
5. Sexual transmission of HCV to a partner [(extremely low (<2% perhaps)]
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
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 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.
This is a Hepatitis C viremic DBD donor who is hepatitis B negative
He has a normal creatinine and the cause of death SAH
I would accept this donor
The preferred recipient would be a hepatitis C positive recipient
If there would be no hepatitis C positive recipient, we can select a hepatitis C negative recipient after counseling and getting informed consent
We should involve a hepatologist who has experience in treating HCV
More history about the donor should be sought – especially if there was a history of previous treatment as that suggest resistant genotype of HCV
The HCV genotying should be done although results would take a few days and the donor center should communicate the results to the recipient center
The HCV negative recipient should have HCV RNA monitored after 3-7 days, then after 10 – 14 days then 6 weeks. If the HCV RNA turns positive, a second HCV PCR should be done. The patient should be treated with Direct Acting Antiviral Agents which are pangenotypic and it should be started within 3 – 10 days of the results of the first HCV PCR test.
The patient should be treated for 12 weeks and during that period the tacrolimus levels should be monitored
If after six weeks, the HCV RNA is remains negative, then there is no need for further testing
UK Position Statement on the use of Organs from Hepatitis C Viraemic Donors and Increased Infectious Risk Donors in Hepatitis C Negative Recipients
deceased donor with HCV with PCR positive is an increased risk of HCV infection in the recipient, also increasing morbidity and mortality.
counseling the recipient about the risk of infection, the medical needs outweigh the risk of infection, and sharing the patient in the decision.
2018 KIDIGO guidelines recommended that kidneys from HCV seropositive and RNA positive donors should only be given HCV RNA positive recipients, however, data demonstrate the safety of Transplant kidneys from HCV RNA positive donors to HCV negative recipients early or pre-emptive with DAA
do lad urine for haematuria or proteinuria and KFT
If yes, how would you proceed?
if the recipient after counseling,he accepts the transplant for HCV
for the deceased donor do KFT, urine for hematuria and proteinuria
pre-emptive DAA treatment and follow-up by PCR HCV,LFT,liver enzyme
references
uptodate
kidigo 2018
Our donor is HBsAg negative, HBsAb negative, HBcAb negative, and both HBeAg and HBeAb are negative. HCV antibody and HCV PCR are positive. HIV is negative. Will you accept this DBD donor?
Yes, I will accept.
My argument based on many points :
1- HCV-seropositive patients lived longer with transplantation (aHR at 3 years, 0.42; 95% CI, 0.27-0.63) compared to remaining on the waitlist.(1)
2- Treatment of HCV recipient with DAA with high curable rate before or after transplantation(2).
3- Studies shown great result in outcome, some shown no recipient became infected with chronic HCV with DAA treatment (3). If yes, how would you proceed?
1-Recipients monitored for HCV viremia starting at postoperative day 3.
2- Once HCV RNA detected: elbasvir–grazoprevir (Zepatier) treatment for 12 weeks and following the response.
3-Basiliximab induction is favored over ATG for induction.
3-We should closely observe immunosuppression levels, to avoid drug-drug interactions. References:
1-Sawinski D, Forde KA, Lo Re V 3rd, Goldberg DS, Cohen JB, Locke JE, Bloom RD, Brensinger C, Weldon J, Shults J, Reese PP. Mortality and kidney transplantation outcomes among hepatitis C virus-seropositive maintenance dialysis patients: a retrospective cohort study. Am J Kidney Dis 2019;73:815-826.
2-KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease. Kidney Int. 2022
3-Durand CM, Bowring MG, Brown DM, Chattergoon MA, Massaccesi G, Bair N, Wesson R, Reyad A, Naqvi FF, Ostrander D, Sugarman J, Segev DL, Sulkowski M, Desai NM. Direct-acting antiviral prophylaxis in kidney transplantation from hepatitis C virus–infected donors to noninfected recipients: an open-label nonrandomized trial. Ann Intern Med 2018;168:533-540.
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.
If yes, how would you proceed?
asking for U&A for protenuria and heamturia for the donor exculding that he has a renal nephropatht assciated with hep C, like cryo , MPGN and membranous nephropathy.
Donor kidneys with HCV infection are accepted for donation, regardless of the HCV status of the recipients. I shall therefore accept the patient.
As there is a high risk that the recipient of the kidneys from HCV Ab +/ HCV PCR+ donors would develop the hepatitis C virus, I will accept the patient’s kidneys provided DAA is available. When transplanting HCV-infected kidneys into HCV-uninfected recipients, transplant hospitals must instruct and notify their patients. Patients need to be aware of the advantages and disadvantages of HCV-infected kidney transplantation, including DAA therapy.
Transplant centers should check DAA availability for early post-transplantation when kidneys are donated by HCV positive to HCV negative.
If yes, how would you proceed?
With the purpose of lowering the risk of HCV-related liver damage, DAA should be begun as soon as possible after transplantation.
If available, the DAA regimen is chosen in accordance with the viral genotype. Whenever possible, adopt pan-genotypic therapy. Although the timing of antiviral medication is universal, it is advised to start it as soon as possible after transplant.
Basiliximab induction is favored over ATG for induction.
Tacrolimus, MMF, and prednisolone used as a maintenance immunosuppressive drug with regular trough level monitoring. HCV PCR testing should be done often along with drug administration (3,7,14 days, and 6 weeks).
Yes, this donor can be accepted after counselling the recipient and ensuring the availability of DAA therapy as the cumulative risk of remaining on waiting list or dialytic support is worse when compared to undergoing renal transplantation.
Initiation of prophylactic therapy combining DAA with ezetimibe right before transplantation up to 7 days course can reduce the probability of viral infection.
Special emphasis would be on the type of DAA therapy that causes less interactions with immunosuppressive agents. The use of induction therapy must be cautious with offering better matching is considered the best.
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 assess hepatic tissue status ,decide the best choice of DAAs therapy until obtaining HCV PCR below detection level two or three times ,renal transplantation can be done safely afterwards.
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.
A 56-year-old male DBD donor had SAH (grade 5) complicating cerebral aneurysm, S Cr was 65 µmol/L, HBsAg negative, HBsAb negative, HBcAb negative, HBeAg negative, HIV negative. HCV antibody and HCV PCR positive, Will you accept this DBD donor? Yes, I will accept this patient kidneys if there is availability of DAA as there is high risk of
transmitting hepatitis C virus infection in the recipient from HCV Ab +/ HCV PCR+
donors.
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
If yes, how would you proceed?
HCV Ab +ve Donor, HCV PCR +ve Donor TO HCV-ve Recipient:
Will 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.
HCV HCV Ab +ve Donor, HCV PCR +ve Donor TO HCV +ve Recipient:
MDT For GIT Evaluation of recipient to grade the fibrosis (fibro scan or liver biopsy),
portal hypertension.
Start DAA before or early after transplantation.
Safely Use Induction with Basiliximab(Simulect) :
IL2R as an induction agent avoid ATG/Alemtuzumab if possible. References:
Lecture of Professor May Hassaballah in HCV and kidney transplant
KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease. Kidney Int. 2022.
yes I will accept the donor but there is high risk of transmitting HCV infection
donor testing for Genotype
we should take consent to receive a HCV D+ organ and patient should receive education regarding the risk of transmitting the infection and need for Treatment after transplant
patient should be seen by liver specialist
monitor of HCV PCR post transplant day 3-7. If negative then day 10-14 if negative 6 week post transplant if negative then manage as standard recipient
At any time positive PCR Start DAA within 3-10 working days of frist positive PCR
KDIGO guideline TREATMENT OF HCV IN KIDNEY TRANSPLANTRECIPIENTS Position Statement on the use of Organs from Hepatitis C Viraemic Donors and Increased Infectious Risk Donors in Hepatitis C Negative Recipients (BTS)
if the patient on prolong waiting list and have no chance fr getting donor easily ….. yes i accept after counseling and starting anti HCV traetment for 3 months with close monitoring
Will you accept this DBD donor? Yes, I will accept this patient kidneys if there is availability of DAA as there is high risk of transmitting hepatitis C virus infection in the recipient from anti HCV+/PCR+ donors.
If yes, how would you proceed? HCV+ve D, HCV PCR+ve D/HCV-ve R 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.
HCV+ve D, HCV PCR+ve D/HCV+ve R
Need hepatologist evaluation of recipient for the grade of fibrosis (fibro scan or liver biopsy), portal hypertension. Start DAA before or early after transplantation. See drug interaction. IL2R as an induction agent avoid ATG/alemtuzumab if possible. 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.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.
Yes, the donor has been found to have positive levels of HCV antibody and HCR RNA.
This indicates that he has an active case of HCV infection.
A course of treatment to cure an R- patient who was to get a D+ organ would be less expensive than the cost of one year’s worth of dialysis
We urge that kidneys from HCV-infected donors be considered for transplantation independent of the HCV status of the prospective recipients of kidney transplants
If yes, how would you proceed?
To lessen the likelihood of developing a liver disease caused by HCV, DAA treatment should be started as soon as possible after transplantation. As a result, obtaining DAA treatment through contacts with insurance companies before moving forward with the transplant operation is an important component of the process.
Transplant centers are required to guarantee that patients get an education and are involved in conversations with adequate information to obtain informed consent before performing kidney transplants involving donors infected with HCV and recipients who are not infected with HCV.
Patients should be advised of the risks and advantages of receiving a transplant with an HCV-infected person, including the need for DAA therapy if they choose to proceed with the procedure.
Transplant hospitals should make sure that DAAs are available for early post-transplant treatment.
DAA chooses according to the genotype (if available). If not available, use pan-genotypic treatment.
Induction with basiliximab(as long as no indication for ATG)
continuous immunosuppressive medication (tacrolimus, MMF, and prednisolone), regular drug level and rejection monitoring, and HCV PCR (3,7,14 days, and 6 weeks).
References:
KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease. Kidney Int. 2022.
Ronit Patnaik, MD, Eugenia Tsai. Hepatitis C Virus Treatment and Solid Organ
DBD donor with anti HCV Ab +/ HCV PCR +ve , negative HBV serology and Negative HIV.
Will you accept this DBD donor?
Yes, I will accept this patient kidneys, given the favorable outcomes, than being for long time on dialysis and transplant waiting list with a proposed 68% mortality reduction. Whatever the HCV status of the recipient. In HCV-ve 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. In HCV+ve recipients I would start DAA therapy before or early after transplantation. If yes, how would you proceed? I will discuss the issue of having a HCV infected organs, with the recipient and the overall outcomes, graft survival and mortality, and how this practice is approved lastly by evidence and better than being on dialysis, or for long time on waiting list, and the availability of new drugs DAA with sustained viral response reaching 100%. The options for the recipient are: · Prophylactic initiation of antiviral therapy 12 hours before transplantation for 7 days (glecaprevir/pibrentasevir and ezetimibe). · Initiation of DAA immediately after transplantation- EXPANDER-1 trial. · Initiation of DAA with onset of viremia- 3 days after transplantation- THINKER tria.-elbasvir/grazoprevir I will try to avoid the use of ATG and use of less drug-drug interaction maintenance immunosuppressive therapy( tacrolimus+MMF+prednisolone) with frequent monitoring of drug level and monitor for rejection, the long term risk of infection, malignancy, and recurrence of primary renal disease more seen in HCV infected recipients. References: (1) Roth D, Gaynor JJ, Reddy KR, Ciancio G, Sageshima J, Kupin W, Guerra G, Chen L, Burke GW 3rd. Effect of kidney transplantation on outcomes among patients with hepatitis C. J Am Soc Nephrol. 2011 Jun;22(6):1152-60. doi: 10.1681/ASN.2010060668. Epub 2011 May 5. PMID: 21546575; PMCID: PMC3103735. (2) 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. (3) Baid-Agrawal S, Pascual M, Moradpour D, Somasundaram R, Muche M. Hepatitis C virus infection and kidney transplantation in 2014: what’s new? Am J Transplant. 2014 Oct;14(10):2206-20. doi: 10.1111/ajt.12835. Epub 2014 Aug 4. PMID: 25091274. 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.
Given the option of receiving kidneys from a male DBD (donor after brain stem death) donor who was 56 years old and had a grade 5 SAH complicated a cerebral aneurysm.
His S Cr upon retrieval was 65 mol/L.
According to reports on virology:
HBeAg, HBeAb, and HBcAb are all negative, as well as HBsAg and HBsAb. Both the HCV PCR and HCV antibody are positive.
HIV is absent.
Yes I will precede transplant with this donor
Excellent viral, allograft, and patient outcomes are linked to kidney transplantation from HCV-infected donors to uninfected recipients with prompt or early DAA treatment
HCV-infected kidney transplantation into HCV-uninfected patients is a cost-effective (and frequently cost-saving) approach that enhances clinical results.
Based on the evidence supporting the increased use of organs from HCV-infected DD-like IVDA donors with early use of DAA therapy that provides a high cure rate and well-tolerated course, we can still accept kidneys from HCV-infected donors to potential recipients Further management
Informed consent and explaining for future risk and benefit for HCV positive donor
Obtaining an HCV-infected kidney depends on a number of variables, including the availability of DAA, the length of the wait, and the organ’s quality.
Throughout the first four weeks of the complete 12-week treatment period, early DAA medication is preferred before or right after transplantation, with frequent HCV PCR monitoring until reaching SVR.
And also need frequently monitoring of HCV infection post transplant for active infection and its complication.
Drug- drug interaction with DAA and immunosupression and also need to monitor their side effect
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.
HCV-Infected Deceased Donor Kidney Transplantation-Time to Take Up the Offer Yuvaram N V Reddy 1 , Krishna P Reddy 2 , Meghan E Sise 3
Hepatitis C Virus Treatment and Solid Organ Transplantation # Ronit Patnaik, and Eugenia Tsai,
A NAT-positive (viremic) HCV-seropositive donor has an active infection & carries a significant risk for disease transmission.
Shortage of donor supply has dictated the use of high-risk donors such as those who are HCV positive.
Donor kidneys with HCV infection have not been used as much in the past. Yet, research has shown positive long-term results & the availability of DAA therapy & its use around the time of TX reduces the risk of chronic HCV infection in the recipient & thus has led to the recent rise of TX of kidneys from HCV-infected donors into HCV-naive recipients.
=============================== 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 also accept this donor in the mentioned setting.
KTX is recommended as the best therapeutic option for patients with CKD G5 irrespective of presence of HCV infection (1A) (KDIGO HCV Guideline).
It is suggested that if receiving a kidney from an HCV-positive donor improves the chances for transplantation, the HCV NAT-positive patient can undergo transplantation with an HCV-positive kidney & be treated for HCV infection after transplantation (2B). (KDIGO HCV Guidelines)
Current practice in the UK is to restrict the use of HCV D+ organs to HCV positive recipients (R+), although this is predominantly accepted in the field of liver transplantation.
Conditions which should be met:
The recipient should be evaluated for severity of liver disease & presence of portal hypertension (if indicated) prior to acceptance for KTX (2D) (KDIGO HCV Guidelines).
If compensated cirrhosis (without portal hypertension) is diagnosed in the background of HCV infection, isolated KTX is recommended (1B). (KDIGO HCV Guidelines).
If decompensated cirrhosis is diagnosed, the patient should be referred for combined liver-kidney transplantation (1B) HCV treatment deferred until after transplantation (1D) (KDIGO HCV Guidelines).
Timing of HCV treatment in relation to KTX (before vs. after) should be based on donor type (LD vs. DD), waitlist times by donor type, center-specific policies governing the use of kidneys from HCV-infected DDs, HCV genotype, & severity of liver fibrosis (Not Graded) (KDIGO HCV Guidelines).
DAA therapy recommended either before or after transplantation (1A) (KDIGO HCV Guidelines).
Candidates with HCV with a living kidney donor can be considered for treatment before or after transplantation according to HCV genotype & anticipated timing of transplantation (2B). (KDIGO HCV Guidelines)
References
Chadban, Steven J. et al., KDIGO Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation. Transplantation 104(4S1):p S11-S103, April 2020. | DOI: 10.1097/TP.0000000000003136
Yes, the serological data of the donor; HCV Ab positive and PCR positive would suggest active infection & high risk of transmission. Nonetheless these are not absolute contraindication for transplantation given the availability and the efficacy of the current DAA therapy in eradication of HCV infection. In past, one would have discarded this organ but this is not the case now days.
The ideal scenario is to give this kidney to HCV positive recipient. However, HCV negative recipient can also be in a position to get this kidney to avoid long waiting list and mortality. This recipient needs to be counsel about the risk of contracting HCV and at the same time the chance treatment and cure of the virus by DAA therapy. In case of a recipient with HCV, exclusion of liver cirrhosis or HCC as well as as co-infection with HBV is essential before transplantation
DAA should be started early at the time of transplantation to reduce the risk of HCV-related liver disease. Therefore, securing DAA therapy through communications with the insurance companies before to proceed of essential part of the transplant procedure. This patient has a chance to achieve SVR12 which will minimize the risk of HCV infection
Reference:
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
2. 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 65 µmol/L. Virology was reported as follows: HBsAg negative, HBsAb negative, HBcAb negative, and both HBeAg and HBeAb are negative. HCV antibody and HCV PCR are positive. HIV is negative
=================================================================== History
A 56-year-old male DBD donor had SAH (grade 5) complicating cerebral aneurysm, S Cr was 65 µmol/L, HBsAg negative, HBsAb negative, HBcAb negative, HBeAg negative, HCV antibody and HCV PCR positive, HIV negative.
Organ donation can save up to eight lives and improve many more, but the organ transplant waiting list continues to increase.
Using HCV-positive donor organs in HCV-negative patients has both benefits and drawbacks, such as minimizing mortality and patient wait times, but also having a high risk of 100% HCV transfer.
HCV-positive donors and HCV-negative recipients receiving organ transplants, as well as DAA therapy outcomes.
Will you accept this DBD donor?
Yes I will accept this donor .
If yes, how would you proceed?
The working party recommended standardized, longitudinal testing for hepatitis C RNA of the recipient following receipt of either a HCV antibody positive graft, a HCV RNA positive graft or a graft from an increased infectious risk donor.
Patients with HCV can be treated effectively and safely pre-transplantation with DAA if they have genotypes 1 or 4.
Where treatment with elbasvir/grasoprevir of HCV+ patients with a GFR <30 mL/min afforded a 99% cure rate and similar rates of adverse events between the placebo and study groups.
In addition to elbasvir/grasoprevir, drug development continues to advance and it is anticipated that in the near future, DAAs will become available for all genotypes.
DAA has been successful in treating HCV post-transplantation, with cure rates close to 100%. However, calcineurin inhibitor levels may be affected.
Hepatitis C and Kidney Transplantation: Past, Present, and FutureAugust 14, 2017 by AJKD
Veroux, M., Corona, D., Sinagra, N., Giaquinta, A., Zerbo, D., Ekser, B., Giuffrida, G., Caglià, P., Gula, R., Ardita, V., & Veroux, P. (2014). Kidney transplantation from donors with hepatitis C infection. World journal of gastroenterology, 20(11), 2801–2809. https://doi.org/10.3748/wjg.v20.i11.2801
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.
I would accept the donor if transplantation is urgently indicated as in case of exhausted vascular access availability. In this case two approaches are advocated in Thinker and Expander II studies which are either to start DAA therapy right before transplantation and continue thereafter. or observe and follow up closely for infection transmission , then to commence DAA.
If there is no urgency in transplantation then proper treatment of the donor to achieve SVR for 6-12 months before proceeding with transplantation.
Reference:
1]Pagan et al. Should my patient accept a kidney from a hepatitis C virus-infected donor?.Kidney 360 1[2] :p127-129,Feb 2020
Will you accept this donor and how would you proceed?
The donor is both HCR RNA and HCV antibody positive.That means he has active HCV infection.”A course of therapy to cure a R- patient receiving a D+ organ would be less than the cost of dialysis for one year”KDIGO guidelines on HCV (2022) mention that –
“We recommend that kidneys from HCV-infected donors be considered regardless of 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 transplantation with an HCV infected kidney, including the need for DAA treatment (Not Graded).When transplanting kidneys from HCV-infected donors into HCV-uninfected recipients, transplant centers should confirm availability of DAAs for initiation in the early post-transplant period (Not Graded)BTS guidelines mention that :
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.UK Position Statement on the use of Organs from Hepatitis C Viraemic Donors and Increased Infectious Risk Donors in Hepatitis C Negative Recipients
Interpretation this Case according virology report: HBsAg / HBsAb / HBcAb / HBeAg / HBeAb –—– (negative) HCV Ab (positive) / HCV PCR (positive) HIV (negative)
This patient is negative to (HBV& HIV) but this patient has (HCVAb&PCR positive) My impression;
(Active HCV infection with high transmission risk). 1-Will you accept this DBD donor? Yes; I will accept this DBD donor
-Prior to 2014, kidneys from HCV-infected donors were almost exclusively transplanted into HCV-infected patients.
-This was due to the limited treatment options, and the increased risk of death, graft loss, and severe liver disease compared with HCV recipients who received kidneys from HCV-negative donors.
-However, with the advent of DAA therapy, and the rapid increase in the number of deceased donors infected with HCV in some parts of the world due to the opioid epidemic, kidneys from HCV-infected organs are increasingly being transplanted into HCV-negative patients. According KDIGO-2022 guidelines;
-Kidney transplantation Is the best therapeutic option for patients with CKD G5 irrespective of presence of HCV infection. (1A)
-Kidneys from HCV-infected donors be considered regardless of HCV status of potential kidney transplant recipients. (1C) 2-If yes, how would you proceed? Keep in mind; -Short term outcomes, -Incidence of CMV and BK viremia higher than expected in HCV negative recipients,
-All HCV-negative patients received formal education about the risks and unknowns of being transplanted with a kidney from an HCV-infected donor, and this practice, along with a formal informed consent process, must be part of any protocol that involves transplanting kidneys from HCV-infected donors into HCV-negative patients.
-Because the only reported cases of fibrosing cholestatic HCV in the setting of transplanting kidneys from HCV-infected donors into HCV-negative recipients occurred with delayed initiation of therapy (two of the cases were >80 days post-transplant), it is recommended to start DAA therapy as early as possible,
-The interaction between the different DAAs and transplant immunosuppression,
-Management of HCV-related complications in kidney transplant recipients. For proceeding HCV infected donor: I will follow KDIGO Guidelines; – 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 transplantation with an HCV-infected kidney, including the need for DAA treatment. (Not Graded)
-When transplanting kidneys from HCV-infected donors into HCV uninfected recipients, transplant centers should confirm availability of DAAs for initiation in the early-post transplant period. (Not Graded)
-However, there are insufficient data to determine the exact time point at which DAA therapy should be started (e.g., 3 days vs 7 days vs 28 days).
-Kidney transplant recipients being treated with DAAs be evaluated for the need for dose adjustments of concomitant immunosuppressants. (1C)
-Patients previously infected with HCV who achieved SVR before transplantation undergo testing by NAT 3 months after transplantation or if liver dysfunction occurs. (2D)
-Kidney transplant recipients with cirrhosis should have the same liver disease follow-up as non-transplant patients, as outlined in the American Association for the Study of Liver Diseases (AASLD) guidelines. (Not Graded)
-HCV-infected kidney transplant recipients should be tested at least every 6 months for proteinuria. (Not Graded).
-Patients who develop new-onset proteinuria (either urine protein-creatinine ratio > 1 g/g or 24-hour urine protein > 1 g on 2 or more occasions) have an allograft biopsy with immunofluorescence and electron microscopy included in the analysis. (2D)
-Treatment with a DAA regimen in patients with post-transplant HCV-associated glomerulonephritis (1D). References:
-Mandal AK, Kraus ES, Samaniego M, et al. Shorter waiting times for hepatitis C virus seropositive recipients of cadaveric renal allografts from hepatitis C virus seropositive donors. Clin Transplant 2000; 14: 391-396.
-Goldberg DS, Abt PL, Blumberg EA, et al. Trial of Transplantation of HCV-Infected Kidneys into Uninfected Recipients. N Engl J Med 2017; 376: 2394-2395.
-Durand CM, Bowring MG, Brown DM, et al. Direct-Acting Antiviral Prophylaxis in Kidney Transplantation From Hepatitis C Virus-Infected Donors to Noninfected Recipients: An Open-Label Nonrandomized Trial. Ann Intern Med 2018; 168: 533-540.
-Reese PP, Abt PL, Blumberg EA, et al. Twelve-Month Outcomes After Transplant of Hepatitis C-Infected Kidneys Into Uninfected Recipients: A Single-Group Trial. Ann Intern Med 2018; 169: 273-281.
-Molnar MZ, Nair S, Cseprekal O, et al. Transplantation of kidneys from hepatitis Cinfected donors to hepatitis C-negative recipients: Single center experience. Am J Transplant 2019; 19: 3046-3057.
-Ghany MG, Morgan TR. Hepatitis C Guidance 2019 Update: American Association for the Study of Liver Diseases-Infectious Diseases Society of America Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection. Hepatology 2020; 71: 686-721.
Thankyou actually in such a scenario PCR tests are started as early as :
day3-day7 if -ve then
day10 -14 if -ve
6 weeks
in a +ve PCR start DAA within 3-10 days.
some centers would start prophylactically from day0.
Will you accept this DBD donor?
Kidney transplantation from HCV-infected donors to uninfected recipients with immediate or early DAA treatment is associated with excellent viral,
allograft, and patient outcomes (1).
transplanting HCV-infected kidneys into HCV-uninfected recipients is a cost-effective (and often cost-saving) strategy that improves clinical outcomes (2).
So, the answer is Yes, still we can accept the Kidneys from HCV-infected donors to potential recipients based on the available evidence supporting the increased use of organs from HCV-infected DD-like IVDA with early use of DAA therapy that provides a high cure rate and well-tolerated course, also the recipient should receive education and involved in discussion with the necessary information to provide informed consent. Patients should be up-to-date on the risks and benefits of transplantation with an HCV-infected kidney, including the need for DAA treatment, and assuring the availability of the DAA therapy once indicated after transplantation.
If yes, how would you proceed?
Getting an HCV-infected kidney is dependent on factors such asavailability of DAA, wait for time, and quality of the organ
Early DAA therapy is preferred before or immediately after transplantation within the first 4 weeks of full 12-week treatment and frequent HCV PCR monitoring till achieving SVR
post-transplant to avoid severe acute HCV infection and also monitor for drug-drug interaction in particular CNI and m TOR inhibitors with DAA therapy due to shared cytochrome P450 metabolism.
DAA course for 1 month costs> 9000 $, its not in our formulary medication in our center, and requesting this treatment through the GI team only.
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. Reddy YNV, Reddy KP, Sise ME. HCV-Infected Deceased Donor Kidney Transplantation-Time to Take Up the Offer. Am J Kidney Dis. 2020 Jun;75(6):827-829.
2- 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 3- we can use basiliximab as induction 4- maintained on tacrolimus, MMF, prednisolone
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
Yes, I would accept the organ, but a series of precautions are extremely necessary.
1. Knowledge of the potential recipient of the serological status and active disease of the potential donor;
2. Knowledge of the diagnosis and whether there was previous treatment with direct-acting antiviral drugs (DAAA);
– If there was previous treatment and maintenance of the viral load or reinfection by the virus, I would not proceed with the transplant
3. Measurement of viral load;
4. Due to the high risk of disease transmission and the need for induction with rATG (deceased donor) with a triple regimen, I would proceed with Sofosbuvir + Velpastavir (pangenotypic regimen) on D0 of the transplant
5. Serum monitoring of immunosuppressants for possible drug interactions. Avoid sirolimus because it presents an intermediate interaction and measures calcineurin inhibitors.
Yes,
Test recipient for HCV.
Start DAA immediately post transplant. For 12weeks.
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.
.. Will you accept this allograft?
Yes.
.. If yes how you will proceed?
Yes, I will council the family,
will start DAA as soon as possible,
Will prefer induction with basiliximab,
Maintenance immunosuppression with as usual with triple regime.
Will follow the LFTs, HCV PCR surveillance at 3, 7, 10, 14 days and after 6 weeks.
Reference;
.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9053510/.
. Will you accept this DBD donor?
this donor is deceased donor with positive HCV Ab and HVC RNA which indicate active viral infection.
In case of organ donation, the risk of transmission is high but still it is not contraindicated due to the advent of DAAS leading to >95% cure rates and the ease of treating HCV posttransplant but still we have to counsel the patient about the risk of infection.
A recent report demonstrated high cure rates even in the liver transplant setting, suggesting that immunosuppression does not impede eradication and that the interactions between HCV and transplant drugs can be successfully managed
2. If yes, how would you proceed?
-Testing recipient for HCV AB and RNA, ALT , AST, AFP.
-If HCV-negative: he should receive DAA (SOF-based) therapy for 12 weeks
separate open-label trial demonstrated 100% SVR12 with 12 weeks of elbasvir/grazoprevir (± sofosbuvir) therapy initiated immediately prior to transplantation in 10 HCV-uninfected kidney transplant recipients of allografts from HCV-viremic donors
-If the Recipient is HCV-RNA positive :
this condition is associated with higher risk of viral replication, acute hepatitis, chronic hepatitis and cirrhosis, also extrahepatic manifestations of HCV as GN is an important risk.
-Liver function , AFP , fibroscan , liver biopsy should be done
If Compensated liver so,kidney transplant can be done with initiation of DAA treatment immediately before transplant.
-According to KIDIGO guidelines:
– viral RNA every 3-6months, AFP and liver USG every 6months for life
-If decompensated liver disease– combined liver + kidney transplantation.
With follow up for life also .
– it is important to investigate foe presence of HCC before TX or de novo post TX
-it is recommended that the candidates is considered for DAA therapy, either before or after transplantation.
-kidney transplant recipients being treated with DAAs be evaluated for the need for dose adjustments of concomitant immunosuppressants .
-patients previously infected with HCV who achieved SVR before transplantation undergo testing by NAT 3 months after transplantation or if liver dysfunction occurs .
-HCV-infected kidney transplant recipients should be tested at least every 6 months for proteinuria (Not Graded).
Reference
HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C | © 2014-2022 AASLD and IDSA v2022.1.
KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease
Yes, i would accept this DBD donor
Perform HCV PCR on post transplant 3-7day, 10-14day and 6 week, if negative then no transmission of HCV and reassure the patient. If positive then start DAA within 3-10working day for 3 month. Then SVR tested after 3 month of completion of DAA. if futher positive then another 3 month of DAA of other combination.
HCV antibody and HCV PCR are positive
Will you accept this DBD donor?
Yes
If yes, how would you proceed?
Reference
Q1: Yes, the donor has an active HCV infection, but according to the KDIGO guideline, if the donor has no HCV-associated nephritis (HCVAN), this kidney is considered for transplantation without considering HCV status, but DAA therapy should be considered.
Q2: DAA treatment should be initiated very soon if HCV PCR of the patient become positive and patient should be informed about the importance of situation and DAA treatment and follow-up.
Induction therapy with basiliximab is preferred. Maintenance immunosuppressive therapy with triple- therapy and HCV PCR monitoring at 3, 7, 10, 14 days and six-weeks later is recommended.
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 given recipient is offered a kidney from a 56 year old DBD…There is normal renal function…Cause of Brain stem death is subarachnoid hemorrhage….There is no evidence of Hep B or HIV…..There is evidence of Anti HCV and HCV RNA is also detected in the donor….There is underlying active HCV infection in the donor
HCV status of the recipient has not been provided…..As per the KDIGO guidelines, I will accept the donor irrespective of the recipient HCV RNA status…The donor has active HCV Infection with viremia…There is a high chance of transmission to the recipient as per the available literature….
The recipient has to be counselled about the above scenario and the need to start DAA immediately post transplant and monitor the HCV viral load….I would emphasize the monitoring of the HCV Viral load regularly….We should test HCV RNA quantitative on Day 3, day 7, day 14 and 6 weeks later…
As the recipient would be waiting on the deceased donor list, it is always better to have a renal transplant earlier rather than waiting for a HCV negative donor…With the advent of DAA, there is very less chance of progression of HCV in the recipient into chronic infection and cirrhosis….
If the scenario is a live donor with HCV positive:
In this case the donor health becomes a prority…The donor should be evaluated for features of LFT, RFT, urine routine, CBC, PT INR, USG whole abdomen, Fibroscan to rule of CLD..The donor should get done HCV RNA qauntitative done and treated before Transplant…It is best to treat HCV in the donor and then plan for elective surgery as surgery with High HCV has chances of activation of HCV into fulminant hepatitis….
Yes, today direct-acting antiviral (DAA) therapy also shows excellent results as a preventive therapy for the development of HCV infection.
– 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
– Treatment for a period of 12 weeks with antiviral therapy
1. Will you accept this DBD donor?
HCV Ab + and HVC RNA + indicates active viral infection (hepatitis) with high risk of transmission.
but with the availability DAA, which is effective both pre- and post- transplant, this donor can be accepted, if the recipient accepts after understanding the risks.
2. If yes, how would you proceed?
A. If Recipient HCV-negative:
We can accept the donor, with DAA (SOF-based) therapy for 12 weeks, starting -12hr /0-hr of transplant.
Recipient has to accept the risk of viral replication, hepatitis, associated complications; need for antivirals and side effects and life-long surveillance; including graft rejection and higher mortality.
B. Recipient is HCV+:
Donor HCV+ and Recipient HCV+ is associated with highest risk of viral replication, chronic hepatitis, cirrhosis and HCC; with Higher rate of all complications, graft-loss and mortality.
Recipient liver disease and condition should be thoroughly evaluated.
If Compensated liver disease à can proceed with kidney transplant, with DAA started peri-transplant; close monitoring of viral load, LFT, RFT, Tac C0 level and proteinuria.
– Needs life-long follow-up: viral RNA every 3-6months, AFP and liver USG every 6months
If decompensated cirrhosis – combined liver + kidney transplantation advised.
Peri-op care, antivirals and follow up remain more stringent.
KDIGO 2022 CLINICAL PRACTICE GUIDELINE For the Prevention, Diagnosis, Evaluation and Treatment of Hepatitis C in CKD recommends –
· Kidney transplantation is the best therapeutic option for patients with CKD G5 irrespective of presence of HCV infection.
·
It is recommended that kidneys from HCV-infected donors be considered regardless of HCV status of potential kidney transplant recipients
· The candidate with HCV should be evaluated for severity of liver disease and presence of portal hypertension prior to acceptance for kidney transplantation
· HCV patient with compensated cirrhosis, and no portal hypertension can go for isolated kidney transplantation.
· Patients with decompensated cirrhosis or clinically significant portal hypertension need a simultaneous liver–kidney transplantation.
· It is recommended that the candidates is considered for DAA therapy, either before or after transplantation.
· Post kidney transplant, recipients on DAAs needs evaluation for the need for dose adjustments of concomitant immunosuppressants.
1- This is an active viral hepatitis with high risk of transmission
but with the introduction of the DAA, this donor can be accepted
after explanation of the risks to the donor.
2- If the recipient is seropositive:
It is associated with higher all-cause mortality and higher all-cause graft loss.
and the recipient should be evaluated carefully regarding the liver function and
condition:
– If compensated, proceed and peri-transplant DAA should be started with close
follow-up
– If decompensated: combined liver and renal transplantatation
and accept the risk
we can accept with peri-transplantation SOF-based therapy for 12 weeks
· kidney transplantation is the best therapeutic option for patients with CKD G5 irrespective of presence of HCV infection.
· It is recommended that kidneys from HCV-infected donors be considered regardless of HCV status of potential kidney transplant recipients
· The candidate with HCV should be evaluated for severity of liver disease and presence of portal hypertension prior to acceptance for kidney transplantation
· HCV patient with compensated cirrhosis, and no portal hypertension can go for isolated kidney transplantation.
· patients with decompensated cirrhosis or clinically significant portal hypertension need a simultaneous liver–kidney transplantation.
· It is recommended that the candidates is considered for DAA therapy, either before or after transplantation.
· Post kidney transplant, recipients on DAAs needs evaluation for the need for dose adjustments of concomitant immunosuppressants.
KDIGO 2022 CLINICAL PRACTICE GUIDELINE FOR THE PREVENTION, DIAGNOSIS, EVALUATION, AND TREATMENT OF HEPATITIS C IN CHRONIC KIDNEY DISEASE
Yes I would accept this donor even though the risk of HCV transmission is high, but the donor can be started on DAA post-transplant, and it will reduce waiting time on HD.
Prior to transplantation the recipient must be counselled regarding the risk of HCV transmission, complication of HCV infection, duration of DAA and side effects of DAA. DAA can be started before, or after transplantation depending on transplant center protocols. Start DAA (Glecaprevir/Pibrentasvir) pre-operatively then daily for 7 days. Follow up PCR of recipient should be done at 3-7 days, then day 14 and then at 6 weeks. If HCV PCR is negative then no need for DAA, If PCR positive then DAA should be started within 10 days of positive PCR, and continued for at least 12 weeks, then PCR should be repeated to confirm SVR. As far as induction immunosuppression is concerned, ATG and Almetuzumab should be avoided. Induction with Basiliximab is preferred.
DONOR WITH HCV positive for ANTIBODY AND PCR cab be accepted for HCV PCR positive recipient with more all cause mortality
for HCV PCR negative recipient
this is HISH RISK transplant
can be accepted after counselling and weighted benefit of transplant and risk of nor getting organ
Post op HCV PCR to be done at 2 week , 1 month and 3 month
SOF based DAA should be started immediately
Will you accept this DBD donor?
Yes I will accept this DBD donor
HCV infection in the donor does not amount to an absolute contraindication to donation of material for life-preserving transplantation, however the net benefit of transplantation must be considered against the risk of not receiving that specific transplant. This risk/benefit analysis allows for the potential use of a transplant from a HCV infected donor to a non-infected recipient.
If yes, how would you proceed?
Patient Consent
If the recipient is HCV PCR -ve >>> should be tested for HCV PCR day 3-7 post transplant if the result was negative so the test should be repeated on 10 – 14 days post transplant if also negative repeat the test after 6 weeks after that if negative reassurance of the recipient about low risk of HCV transmission.
If positive result at any time of previous testing time >>> confirmatory test should be done and to starting DAA at 3 to 10 working days of the first positive result .
Yes, donor can be accepted. HCV Ab positive denotes previous infection& PCR is negative.
How to process:
-Recipient counselling regarding the risk of HCV infection.
-Commencement of DAA peri-operatively.
-Monitoring of viral load following transplantation.
According to the KIDIGO guied line will accept this donor to the HCV positive recepient other wise recently emerge data stat that we can proceed with this RTX from HCV + donor to recepient – along with full councelling to the reciepeint and start him on DAA immediately post RTX .
use of HCV RNA-positive donors is no longer a major concern with the advent of DAA therapy
– an HCV RNA-positive donor can donate to an HCV RNA-positive recipient as well as to an HCV RNA-negative recipient as long as this is followed by antiviral treatment
– excellent HCV cure rates and excellent short-term graft function and safety profile have been reported
– DAA therapy should be offered in the peri-transplant period to reduce the risk of chronic HCV infection in the transplant recipient
references
uptodate
1- This is an active viral hepatitis with high risk of transmission
but with the introduction of the DAA, this donor can be accepted
after explanation of the risks to the donor.
2- If the recipient is seropositive:
It is associated with higher all-cause mortality and higher all-cause graft loss.
and the recipient should be evaluated carefully regarding the liver function and
condition:
– If compensated, proceed and peri-transplant DAA should be started with close
follow-up
– If decompensated: combined liver and renal transplantatation
and accept the risk
we can accept with peri-transplantation SOF-based therapy for 12 weeks
Will you accept this DBD donor?
Case scenario
DBD
HCV positive
HCV PCR positive
After the advent of DAA such donors should be accepted
If yes, how would you proceed?
DAA should be started in post transplant period as per protocol.
The 2018 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend that kidneys from HCV-seropositive and RNA-positive donors should only be given to HCV RNA-positive recipients. However, emerging data demonstrating the safety of transplanting kidneys from HCV RNA-positive donors into HCV RNA-negative recipients with early or pre-emptive DAA therapy support the use of kidneys from high-risk deceased donors in uninfected patients when medical need is urgent and the benefits appear to outweigh the risks. In all such cases, the recipient should receive specific counseling, be well informed, and participate in decision making.up to date
Will you accept this DBD donor?
Yes.
Now HC+R used for HB_R AND HC +R routine clinical practice.1
DAA therapy (Panp-genotypic DAA) in the post-transplantation 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.
Follow up post-transplant ,monthly and genotype and presence of resistance-associated
substitutions (RAS).
References:
1-Terrault, Norah et al .International Liver Transplantation Society Consensus Statement
on Hepatitis C Management in Liver Transplant Recipients. Transplantation 101(5):p 956-
967, May 2017.
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 65 µmol/L. Virology was reported as follows: HBsAg negative, HBsAb negative, HBcAb negative, and both HBeAg and HBeAb are negative. HCV antibody and HCV PCR are positive. HIV is negative
Will you accept this DBD donor?
If yes, how will you proceed?
REF;
Morgan TR et al; Hep C guidance 2019,update;AASLD-IDSA recommendations for testing, managing and TX of HEP C infection. Hepatology 2020;71;686-721
Thanks
Thanks Prof.
2. 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 65 µmol/L. Virology was reported as follows: HBsAg negative, HBsAb negative, HBcAb negative, and both HBeAg and HBeAb are negative. HCV antibody and HCV PCR are positive. HIV is negative
Issues/ concerns
– 56yo male, DBD, suffered Grade 5 SAH complicating cerebral aneurysm
– retrieval sCr 65
– virology screen: HBsAg negative, HBsAb negative, HBcAb negative, HBeAg negative, HBeAb negative, HCV Ab positive, HCV PCR positive, HIV Ab negative
Will you accept this DBD donor?
– yes, I would accept this donor
– the demand for organs surpasses the supply resulting in long waiting times and significant waitlist mortality
– with the advent of DAA therapy, HCV-positive organs can now be used in both HCV-positive and HCV-negative recipients with favourable outcomes
If yes, how would you proceed?
– multidisciplinary approach – hepatologist, infectious disease specialist
– HCV Ab positive, HCV PCR positive indicates active HCV infection with a high risk of transmission
– HCV seropositivity is associated with higher all-cause graft loss and all-cause mortality
– use of HCV RNA-positive donors is no longer a major concern with the advent of DAA therapy
– an HCV RNA-positive donor can donate to an HCV RNA-positive recipient as well as to an HCV RNA-negative recipient as long as this is followed by antiviral treatment
– excellent HCV cure rates and excellent short-term graft function and safety profile have been reported
– DAA therapy should be offered in the peri-transplant period to reduce the risk of chronic HCV infection in the transplant recipient
– this potential kidney transplant recipient should be evaluated for a couple of things: –
– detectable HCV RNA indicates HCV infection;
– HCV infection prior to transplantation is not a contraindication to kidney transplantation
– but if not successfully treated, it increases post-transplant morbidity and mortality
– assess the extent of fibrosis using blood tests (e.g., APRI score – Aspartate aminotransferase (AST)-to-platelet ratio index (APRI)) and imaging tests e.g., performing transient elastography (1)
– liver biopsy was previously considered the gold standard however, nowadays it is only performed when noninvasive test results are discordant or when liver comorbidities are suspected
– these staging tests inform on the liver-related prognosis and help guide the selection of HCV treatment regimen as well as help decide on the type of transplant to be done i.e., kidney vs combined kidney-liver transplantation
– assess for portal hypertension if there is evidence of cirrhosis
– combined liver-kidney transplantation is offered to patients with decompensated liver disease, rapidly progressive liver disease, extrahepatic complications, compensated liver disease with portal hypertension
– kidney transplantation alone can be considered in patients with compensated liver disease without portal hypertension
– both pre- and post- transplant antiviral DAA therapy are highly effective and safe
– there are DAAs which are pangenotypic, with established safety and efficacy in severe kidney dysfunction (eGFR <30) and even in dialysis
– decisions on the timing of antiviral therapy (i.e., pre- vs post- transplant) depends on severity of liver disease, anticipated wait time on the transplant waiting list, accessibility of organs from HCV-positive donors, extrahepatic complications of HCV infection
– pre-transplant therapy is offered to patients with advanced or rapidly progressive liver fibrosis (but not decompensated cirrhosis) or severe extrahepatic manifestations e.g., cryoglobulinemic vasculitis
– patients with decompensated cirrhosis require a liver-kidney transplant, the decision on pre- vs post- transplant DAA therapy, is individualized depending on the MELD score, access to transplantation, available treatment options, the likelihood of meaningful response to therapy and expected virologic response
– patients without decompensated cirrhosis, advanced or rapidly progressive liver fibrosis or severe extrahepatic manifestations, the treatment options depend on whether they are using a deceased donor or a living donor
– for those on the deceased-donor waiting list, the decision is informed by the anticipated waiting time – if long then pre-transplant antiviral therapy is offered
– for those using living donors, pre-transplant therapy is offered unless there are limiting factors e.g., drug-drug interactions, inability to delay the transplant for 8-12weeks to allow for DAA therapy
– timing of DAA therapy (i.e., pre- vs post- transplant) primarily depends on the waiting list advantage and the impact of delay on HCV-associated mortality especially among patients with advanced fibrosis or 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
– in kidney transplant recipients, consider the presence and extent of kidney dysfunction and the potential interactions with immunosuppressive agents
– sofosbuvir-velpatasvir is pangenotypic
– in addition to the standard post-transplant care, 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 is an indication for 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
References
1. 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.
2. Parsikia A, Campos S, Khanmoradi K, Pang J, Balasubramanian M, Zaki R, et al. Equal 3-Year Outcomes for Kidney Transplantation Alone in HCV-Positive Patients With Cirrhosis. International surgery. 2015 Jan;100(1):142-54. PubMed PMID: 25594655. Pubmed Central PMCID: PMC4301280. Epub 2015/01/17. eng.
3. Bhamidimarri KR, Ladino M, Pedraza F, Guerra G, Mattiazzi A, Chen L, et al. Transplantation of kidneys from hepatitis C-positive donors into hepatitis C virus-infected recipients followed by early initiation of direct acting antiviral therapy: a single-center retrospective study. Transplant international : official journal of the European Society for Organ Transplantation. 2017 Sep;30(9):865-73. PubMed PMID: 28332729. Epub 2017/03/24. 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
Thanks
Will you accept this DBD donor?
DBD donor with HCV antibody and PCR positive.
Yes I would accept this donor since HCV infection is not an absolute contraindication for donation.
If yes, how would you proceed?
The recipient needs to be counselled on the risk of HCV transmission and consent obtained.
The recipient HCV antibody and PCR status should be known and if positive the recipient should not have liver cirrhosis.
The recipient should have high likely hood of achieving SVR12.
The donor HCV genotyping should be done.
Post-transplant recipient could have HCV PCR done frequently starting immediate post transplant period.
Any 2 positive PCR warrants prompt initiation of DAA that are pan-genotypic after transplantation and have minimal drug interaction.
The DAA ideally should be given for 12 weeks but may be given for up to a period of 6 months.
References
UK Position Statement on the use of Organs from Hepatitis C Viraemic Donors and Increased Infectious Risk Donors in Hepatitis C Negative Recipients
Thanks
Yes I will accept this DBD
This is HCV positive donation to HCV -/+ recipient , I will proceed to transplantation with DAA therapy to be administered at the time of transplant or early thereafter for 4–8 weeks is safe and effective to prevent complications of HCV infection in the recipient with excellent rates of viral clearance (SVR12) as well as excellent allograft function and survival, with excellent patient survival rates at 1 year following transplant .
Induction of immunosuppression is preferred with basiliximab over lymphocyte depleting agents ,maintenance with tacrolimus,MMF,prednisolone with drug level monitoring and follow up of viral PCR at (3,7,14 days, and 6 weeks)
.
Refrence :
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
Thanks
yes, I will accept if there is a need for urgent transplantation (pt with vascular access failure or expected a long waiting list
) Or no available non-HCV donor.
-If the recipient is also HCV positive, I will assess the liver status; if the AST/platelet ratio is 0.8, I will refer to a hepatologist first to be included in MDT, and I will start DAA medications before surgery and continue post-transplant.
-if the recipient is HCV negative, I will proceed with the high risk of viral transmission with the benefit of transplant over dialysis or being on a waiting list for long time, with prophylactic initiation of DAA follow-up the LFTs, HCV PR, monitor drug-drug interactions
-the donor is better being of low or moderately high immunological risk for induction with basiliximab.
>>Reference: UK-Position-Statement-on-the-use-of-Organs-from-Hepatitis-C-Viraemic-Donors-in-Hepatitis-C-Negative-Recipients-Final-Version-BASL-Website
Thanks
Will you accept this DBD donor?
Yeas I will accept . this patient had HBsAg negative, HBsAb negative, HBcAb negative, and both HBeAg and HBeAb are negative. But he positive for HCV antibody and positive for HCV PCR. HIV is negative. Evidence shows that HCV transmission from HCV antibody positive NAT negative donor to HCV naive recipient is low.
If yes, how would you proceed
Firstly council the recipient about risk of HCV infection .
For the rapidly evolving treatments for HCV have improved outcomes, and perioperative use of DAA therapy has increased the utilization of HCV- viremic donor organs.
hepatitis C treatment have led to a success rate of over 95%.
We need to check PCR for HCV in 1st,2nd week after transplantation ,6 week and 3 month ,If HCV PCR is positive, we need to start DAA within 3-10 days of positive HCV PCR and continue for 12 weeks. Then we have to follow up HCV PCR to confirm SVR, Induction therapy with basiliximab, unless patient is highly sensitized.
DAA may be necessary for up to 6 months post-transplant.
References
1.Updated October 2021. Accessed November 7, 2021. 4. Global Observatory on Donation and Transplantation. International report on organ donation and transplantation activities. Executive summary 2019. http://
2. – 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
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 only if the recipient is in urgent need for a graft (those with no vascular access or those with expected very long time on waiting list) 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 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
References
1- Utilization of HCV viremic donors in kidney transplantation: a chance or a threat?
Will you accept this DBD donor?
The donor is negative for HBsAg, HBsAb, HBcAb, HBeAg and HBeAb but is positive for HCV Ab and HCV RNA by PCR. Yes, this DBD donor may be accepted for transplantation.
The latest developments in hepatitis C treatment have led to a success rate of over 95%. Most of who have been infected can now be treated using directly acting antiviral agents. It has been found that results are favorable for recipients who do not have Hepatitis C, who have received organs with hepatitis C and they were later treated and cured of the virus. Suitable donors are declined often because of the risk of transmission of hepatitis C. Using organs from such donors could be life saving.
Previously kidneys from HCV-infected donors were almost exclusively transplanted into HCV-infected patients, but with the introduction of DAA therapy, kidneys from HCV-infected organs are increasingly being transplanted into HCV-negative patients.
If yes, how would you proceed?
We have to start DAA therapy as early as possible, prior to transplant surgery. Induction agent would preferably be an agent that would not result in a pronounced replication flare of the virus. Induction would be with Basiliximab since ATG has been found to worsen the infection. Patient should receive tacrolimus, steroid and MMF. The interaction between the different DAAs and post-transplant immunosuppression medications have to be considered.
The recipient must be adequately counseled and provided with sufficient information for an informed consent. Need for dose adjustments of concomitant immunosuppressants post-transplant have to be considered by drug monitoring.
Patients must undergo testing for HCV RNA by PCR at 1st week, 2nd week, 6th week and 3 months after transplantation or if liver dysfunction occurs. If HCV PCR is negative on two subsequent testing, DAA is not needed. If HCV PCR is positive at any time, we need to start DAA within 3-10 days of positive HCV PCR and continue for 12 weeks. Then we have to follow up HCV PCR to confirm SVR. DAA may be necessary for upto 6 months post-transplant.
References:
Ghany MG, Morgan TR. Hepatitis C Guidance 2019 Update: American Association for the Study of Liver Diseases-Infectious Diseases Society of America Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection. Hepatology 2020; 71: 686-721.
UK position on the use of organ from HCV donors and increased infectious risk donors in Hepatitis negative recipients. UK Position Statement on the use of Organs from Hepatitis C Viraemic Donors and Increased Infectious Risk Donors in Hepatitis C Negative Recipients – British Transplantation Society (bts.org.uk)
Excellent
Thanks
For this scenario, I will accept the donation after insurance of the availability of direct anti-viral therapy and start preoperatively. We should realize that strict trials like THINKER and EXPANDER-1, although encouraging results in other trials reflecting the real world, showed an increased risk of transaminitis and higher polyomavirus infection. Attaining sustained viral response is important. Starting preoperatively will be safer and decrease the risks.
——-
√ 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.
How would you proceed?
Reference:
· UpToDate
Short and sweet.
Yes i can procced for donation
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. 4. Global Observatory on Donation and Transplantation. International report on organ donation and transplantation activities. Executive summary 2019. http:// http://www.transplant-observatory.org/wp-content/uploads/2021/06/GODT2019- data_web_updated-June-2021.pdf. Published April 2021. Accessed August 6,
Short and sweet.
Will you accept this DBD donor?Yes, I will accept this kidney donation offer if there is availability of HCV treatment post renal transplantation because:Donor is DBD. Donor’s HBV, and HIV are negative. Negative FCXM.Donor has positive HCV Ab and HCV PCR.There is high risk of HCV transmission from positive donor to negative recipient. However, transplanting kidneys from HCV positive donors to recipients with negative HCV will reduce the waiting time on dialysis and enlarge the donation pool.
If yes, how would you proceed?
1- The recipient must be counselled before transplantation about the protentional risk of HCV infection from infected donor.
2- DAA can be started either before transplantation or after transplantation depending on centers protocols.
3- Start DAA (Glecaprevir/Pibrentasvir) pre-operatively then daily for 7 days.
4- Recipient follow up of HCV PCR: at 3-7 days then at day 14 then at 6 weeks.
If HCV PCR is negative, DAA is not needed
If HCV PCR is positive at any time, start DAA within 3-10 days of positive HCV PCR and continue for 12 weeks. Then follow HCV PCR to confirm SVR.
5- Induction immunosuppression: Basiliximab (IL2R) , try to avoid ATG or Almetuzumab.
6- Follow up with infectious disease and hepatology team to monitor for liver cirrhosis, liver cell failure, portal hypertension.
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, well done.
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.
If yes, how would you proceed?
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.
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.
What is the induction agent you would use?
Will you accept this DBD donor?
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.
If yes, how would you proceed?
1. I would proceed if the followings are met:
a. Donors do not have cirrhosis.
b. 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).
2. In such situation, I will initiate DAAs in the early post-transplant period.
3. HCV PCR to be checked in the post-transplant period at day3-day7 – day10 -day14 and 6weeks post-transplant.
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.
What is the induction agent you would use?
The donor with HCV viremia can be accepted to reduce the risk of long waiting time. However, we need to start antiviral treatment immediately to prevent viral transmission as it was shown that it is almost 100% without treatment.
However, given the significant survival benefit from transplant, HCV-viremic to HCV-naive transplant with concomitant DAA therapy can improve outcomes for patients with ESRD because transmission can be prevented by prophylactic DAA therapy and there is a high cure rate for post-transplant patients with established infection. A multicenter open-label trial of 30 patients who received glecaprevir-pibrentasvir therapy started within 3 days of HCV viremic kidney transplant and continued for 8 weeks. All patients achieved SVR and no severe adverse events were deemed related to HCV infection or glecaprevir-pibrentasvir
therapy. Taken together, these data demonstrate that the best patient outcomes are obtained with prophylactic DAA or DAA therapy initiated shortly after transplant.
Counselling the recipients about risk and benefit and treatment plan.
Will give glecaprevir-pibrentasvir therapy started within 3 days of HCV viremic kidney transplant and continued for 8 weeks.
Induction therapy with basiliximab, unless patient is highly sensitized.
Close monitoring of his liver function, coagulation profile, HCV PCR.
Involvement of hepatologist and clinical pharmacist. Close monitoring of kidney function, tacrolimus level for the potential of drug interaction.
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, well done
Will you accept this DBD donor?
Yes I will accept this donor.
If yes, how would you proceed?
But there is an important caveat that what is the dire emergency of accepting an infecting organ.
REF:
What is the induction agent you would use?
Do not forget, the availability of DAA makes it easier to transplant HCV positive to negative.
Donor Virology and acceptance
HBsAg negative, HBsAb negative, HBcAb negative, both HBeAg and HBeAb are negative. HCV antibody and HCV positive. HIV negative.
The donor is HCV positive with HCV antibodies. I would accept this donor if there is no other suitable donor available in the immediate future. The lifespan and quality of life of the recipient only worsens day by day on the waitlist while receiving regular dialysis.
Evidence shows that HCV transmission from HCV antibody positive NAT negative donor to HCV naive recipient is low. However, our donor does not come under this category.
The combination of donor’s antibody and NAT status provides an understanding of the chronicity and transmissibility of their infection. NAT provides an accurate assessment of HCV risk of transmission from transplantation.
HCV antibody positive NAT positive donors pose a higher risk of disease transmission to the recipient. The recipient will most probably become viremic after transplant and will need anti viral therapy. However, in 12 weeks, it is possible to find that our recipient is virus free with undetectable HCV RNA levels. The patient also has a high chance of good graft function with less risk of graft loss or mortality of the patient.
I would accept this donor provided the recipient has given full informed consent.
Proceeding with transplant
The important aspect to consider for good outcome is to give sufficient antiviral prophylaxis post transplant to the recipient. DAA will be administered to the recipient immediately post transplant with close monitoring of drug levels of IS regimen. Induction would be with Basiliximab since ATG has been found to worsen infection. Patient will receive triple IS regimen – tacrolimus, steroid and MMF. Monitoring of drug levels is essential since DAA can cause fluctuations in IS drug levels leading to either insufficient immunosuppression, thereby increasing risk of graft rejection, or too much immunosuppression, increasing risk of infection and toxicity of IS drugs.
References
⭐ ⭐ ⭐ Accepting HCV postive donor for HCV naive recipient could be accepted in case of long waiting time on dialysis (transplantation from HCV viremic organs has better survival than dialysis).
⭐ but only after counseling, obtaining consent, starting preemptive antiviral in the day before transplantation and for 3 months until achieving SVR with EBR_GZR.
What is the induction agent you would use?
_ no available data about immunological risk , cross match and HLA mismatch or blood group.
But, I will use induction with basiliximab if no immunological risk to prevent flaring up of viremia.
-Yes ,as DAAT availability improves the outcome with high rate of HCV cure
– MDT have to be involved including a virologist and hepatologist
The recipient either HCV positive or negative has to be informed about the donor status and sign the HCV specific consent.
This donor has HCV RNA positive and HCV Ab positive denoting HCV viremia with risk of HCV infection transmission therefore pangenotypic agents for long or intermediate post-transplant durations can lead to favourable outcomes
The recipient have to be monitored for HCV viraemia at postoperative day3receive DAAT immediately post transplant for 12 weeks with following SVR 12 ,immunosuppression given have to be closely monitored to avoid drug -drug interaction .
Gupta et al used a trial design using 2-4 doses of pangenotypic SOF and Velpatasvir (VEL) on transplant day 0–4, immediately started pre-transplant to prevent transmission in 50 recipients. 6 cases across all phases of the study required 3 months of DAA treatment for HCV transmission. This regimen was associated with a lower SVR12 compared to other trials (98%).
Current induction and maintenance immunosuppressives can be used in HCV-infected kidney transplant recipients
Reference
-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.
– Chow K. M. KDIGO GUIDELINES TREATMENT OFHCVINKIDNEY TRANSPLANT RECIPIENTS
What is the induction agent you would use?
Interleukin 2 receptor antagonist basilixamb
Will you accept this DBD donor?
In this case the donor is HCV antibody and HCV PCR are positive.
Yes I will accept him for kidney donation as the outcomes are still superior to staying on long term dialysis.
If Recipient is HCV negative then detailed counselling is required. In such scenario, HCV PCR should be done at week1 , Week 2 and Week 6.
HVC PCR Negative- No action , only reassurance
HVC PCR Positive- Start DAA within one week of positive test till SVR is achieved .
If recipient is HCV positive , I will start DAA early after transplant.
If yes, how would you proceed?
Patient has to be counselled in detailed about the potential infected organ. I will counsel him about graft survival , outcomes and mortality . I will explain that transplantation in such situation is superior to dialysis or staying on waiting list.
DAA has to be started 3 days post transplant.
In such scenarios it will be sensible to avoid ATG
Triple immune suppression with TAC, MMF and Prednisolone.
Frequent monitoring of drug levels and adjusting the doses
I will be vigilant about drug interactions which may change drug levels and pose risk of rejection.
Also a monitoring is required for infections, malignancy an drisk of recurrence of primary disease.
Salvadori M, Tsalouchos A. Hepatitis C and renal transplantation in era of new antiviral agents. World J Transplant. 2018 Aug 9;8(4):84-96.
Jandovitz N, Nair V, Grodstein E, Molmenti E, Fahmy A, Abate M, Bhaskaran M, Teperman L. Hepatitis C-positive donor to negative recipient kidney transplantation: A real-world experience. Transpl Infect Dis. 2021 Jun;23(3):e13540.
KDIGO The 2022 Hepatitis C in CKD Guideline
What is the induction agent you would use?
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 as well as positive HCV RNA PCR.
The scenario implies an untreated or partially treated (if known HCV infection previously) HCV infection (1).
The HCV status of the recipient has not been provided. Nevertheless, I will accept this donor, after counselling the recipient, and if the prospective recipient agrees for post-transplant surveillance required in this scenario as well as there is availability of directly acting antivirals (DAAs), if needed (2). HCV positive donors can be accepted regardless of the HCV status of the potential kidney transplant recipient (1).
In case the recipient is HCV negative, then post-transplant, the recipient should be tested for HCV RNA PCR (2). The HCV RNA PCR 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 DAAs within 3-10 days (2).
In the scenario of a live donor who is anti-HCV antibody positive and HCV viremic, 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, Hepatitis B virus infection assessment, 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 (3).
Donor evaluation: The prospective donor who is positive for anti-HCV antibodies as well as HCV RNA PCR, 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. The DAA treatment of the donor can be delayed if the recipient requires transplant urgently due to reasons like poorly tolerating dialysis, or poor vascular access (1).
In the index scenario, as the live donor is HCV RNA PCR positive, it is preferable to treat with DAA prior to donation. 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 pre-transplant if the expected transplant will take place after more than 24 weeks (3). If there is urgency (poor vascular access, patient not tolerating dialysis), or if the transplant is expected in less than 24 weeks (12 weeks of therapy and 12 weeks of follow-up for SVR12), then the transplant can be proceeded with and the treatment of the recipient using DAAs can be done in the immediate pre-transplant or early post-transplant period (3).
References:
Thanks, well done.
The recipient should be counselled also.
Will you accept this DBD donor?
If yes, how would you proceed?
References:
KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease. Kidney Int. 2022.
Ronit Patnaik, MD, Eugenia Tsai. Hepatitis C Virus Treatment and Solid Organ
Thanks, well done.
Will you accept this DBD donor?
Yes, I will accept (although this is active HCV infection with high risk of transmission) provided that:
1. Patients have an access to DAA therapy
2. Comprehensive HCV monitoring
3. National/local regulations permit it
4. Specific comprehensive informed consent
5. Close follow-up to capture complications
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
Transplantation of HCV-viremic organs into HCV-naive recipients followed by the use of DAA agents provides excellent patient and allograft survival. Securing DAA therapy post-transplant is essential and patients should be fully informed of the associated risks, including the potential of HCV treatment failure
Risks of HCV D+ to R- transplantation:
1. fibrosing cholestatic hepatitis (FCH). It is an aggressive form of HCV recurrence seen in 1.5% in kidney transplant
2. infection transmission (DAA therapy results a high cure)
3. DAA treatment failure (<5%)
4. Extra-hepatic manifestations of HCV (cryoglobulinaemic vasculitis) or PTLD
5. Sexual transmission of HCV to a partner [(extremely low (<2% perhaps)]
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
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 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.
What is the induction agent you would use?
Than you prof.
Basiliximab induction therapy
This is a Hepatitis C viremic DBD donor who is hepatitis B negative
He has a normal creatinine and the cause of death SAH
I would accept this donor
The preferred recipient would be a hepatitis C positive recipient
If there would be no hepatitis C positive recipient, we can select a hepatitis C negative recipient after counseling and getting informed consent
We should involve a hepatologist who has experience in treating HCV
More history about the donor should be sought – especially if there was a history of previous treatment as that suggest resistant genotype of HCV
The HCV genotying should be done although results would take a few days and the donor center should communicate the results to the recipient center
The HCV negative recipient should have HCV RNA monitored after 3-7 days, then after 10 – 14 days then 6 weeks. If the HCV RNA turns positive, a second HCV PCR should be done. The patient should be treated with Direct Acting Antiviral Agents which are pangenotypic and it should be started within 3 – 10 days of the results of the first HCV PCR test.
The patient should be treated for 12 weeks and during that period the tacrolimus levels should be monitored
If after six weeks, the HCV RNA is remains negative, then there is no need for further testing
UK Position Statement on the use of Organs from Hepatitis C Viraemic Donors and Increased Infectious Risk Donors in Hepatitis C Negative Recipients
What is the induction agent you would use?
For this patient I would use Basiliximab as the induction agent
deceased donor with HCV with PCR positive is an increased risk of HCV infection in the recipient, also increasing morbidity and mortality.
counseling the recipient about the risk of infection, the medical needs outweigh the risk of infection, and sharing the patient in the decision.
2018 KIDIGO guidelines recommended that kidneys from HCV seropositive and RNA positive donors should only be given HCV RNA positive recipients, however, data demonstrate the safety of Transplant kidneys from HCV RNA positive donors to HCV negative recipients early or pre-emptive with DAA
do lad urine for haematuria or proteinuria and KFT
if the recipient after counseling,he accepts the transplant for HCV
for the deceased donor do KFT, urine for hematuria and proteinuria
pre-emptive DAA treatment and follow-up by PCR HCV,LFT,liver enzyme
references
uptodate
kidigo 2018
What is the induction agent you would use?
Our donor is HBsAg negative, HBsAb negative, HBcAb negative, and both HBeAg and HBeAb are negative.
HCV antibody and HCV PCR are positive. HIV is negative.
Will you accept this DBD donor?
Yes, I will accept.
My argument based on many points :
1- HCV-seropositive patients lived longer with transplantation (aHR at 3 years, 0.42; 95% CI, 0.27-0.63) compared to remaining on the waitlist.(1)
2- Treatment of HCV recipient with DAA with high curable rate before or after transplantation(2).
3- Studies shown great result in outcome, some shown no recipient became infected with chronic HCV with DAA treatment (3).
If yes, how would you proceed?
1-Recipients monitored for HCV viremia starting at postoperative day 3.
2- Once HCV RNA detected: elbasvir–grazoprevir (Zepatier) treatment for 12 weeks and following the response.
3-Basiliximab induction is favored over ATG for induction.
3-We should closely observe immunosuppression levels, to avoid drug-drug interactions.
References:
1-Sawinski D, Forde KA, Lo Re V 3rd, Goldberg DS, Cohen JB, Locke JE, Bloom RD, Brensinger C, Weldon J, Shults J, Reese PP. Mortality and kidney transplantation outcomes among hepatitis C virus-seropositive maintenance dialysis patients: a retrospective cohort study. Am J Kidney Dis 2019;73:815-826.
2-KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease. Kidney Int. 2022
3-Durand CM, Bowring MG, Brown DM, Chattergoon MA, Massaccesi G, Bair N, Wesson R, Reyad A, Naqvi FF, Ostrander D, Sugarman J, Segev DL, Sulkowski M, Desai NM. Direct-acting antiviral prophylaxis in kidney transplantation from hepatitis C virus–infected donors to noninfected recipients: an open-label nonrandomized trial. Ann Intern Med 2018;168:533-540.
Thanks Mohamed
Thanks,Why ATG induction?
Will you accept this DBD donor?
Donor kidneys with HCV infection are accepted for donation, regardless of the HCV status of the recipients. I shall therefore accept the patient.
As there is a high risk that the recipient of the kidneys from HCV Ab +/ HCV PCR+ donors would develop the hepatitis C virus, I will accept the patient’s kidneys provided DAA is available. When transplanting HCV-infected kidneys into HCV-uninfected recipients, transplant hospitals must instruct and notify their patients. Patients need to be aware of the advantages and disadvantages of HCV-infected kidney transplantation, including DAA therapy.
Transplant centers should check DAA availability for early post-transplantation when kidneys are donated by HCV positive to HCV negative.
If yes, how would you proceed?
With the purpose of lowering the risk of HCV-related liver damage, DAA should be begun as soon as possible after transplantation.
If available, the DAA regimen is chosen in accordance with the viral genotype. Whenever possible, adopt pan-genotypic therapy. Although the timing of antiviral medication is universal, it is advised to start it as soon as possible after transplant.
Basiliximab induction is favored over ATG for induction.
Tacrolimus, MMF, and prednisolone used as a maintenance immunosuppressive drug with regular trough level monitoring. HCV PCR testing should be done often along with drug administration (3,7,14 days, and 6 weeks).
Thanks, acknowledged
Yes, this donor can be accepted after counselling the recipient and ensuring the availability of DAA therapy as the cumulative risk of remaining on waiting list or dialytic support is worse when compared to undergoing renal transplantation.
Initiation of prophylactic therapy combining DAA with ezetimibe right before transplantation up to 7 days course can reduce the probability of viral infection.
Special emphasis would be on the type of DAA therapy that causes less interactions with immunosuppressive agents. The use of induction therapy must be cautious with offering better matching is considered the best.
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 assess hepatic tissue status ,decide the best choice of DAAs therapy until obtaining HCV PCR below detection level two or three times ,renal transplantation can be done safely afterwards.
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.
(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.
Thanks Samar
DAA treatment is highly successful, do not forget to exclude renal disease as well.
Looks a copy from your previous reply.
Thanks alot professor for highlighting this.
A 56-year-old male DBD donor had SAH (grade 5) complicating cerebral aneurysm, S Cr was 65 µmol/L,
HBsAg negative, HBsAb negative, HBcAb negative, HBeAg negative,
HIV negative.
HCV antibody and HCV PCR positive,
Will you accept this DBD donor?
Yes, I will accept this patient kidneys if there is availability of DAA as there is high risk of
transmitting hepatitis C virus infection in the recipient from HCV Ab +/ HCV PCR+
donors.
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
If yes, how would you proceed?
HCV Ab +ve Donor, HCV PCR +ve Donor TO HCV-ve Recipient:
Will 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.
HCV HCV Ab +ve Donor, HCV PCR +ve Donor TO HCV +ve Recipient:
MDT For GIT Evaluation of recipient to grade the fibrosis (fibro scan or liver biopsy),
portal hypertension.
Start DAA before or early after transplantation.
Safely Use Induction with Basiliximab(Simulect) :
IL2R as an induction agent avoid ATG/Alemtuzumab if possible.
References:
Lecture of Professor May Hassaballah in HCV and kidney transplant
KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease. Kidney Int. 2022.
Thanks Abdelhamid
DAA treatment is highly successful. Will you give treatment even if the PCR is negative (see your previous reply).
yes I will accept the donor but there is high risk of transmitting HCV infection
KDIGO guideline TREATMENT OF HCV IN KIDNEY TRANSPLANTRECIPIENTS
Position Statement on the use of Organs from Hepatitis C Viraemic Donors and Increased Infectious Risk Donors in Hepatitis C Negative Recipients (BTS)
Thanks Mohamed
DAA treatment is highly successful
if the patient on prolong waiting list and have no chance fr getting donor easily ….. yes i accept after counseling and starting anti HCV traetment for 3 months with close monitoring
Short and sweat Dalshad
Watch the spelling
Will you accept this DBD donor?
Yes, I will accept this patient kidneys if there is availability of DAA as there is high risk of transmitting hepatitis C virus infection in the recipient from anti HCV+/PCR+ donors.
If yes, how would you proceed?
HCV+ve D, HCV PCR+ve D/HCV-ve R
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.
HCV+ve D, HCV PCR+ve D/HCV+ve R
Need hepatologist evaluation of recipient for the grade of fibrosis (fibro scan or liver biopsy), portal hypertension.
Start DAA before or early after transplantation.
See drug interaction.
IL2R as an induction agent avoid ATG/alemtuzumab if possible.
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.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.
Thankyou.
Yes, the donor has been found to have positive levels of HCV antibody and HCR RNA.
This indicates that he has an active case of HCV infection.
A course of treatment to cure an R- patient who was to get a D+ organ would be less expensive than the cost of one year’s worth of dialysis
We urge that kidneys from HCV-infected donors be considered for transplantation independent of the HCV status of the prospective recipients of kidney transplants
To lessen the likelihood of developing a liver disease caused by HCV, DAA treatment should be started as soon as possible after transplantation. As a result, obtaining DAA treatment through contacts with insurance companies before moving forward with the transplant operation is an important component of the process.
Transplant centers are required to guarantee that patients get an education and are involved in conversations with adequate information to obtain informed consent before performing kidney transplants involving donors infected with HCV and recipients who are not infected with HCV.
Patients should be advised of the risks and advantages of receiving a transplant with an HCV-infected person, including the need for DAA therapy if they choose to proceed with the procedure.
Transplant hospitals should make sure that DAAs are available for early post-transplant treatment.
DAA chooses according to the genotype (if available). If not available, use pan-genotypic treatment.
Induction with basiliximab(as long as no indication for ATG)
continuous immunosuppressive medication (tacrolimus, MMF, and prednisolone), regular drug level and rejection monitoring, and HCV PCR (3,7,14 days, and 6 weeks).
References:
KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease. Kidney Int. 2022.
Ronit Patnaik, MD, Eugenia Tsai. Hepatitis C Virus Treatment and Solid Organ
Well done.
DBD donor with anti HCV Ab +/ HCV PCR +ve , negative HBV serology and Negative HIV.
Will you accept this DBD donor?
Yes, I will accept this patient kidneys, given the favorable outcomes, than being for long time on dialysis and transplant waiting list with a proposed 68% mortality reduction.
Whatever the HCV status of the recipient.
In HCV-ve 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.
In HCV+ve recipients I would start DAA therapy before or early after transplantation.
If yes, how would you proceed?
I will discuss the issue of having a HCV infected organs, with the recipient and the overall outcomes, graft survival and mortality, and how this practice is approved lastly by evidence and better than being on dialysis, or for long time on waiting list, and the availability of new drugs DAA with sustained viral response reaching 100%.
The options for the recipient are:
· Prophylactic initiation of antiviral therapy 12 hours before transplantation for 7 days (glecaprevir/pibrentasevir and ezetimibe).
· Initiation of DAA immediately after transplantation- EXPANDER-1 trial.
· Initiation of DAA with onset of viremia- 3 days after transplantation- THINKER tria.-elbasvir/grazoprevir
I will try to avoid the use of ATG and use of less drug-drug interaction maintenance immunosuppressive therapy( tacrolimus+MMF+prednisolone) with frequent monitoring of drug level and monitor for rejection, the long term risk of infection, malignancy, and recurrence of primary renal disease more seen in HCV infected recipients.
References:
(1) Roth D, Gaynor JJ, Reddy KR, Ciancio G, Sageshima J, Kupin W, Guerra G, Chen L, Burke GW 3rd. Effect of kidney transplantation on outcomes among patients with hepatitis C. J Am Soc Nephrol. 2011 Jun;22(6):1152-60. doi: 10.1681/ASN.2010060668. Epub 2011 May 5. PMID: 21546575; PMCID: PMC3103735.
(2) 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.
(3) Baid-Agrawal S, Pascual M, Moradpour D, Somasundaram R, Muche M. Hepatitis C virus infection and kidney transplantation in 2014: what’s new? Am J Transplant. 2014 Oct;14(10):2206-20. doi: 10.1111/ajt.12835. Epub 2014 Aug 4. PMID: 25091274.
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.
Well done your follow up regardless of the viral status is very well performed.
Given the option of receiving kidneys from a male DBD (donor after brain stem death) donor who was 56 years old and had a grade 5 SAH complicated a cerebral aneurysm.
His S Cr upon retrieval was 65 mol/L.
According to reports on virology:
HBeAg, HBeAb, and HBcAb are all negative, as well as HBsAg and HBsAb.
Both the HCV PCR and HCV antibody are positive.
HIV is absent.
Yes I will precede transplant with this donor
Excellent viral, allograft, and patient outcomes are linked to kidney transplantation from HCV-infected donors to uninfected recipients with prompt or early DAA treatment
HCV-infected kidney transplantation into HCV-uninfected patients is a cost-effective (and frequently cost-saving) approach that enhances clinical results.
Based on the evidence supporting the increased use of organs from HCV-infected DD-like IVDA donors with early use of DAA therapy that provides a high cure rate and well-tolerated course, we can still accept kidneys from HCV-infected donors to potential recipients
Further management
Informed consent and explaining for future risk and benefit for HCV positive donor
Obtaining an HCV-infected kidney depends on a number of variables, including the availability of DAA, the length of the wait, and the organ’s quality.
Throughout the first four weeks of the complete 12-week treatment period, early DAA medication is preferred before or right after transplantation, with frequent HCV PCR monitoring until reaching SVR.
And also need frequently monitoring of HCV infection post transplant for active infection and its complication.
Drug- drug interaction with DAA and immunosupression and also need to monitor their side effect
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.
HCV-Infected Deceased Donor Kidney Transplantation-Time to Take Up the Offer
Yuvaram N V Reddy 1 , Krishna P Reddy 2 , Meghan E Sise 3
Hepatitis C Virus Treatment and Solid Organ Transplantation #
Ronit Patnaik, and Eugenia Tsai,
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?
Conditions which should be met:
References
Thankyou but you went back to scenario1!!
Q2
Reference:
Well done.
Thnxs prof
2. 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 65 µmol/L. Virology was reported as follows: HBsAg negative, HBsAb negative, HBcAb negative, and both HBeAg and HBeAb are negative. HCV antibody and HCV PCR are positive. HIV is negative
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History
Will you accept this DBD donor?
Yes I will accept this donor .
If yes, how would you proceed?
====================================================================
Reference
Well done
Thanks alot for you Prof.Dawlat
I would accept the donor if transplantation is urgently indicated as in case of exhausted vascular access availability. In this case two approaches are advocated in Thinker and Expander II studies which are either to start DAA therapy right before transplantation and continue thereafter. or observe and follow up closely for infection transmission , then to commence DAA.
If there is no urgency in transplantation then proper treatment of the donor to achieve SVR for 6-12 months before proceeding with transplantation.
Reference:
1]Pagan et al. Should my patient accept a kidney from a hepatitis C virus-infected donor?.Kidney 360 1[2] :p127-129,Feb 2020
This is a DD! so your first action is the correct one.
yes dear prof
Will you accept this donor and how would you proceed?
The donor is both HCR RNA and HCV antibody positive.That means he has active HCV infection.”A course of therapy to cure a R- patient receiving a D+ organ would be less than the cost of dialysis for one year”KDIGO guidelines on HCV (2022) mention that –
“We recommend that kidneys from HCV-infected donors be considered regardless of 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 transplantation with an HCV infected kidney, including the need for DAA treatment (Not Graded).When transplanting kidneys from HCV-infected donors into HCV-uninfected recipients, transplant centers should confirm availability of DAAs for initiation in the early post-transplant period (Not Graded)BTS guidelines mention that :
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.UK Position Statement on the use of Organs from Hepatitis C Viraemic Donors and Increased Infectious Risk Donors in Hepatitis C Negative Recipients
Interpretation this Case according virology report:
HBsAg / HBsAb / HBcAb / HBeAg / HBeAb –—– (negative)
HCV Ab (positive) / HCV PCR (positive)
HIV (negative)
This patient is negative to (HBV& HIV) but this patient has (HCVAb&PCR positive)
My impression;
(Active HCV infection with high transmission risk).
1-Will you accept this DBD donor?
Yes; I will accept this DBD donor
-Prior to 2014, kidneys from HCV-infected donors were almost exclusively transplanted into HCV-infected patients.
-This was due to the limited treatment options, and the increased risk of death, graft loss, and severe liver disease compared with HCV recipients who received kidneys from HCV-negative donors.
-However, with the advent of DAA therapy, and the rapid increase in the number of deceased donors infected with HCV in some parts of the world due to the opioid epidemic, kidneys from HCV-infected organs are increasingly being transplanted into HCV-negative patients.
According KDIGO-2022 guidelines;
-Kidney transplantation Is the best therapeutic option for patients with CKD G5 irrespective of presence of HCV infection. (1A)
-Kidneys from HCV-infected donors be considered regardless of HCV status of potential kidney transplant recipients. (1C)
2-If yes, how would you proceed?
Keep in mind;
-Short term outcomes,
-Incidence of CMV and BK viremia higher than expected in HCV negative recipients,
-All HCV-negative patients received formal education about the risks and unknowns of being transplanted with a kidney from an HCV-infected donor, and this practice, along with a formal informed consent process, must be part of any protocol that involves transplanting kidneys from HCV-infected donors into HCV-negative patients.
-Because the only reported cases of fibrosing cholestatic HCV in the setting of transplanting kidneys from HCV-infected donors into HCV-negative recipients occurred with delayed initiation of therapy (two of the cases were >80 days post-transplant), it is recommended to start DAA therapy as early as possible,
-The interaction between the different DAAs and transplant immunosuppression,
-Management of HCV-related complications in kidney transplant recipients.
For proceeding HCV infected donor: I will follow KDIGO Guidelines;
– 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 transplantation with an HCV-infected kidney, including the need for DAA treatment. (Not Graded)
-When transplanting kidneys from HCV-infected donors into HCV uninfected recipients, transplant centers should confirm availability of DAAs for initiation in the early-post transplant period. (Not Graded)
-However, there are insufficient data to determine the exact time point at which DAA therapy should be started (e.g., 3 days vs 7 days vs 28 days).
-Kidney transplant recipients being treated with DAAs be evaluated for the need for dose adjustments of concomitant immunosuppressants. (1C)
-Patients previously infected with HCV who achieved SVR before transplantation undergo testing by NAT 3 months after transplantation or if liver dysfunction occurs. (2D)
-Kidney transplant recipients with cirrhosis should have the same liver disease follow-up as non-transplant patients, as outlined in the American Association for the Study of Liver Diseases (AASLD) guidelines. (Not Graded)
-HCV-infected kidney transplant recipients should be tested at least every 6 months for proteinuria. (Not Graded).
-Patients who develop new-onset proteinuria (either urine protein-creatinine ratio > 1 g/g or 24-hour urine protein > 1 g on 2 or more occasions) have an allograft biopsy with immunofluorescence and electron microscopy included in the analysis. (2D)
-Treatment with a DAA regimen in patients with post-transplant HCV-associated glomerulonephritis (1D).
References:
-Mandal AK, Kraus ES, Samaniego M, et al. Shorter waiting times for hepatitis C virus seropositive recipients of cadaveric renal allografts from hepatitis C virus seropositive donors. Clin Transplant 2000; 14: 391-396.
-Goldberg DS, Abt PL, Blumberg EA, et al. Trial of Transplantation of HCV-Infected Kidneys into Uninfected Recipients. N Engl J Med 2017; 376: 2394-2395.
-Durand CM, Bowring MG, Brown DM, et al. Direct-Acting Antiviral Prophylaxis in Kidney Transplantation From Hepatitis C Virus-Infected Donors to Noninfected Recipients: An Open-Label Nonrandomized Trial. Ann Intern Med 2018; 168: 533-540.
-Reese PP, Abt PL, Blumberg EA, et al. Twelve-Month Outcomes After Transplant of Hepatitis C-Infected Kidneys Into Uninfected Recipients: A Single-Group Trial. Ann Intern Med 2018; 169: 273-281.
-Molnar MZ, Nair S, Cseprekal O, et al. Transplantation of kidneys from hepatitis Cinfected donors to hepatitis C-negative recipients: Single center experience. Am J Transplant 2019; 19: 3046-3057.
-Ghany MG, Morgan TR. Hepatitis C Guidance 2019 Update: American Association for the Study of Liver Diseases-Infectious Diseases Society of America Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection. Hepatology 2020; 71: 686-721.
Thankyou actually in such a scenario PCR tests are started as early as :
day3-day7 if -ve then
day10 -14 if -ve
6 weeks
in a +ve PCR start DAA within 3-10 days.
some centers would start prophylactically from day0.
Thanks so much, our Prof.
Noted & I agree with you
actually in our center we start prophylactically from D0
Will you accept this DBD donor?
Kidney transplantation from HCV-infected donors to uninfected recipients with immediate or early DAA treatment is associated with excellent viral,
allograft, and patient outcomes (1).
transplanting HCV-infected kidneys into HCV-uninfected recipients is a cost-effective (and often cost-saving) strategy that improves clinical outcomes (2).
So, the answer is Yes, still we can accept the Kidneys from HCV-infected donors to potential recipients based on the available evidence supporting the increased use of organs from HCV-infected DD-like IVDA with early use of DAA therapy that provides a high cure rate and well-tolerated course, also the recipient should receive education and involved in discussion with the necessary information to provide informed consent. Patients should be up-to-date on the risks and benefits of transplantation with an HCV-infected kidney, including the need for DAA treatment, and assuring the availability of the DAA therapy once indicated after transplantation.
If yes, how would you proceed?
Getting an HCV-infected kidney is dependent on factors such as availability of DAA, wait for time, and quality of the organ
Early DAA therapy is preferred before or immediately after transplantation within the first 4 weeks of full 12-week treatment and frequent HCV PCR monitoring till achieving SVR
post-transplant to avoid severe acute HCV infection and also monitor for drug-drug interaction in particular CNI and m TOR inhibitors with DAA therapy due to shared cytochrome P450 metabolism.
DAA course for 1 month costs> 9000 $, its not in our formulary medication in our center, and requesting this treatment through the GI team only.
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. Reddy YNV, Reddy KP, Sise ME. HCV-Infected Deceased Donor Kidney Transplantation-Time to Take Up the Offer. Am J Kidney Dis. 2020 Jun;75(6):827-829.
Well done.
Obviously the availability of DAA is very important for decision making,
1- yes will accept
2- 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
3- we can use basiliximab as induction
4- maintained on tacrolimus, MMF, prednisolone
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
Thankyou.
Yes, I would accept the organ, but a series of precautions are extremely necessary.
1. Knowledge of the potential recipient of the serological status and active disease of the potential donor;
2. Knowledge of the diagnosis and whether there was previous treatment with direct-acting antiviral drugs (DAAA);
– If there was previous treatment and maintenance of the viral load or reinfection by the virus, I would not proceed with the transplant
3. Measurement of viral load;
4. Due to the high risk of disease transmission and the need for induction with rATG (deceased donor) with a triple regimen, I would proceed with Sofosbuvir + Velpastavir (pangenotypic regimen) on D0 of the transplant
5. Serum monitoring of immunosuppressants for possible drug interactions. Avoid sirolimus because it presents an intermediate interaction and measures calcineurin inhibitors.
After sorting out the R as HCV naive how often are you testing his PCR and when are you starting the DAA?
Early treatment is the best choice. I would do PCR one time monthly for the first 3 months and 3-month after treatment in the first year