3. A 46-year-old CKD 5 on HD for the last 5 years due to IgA nephropathy was 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: HsAg negative, HBsAb negative, HBcAb negative, and both HeAg and HBeAb are negative. HCV antibody and HCV PCR are positive (the potential recipient is negative for both). HIV is negative. FCXM is negative.
It is possible for individuals with HCV to donate healthy kidneys, either during their lifetime or after they die. However, it depends on the health of their kidneys.
Previously, people with HCV could not donate kidneys, but this has changed with the availability of direct-acting antiviral (DAA) drugs. These drugs offer cure rates above 95% for people who have contracted the virus and also have chronic kidney disease or end stage renal disease.
· Yes, I will accept this kidney donation offer if there is availability of HCV treatment post renal transplantation because transplanting kidneys from HCV positive donors to recipients with negative HCV will reduce the waiting time on dialysis and enlarge the donation pool.
· Transplanting HCV-viremic to HCV-naive recipients with concomitant DAA therapy that are readily available now can improve outcomes for patients with ESRD.
· The transmission can be prevented by prophylactic DAA therapy and there is a high cure rate for post-transplant patients with established infection.
If yes, how would you proceed?
· The recipient should be counseled and consented before transplantation about the potential risks of HCV infection from an infected donor vs staying on dialysis.
· MDT approach involving a hepatologist and ID to monitor liver functions.
· Ensure availability of DAA agents before proceeding for kidney donation.
· Follow up of liver functions, HCV PCR: at 3-7 days then at day 10-14 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( ledipasvir/sofosbuvir, velpatasvir/sofosbuvir and glecaprevir/pibrentasvir). Follow HCV PCR to confirm SVR seen in most patients.
· Induction immunosuppression: Basiliximab (IL2R) , try to avoid depleting agents (ATG or Almetuzumab).maintenance with triple therapy(steroids, TAC and MMF)
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
This scenario is the same as scenario 2.
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).
I would accept the donor who is both HCV RNA PCR positive and anti HCV Positive…The recipient is negative for both…There is high risk of transmission of HCV from the donor
WE should take proper informed consent and proceed
the recipient should be counselled about the availability of highly active DAA and can cure the HCV infection…Recipient should be counselled about the benefits of transplant as compared to wait on hemodialysis…
I would use IL2 receptor antagonist as induction agent
I would check HCV RNA quantitative at 3 days, 4 weeks, 8 weeks and at 16 weeks after renal transplant…If any of the values are positive patient needs to be started on DAA within 3 days of the result..DAA should be continued for 3 months till SVR is achieved …
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? Donor HCV+ / 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. KDIGO 2022 CLINICAL PRACTICE GUIDELINE For the Prevention, Diagnosis, Evaluation and Treatment of Hepatitis C in CKD recommends – · It is recommended that kidneys from HCV-infected donors be considered regardless of HCV status of potential kidney transplant recipients · It is recommended that the candidate 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.
Transplant candidates are facing incremental mortality risks on the waiting list. Here, we report a novel strategy to expand the donor pool by including hepatitis C seropositive (HCV+) donors. We investigated a pre-exposure prophylactic (PrEP) treatment with direct-acting antivirals (DAA) to allow transplantation for HCV seronegative (HCV-) kidney transplant recipients (KTR) with the aim of preventing HCV infection post-transplantation. In this prospective trial, a pan-genotypic PrEP with daclatasvir and sofosbuvir once daily for 12 week was administered at transplantation. The primary endpoint sustained virological negativity (SVN) 12 weeks after the end of PrEP. Seven patients received transplantation from four HCV+ donors. The accumulated waiting time was 70 ± 31.3 months already. Of note, study subjects underwent transplantation 24.7 ± 16.1 days after given consent. All KTRs developed excellent graft function without any rejection episodes. One patient died with a functioning graft due to sepsis 13 months after transplantation. PrEP demonstrated efficacy with no signs of HCV transmission with excellent tolerability. Two out of four HCV+ donors were viremic at the time of explantation. Interestingly, KTR developed HCV antibodies also from non-viremic donors. The acceptance of HCV+ donors was safe and reduced waiting time under the protection of PrEP DAA in kidney transplantation.
Will you accept this DBD donor?
Yes, i will accept this donor if the recipient has vascular access problems or has been waiting for a long time on the donor waiting list.
We need to counsel the recipient t first about accepting the diseased kidney with all implications; he has to know that he will be on DAA treatment for some time, according to the transplant centre’s protocol.
The recipient should know that this virus will affect the kidney and the liver.
We need to be sure that the recipient has no liver problems.
Criteria to accept this donor include :
First, to know the genotype because genotypes 1 and 3 difficult to treat
Need to know if the donor has any kidney involvement with HCV like proteinuria, nephrites, or cryoglobulinemia, because this will reduce the chance of donation, i will reject the kidney.
If yes, how would you proceed?
yes ,I will proceed for the transplant with a prophylactic approach with Pangetpic DAA.
Pangenotypic DAAs (Elbasvir/grazoprevir) are the preferred antiviral agents, but the cost and availability are the problems.
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
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 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
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 (as the current recipient)
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
If yes, how would you proceed?
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?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.
⭐ ⭐ The index case has been on dialysis for 5 years with expected high morbidity and mortality , so accepting HCV postive donor after counseling, start preemptive DAAV as GZR/EBR immediately before tranplantation and for 3 months thereafter until achieving SVR
This is HCV positive donation to HCV negative recipient , I will proceed to transplantation with DAA therapy ( according to specific HCV genotype ) 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
Will you accept this DBD donor? YES There is high risk of transmission of hepatitis C as donor has Hepatitis C Ab and PCR positive. If DAA are available then I will accept this donor. While doing such transplantation the patient need to be informed and counselled and pros and cons of Kidneys from HCV positive and about DAA. The availability of DAA should be confirmed before such transplantation.
If yes, how would you proceed? DAA should be started soon after transplant so as to avoid liver damage. DAA should be selected as per viral genome type. Adopting a pan genomic therapy is preferred if possible. Induction with Basiliximab rather than ATG id better. Maintenance with triple immune suppressants including TAC, MMF and Prednisolone. Drug levels have to be monitored regulary. HCV PCR at dat 3, 7 14 and at 6 weeks.
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 people with HCV to people without the virus.
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).
A 46-year-old CKD 5 on HD for the last 5 years due to IgA nephropathy was 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: HsAg negative, HBsAb negative, HBcAb negative, and both HeAg and HBeAb are negative.
HCV antibody and HCV PCR are positive (the potential recipient is negative for both).
HIV is negative. FCXM is negative.
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.
3. A 46-year-old CKD 5 on HD for the last 5 years due to IgA nephropathy was 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: HsAg negative, HBsAb negative, HBcAb negative, and both HeAg and HBeAb are negative. HCV antibody and HCV PCR are positive (the potential recipient is negative for both). HIV is negative. FCXM is negative.
A 46-year-old CKD 5 on HD was offered kidneys from a 56 year-old male DBD donor with SAH and S Cr of 65 µmol/L, with HsAg negative, HBsAb negative, HBcAb negative, HCV antibody and HCV PCR positive, HIV negative, and FCXM negative.
Yes I accept this donor
HCV NAT-negative recipients can be safely and successfully transplanted with HCV NAT-positive donor kidneys, reducing waiting time, improving outcomes, and becoming standard of care.
Mixed-genotype infection can be successfully treated and HCV organs can expand the organ pool.
Access to DAA and timely administration of therapy is essential to expand the organ pool.
If yes, how would you proceed?
Patients should be knowledgeable about the risks and advantages of kidney transplantation with an HCV infection, including the requirement for DAA therapy and assuring access to the therapy if it is necessary after transplantation.
The most crucial concept is to perform the transplant without direct anti-retroviral therapy (DAA), but with regular post-transplant monitoring of the recipient’s HCV PCR, and to initiate treatment when HCV+..
In reality, PCR tests are initiated in such a circumstance as early as: day 3-day 7 if -ve, thenday 10 -14 if -ve, 6 weeks if p +ve PCR start DAA within 3-10 days.
In certain facilities, preventative measures would begin on day 0.
Collins LF, Chan A, Zheng J, et al. Direct-Acting Antivirals Improve Access to Care and Cure for Patients With HIV and Chronic HCV Infection. Open Forum Infect Dis. 2017;5(1):ofx264. Published 2017 Dec 9. doi:10.1093/ofid/ofx264
Organs from Hepatitis C Virus–Positive Donors List of authors. Emily A. Blumberg, M.D.This editorial was published on April 3, 2019, at NEJM.org.
Hepatitis C-positive donor to negative recipient kidney transplantationTransplant Infectious Disease1 Jun 2021.
Gong S, Schmotzer CL, Zhou L. Evaluation of Quantitative Real-Time PCR as a Hepatitis C Virus Supplementary Test After RIBA Discontinuation. J Clin Lab Anal. 2016;30(5):418-423. doi:10.1002/jcla.21873
This DBD donor has both HCV antibody & HCV RNA positive. This indicates that the donor is viremic & there is a significant risk for disease transmission to the recipient who is negative for both HCV antibody & HCV RNA.
However, shortage of donor supply & the risks of morbidity & mortality associated with long waitlisting while on dialysis, has dictated the use of high-risk donors such as those who are HCV positive.
Data is accumulating regarding 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.
=========================== If yes, how would you proceed?
In the past, patients who received HCV-infected organ transplants were only able to access ineffective interferon-based antiviral regimens, & thus were more likely to have elevated rates of allograft failure & death.
DAA medication became widely available in 2016, allowing transplant trials of HCV-infected kidneys into HCV-uninfected recipients. The majority of these trials reported 100% HCV cure rates and excellent short-term allograft performance.
Before proceeding, I should guarantee access to DAA & timely administration of therapy. An insurance approval process is also important & can be beneficial to the patient.
After transplantation, the patient should be tested for HCV RNA until viremic. A DAA agent will be prescribed based on genotype & insurance approval.
References
RESEARCH LETTER 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 September 20, 2022, Volume 328, Number 11
Will you accept this DBD donor? Yes, I will accept this patient kidneys if there is availability of DAA and had taken inform consent from recipient as there is high risk of transmitting hepatitis C virus infection in the recipient from anti HCV+/PCR+ donors. Moreover, there is longer waiting time of recipient.
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.
See drug interaction. IL2R as an induction agent avoid ATG/alemtuzumab if possible. References 1.(KDIGO guideline) Treatment of HCV in Kidney Transplant Recipient. 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.
Will you accept this DBD donor?
In this case scenario of potential donor with HCV Ab and PCR positive to HCV negative recipient :I will accept the offer if urgent transplantation needed (failed vascular accesses ,morbidity conferred by dialysis) or the patient has a long time on waiting list.
If yes, how would you proceed?
-Confirm HCV status of the potential donor (already HCV PCR positive).
–Assess the presence of HCV-related kidney disease in HCV RNA-positive donors by an evaluation of kidney function, urinalysis for detection of hematuria, proteinuria and check for clinically silent immune-complex glomerulonephritis.
-Suggested preimplantation biopsy of deceased-donor kidney can be used to evaluate the quality of the HCV RNA-positive donor kidney and to exclude pre-existing kidney disease (frozen sections are not reliable for assessment of mesangial cellularity, glomerular capillary wall thickening, and microthrombi and Fixation of the biopsy specimen in formalin typically takes four to five hours which increased the cold ischemia time).
–The 2018 (KDIGO) guidelines recommend that kidneys from HCV-seropositive/RNA-positive deceased donors should only be given to HCV RNA-positive recipients. However, the use of HCV RNA-positive kidneys in HCV RNA-negative recipients followed by early DAA therapy has been increasingly described in promising pilot trials and reports of single centre experiences.
-Consented HCV negative recipient. -Test recipient for HCV PCR after 3,10 days the 6 weeks if still negative reassure .If PCR came positive >> Confirm PCR>> Positive ,commence DAAs within 3-10 days of the first positive PCR.
A 46 years old, IgA nephropathy induced end stage renal disease, 5 years on HD, recipient, with negative HCV, HIV , and HBV. 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. 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. 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, and the availability of new drugs DAA with sustained viral response reaching 100%.
In the index case with negative FCXM (flowcytometry cross macth), there is no need for induction therapy, thus low risk of infection, so I would do transplant without starting direct anti retroviral therapy(DAA), but frequent monitoring post-transplant of the recipient HCV PCR, and start treatment when HCV+. I’ll consider less drug-drug interaction maintenance immunosuppressive therapy (tacrolimus +MMF +prednisolone) with frequent monitoring of drug level and kidney function. References: (1) Blumberg EA. Organs from Hepatitis C Virus-Positive Donors. N Engl J Med. 2019 Apr 25;380(17):1669-1670. doi: 10.1056/NEJMe1901957. Epub 2019 Apr 3. PMID: 30946554. (2) 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. (3) Kahn JA. The use of organs from hepatitis C virus-viremic donors into uninfected recipients. Curr Opin Organ Transplant. 2020 Dec;25(6):620-625. doi: 10.1097/MOT.0000000000000826. PMID: 33105203. (4) 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. (5) Edmonds C, Carver A, DeClercq J, Choi L, Peter M, Schlendorf K, Perri R, Forbes RC, Concepcion BP. Access to hepatitis C direct-acting antiviral therapy in hepatitis C-positive donor to hepatitis C-negative recipient solid-organ transplantation in a real-world setting. Am J Surg. 2022 May;223(5):975-982. doi: 10.1016/j.amjsurg.2021.09.005. Epub 2021 Sep 14. PMID: 34548142.
-Will you accept this DBD donor? If yes, how would you proceed?
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.
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 is essential part of the transplant procedure. This patient has a chance to achieve SVR12 which will minimize the risk of HCV infection. He should be monitored closely for early defection of any new events and for the response to DAA therapy
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
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)
We recommend that kidney transplant recipients being treated with DAAs be evaluated for the need for dose adjustments of concomitant immunosuppressants (1C)
We suggest that 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.
We recommend treatment with a DAA regimen in patients with post-transplant HCV-associated glomerulonephritis
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
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
Interpretation this Donor according virology report: HBsAg / HBsAb / HBcAb / HBeAg / HBeAb –—– (negative) HCV Ab (positive) / HCV PCR (positive) HIV (negative)
This Donor is negative to (HBV& HIV) but has (HCVAb&PCR positive) My impression;
(Donor with active HCV infection against un infected Recipient) 1-Will you accept this DBD donor? Yes; I will accept this DBD donor -Keep in mind; Post-transplant HCV treatment
PROS;
• Accept HCV-positive donors and fibrosing cholestatic hepatitis following transplant
• Shorter wait-list time
• Increase kidney donor pool
Cons;
• Still at risk of progressive liver disease
• Still at risk of hepatocellular carcinoma
• Longer wait for treatment of HCV post-transplant may leave them at risk of diabetes, graft failure, decreased survival. 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? 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 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.
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
yes as long as DAAs are available and there are no serious comorbidities.
If yes, how would you proceed?
informed consent by the recipient that there is a significant risk of HCV transmission.
DAAs prophylaxis should be done either 12 hours pre-transplantation or on day 0 post-transplantation or with evidence of viremia.
DAAs should be continued for 12 weeks.
caution should be applied for the drug-drug interaction with the following DAAs: Elbasvir/Grazoprevir, Paritaprevir/Ombitasvir and Simeprevir-based combination.
follow-up for HCV PCR test until the highly possible clearance of the virus.
Hepatologist and infectious diseases specialist should be included in the management.
yes, the graft can be accepted after informed consent by the patient and also the availability of DAAs to be given post-transplant.
If yes, how would you proceed?
DAAs can be started either 12 hours before transplantation or on day 0 post-transplantation or 3 days after transplantation.
DAAs should be continued for 12 weeks.
drug-drug interactions should be considered for certain DAAs regimens as Grazoprevir/Elbasvir, Paritaprevir/Ombitasvir and Simeprevir containing regimens
In this scenario, I will accept the offer of transplanting HCV seropositive donor to HCV negative recipient because it will reduce waiting times on the transplant list and improve long-term outcomes. Before the emergence of direct-acting antiviral (DAA) therapy era, Transplantation of a kidney from a donor with chronic HCV infection had been associated with increased morbidity and mortality in kidney transplant recipients without HCV infection. Previously use of pegylated interferon as treatment of HCV infection after transplantation was increasing the risk of rejection.
The high cure rates achieved with DAA therapy have been investigated with multiple trials regarding management of kidneys from HCV RNA-positive donors to HCV RNA-negative patients, which followed by clearance of the virus and establish sustained virologic response (SVR).
If yes, how would you proceed?
For sure, Transplantation of a kidney from a hepatitis C virus (HCV)-infected kidney donor may cause HCV infection in the recipient. The risk of infection must be discussed with the recipient prior to transplantation. Transmission of infection is rare by organ itself, it happened with blood remnants. The decision to accept the offer depends on the anticipated time on the deceased organ waiting list, and morbidity conferred by dialysis. The plan for recipient is early or pre-emptive DAA therapy with close screening of HCV by PCR. Administration of DAAs around the time of transplantation minimizes the risk of chronic HCV infection in the recipient and potentially reduce waiting times and increase the organ supply by making HCV-infected kidneys available for transplantation. A delay in initiation of HCV therapy may be associated with an increased incidence of cytomegalovirus and BK polyomavirus viremia, de novo donor-specific antibodies (DSA), and fibrosing cholestatic hepatitis, which have been reported in some studies.
Will you accept this DBD donor?
Yes, the patient has been waiting for a transplant for five years, and remaining on the waiting list progressively increases their mortality and the transplant is the gold standard method of treatment.
With current knowledge and medications, the control of hepatitis C is possible in a sustained manner and without further impairment of renal and graft function.
If yes, how would you proceed?
The ideal would be to start the scheme with medications against hepatitis C on day 0, avoiding the use of Interferon.
In our service, the standard regimen is Sofosbuvir with Ledispavir, without the need for correction of renal function and with fewer interactions with calcineurin inhibitors and an intermediate for Sirolimus.
If it is not possible to start treatment immediately, frequently check the viral load for the Hepatitis C virus due to the high risk of disease activation. Dosage of calcineurin inhibitors should be performed more frequently due to the possibility of drug interaction.
Yes, new findings show the safety of transplanting kidneys from HCV RNA-positive donors into HCV-negative recipients with early or pre-emptive DAA treatment. advocate using kidneys from high-risk dead donors in uninfected patients where medical necessity is urgent and benefits exceed hazards. In all such circumstances, the receiver should get particular counseling, be educated, and participate in decision-making.
If yes, how would you proceed?
Kidneys from HCV-infected donors can be offered to potential recipients regardless of HCV status, provided that national or regional laws and regulations allow this practice
Kidney transplantation from HCV-infected donors to uninfected recipients with immediate or early DAA treatment is associated with excellent viral, allograft, and patient outcomes
When transplanting kidneys from HCV-infected donors into HCV-uninfected recipients, transplant centers must ensure that recipients 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-positive kidney, including the need for DAA treatment. Transplant centers should confirm the availability of DAAs to be administered to recipients in the early post-transplant period.
Start pan-genotypic DAA directly, until the genotype analysis appears.
Close monitoring of PCR(HCV) RNA(3rd,7th, 14 day, and 6 weeks) and LFTs post-transplant.
References: KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease.
Thanks Do not forget to check that the donor has no HCV-associated nephritis. DAA changed the outcome and made it possible. It is important to discuss it with the patient also as you mentioned.
Will you accept this DBD donor?
Yes if
· Willingness of recipient
· 5 years of maintenance hemodialysis/ long time on waiting list
· DAAs as prophylactic/ treatment
In this particular case we will prefer to accept graft from seropositive/RNA positive donor but it done not applied generally. Though some centers are considering it to increase donor pool. [1] Early trials found that the administration of DAAs for 12 weeks, either prophylactically (first dose given pre transplant) or upon detection of HCV RNA after transplantation, prevented chronic HCV infection in all recipients, and patients maintained overall good kidney allograft function without experiencing acute rejection.[2, 3] If yes, how would you proceed? After willingness of recipient; 1. Proceed with transplantation after work up for liver pathology, apparently he is disease free. 2. Counsel him regarding possible need of DAAs. 3. Check his HCV RNA starting on day 3rd of surgery, then 2nd and 6th week. 4. DAAs if labs work suggestive of HCV infection for at least 12 weeks, either pangenotypic or genotype specific regimen.
References
1. Sise ME, Chute DF, Gustafson JL, Wojciechowski D, Elias N, Chung RT, Williams WW. Transplantation of hepatitis C virus infected kidneys into hepatitis C virus uninfected recipients. Hemodial Int. 2018 Apr;22 Suppl 1:S71-S80. doi: 10.1111/hdi.12650. PMID: 29694722.
2. 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 Apr 17;168(8):533-540. doi: 10.7326/M17-2871. Epub 2018 Mar 6. PMID: 29507971; PMCID: PMC6108432.
3. Sise ME, Strohbehn IA, Chute DF, Gustafson J, Van Deerlin VM, Smith JR, Gentile C, Wojciechowski D, Williams WW, Elias N, Chung RT. Preemptive Treatment With Elbasvir and Grazoprevir for Hepatitis C-Viremic Donor to Uninfected Recipient Kidney Transplantation. Kidney Int Rep. 2020 Jan 13;5(4):459-467. doi: 10.1016/j.ekir.2020.01.001. PMID: 32280841; PMCID: PMC7136432.
Yes, I will access this DBD on account of the following
it will shorten the waiting time
reduce the risk of mortality on dialysis
there is the availability of well-tolerated drugs for HCV infection
good functioning kidney
There is a clear economic and health cost to using HCV positive organ than remaining on dialysis
it reduces the gap between the organ needed and the organ available
studies like THINKER, EXPANDER, and MYTHIC trials have shown positive outcomes in using HCV D+/R-
If yes, how would you proceed?
Obtained informed consent from the recipient on the advantages and the risk of the donor organ. If possible this should be done during the time putting the recipient on the waitlist and it is done again when the organ is available.
The genotype of the HCV infection in the donor
We must rule out the presence of advanced fibrosis or cirrhosis in the recipient using AST to platelet ratio and liver ultrasound
The availability of a regular supply of DAA for the recipient
Check for HCV PCR, on days 3 to 7, days 10 -14, and 6 weeks post-surgery if previous tests are negative
Commencement of DAA within 3- 10 working days of any of the above tests shows HCV PCR positive and it will be for 12 weeks
Also confirmatory and the genotype test of the HCV will be done
References
UK Position Statement on the use of Organs from Hepatitis C Viraemic Donors and Increased Infectious Risk Donors in Hepatitis C Negative Recipients. BTS
May A. Hassabalah. Kidney transplantation in HCV patient. Lecture
Ronit Patnaik, Eugenia Tsai. Hepatitis C Virus Treatment and Solid Organ Transplantation. Gastroenterology &Hepatology. 2022;18(2): 85-92
Thanks Isaac The recipient is HCV negative. Basically, we are talking about HCV positive to negative. Do you need to rule out advanced liver fibrosis in the recipient?
Thank you prof Halawa for your response,
Yes, I will like to rule out advanced liver fibrosis in the recipient as the presence will be a contraindication to going ahead with the transplantation.
Investigations like ultrasound, fibroscan and liver biopsy will be of help,
-In 2 reports , among recipients of organs from HCV-seropositive donors , 14-100% tested +ve for HCVAb after the Tx , 56-96% tested +ve for HCV RNA by PCR .
-Recipients of kidneys from HCV +ve donors have decreased survival compared to those who receive kidneys from non- HCV +ve donors but better survival compared to those on the waiting list .
-The decision to accept a kidney from a deceased donor who’s seropositive/RNA +ve HCV depends on various recipient factors :
-Recipient HCV status
-The anticipated time on the waiting list
-Morbidity conferred by dialysis
-It should be noted that the 2018 KDIGO guidelines recommend that kidneys from HCV seropositive and HCV RNA +ve (as the case here in our potential deceased donor ) should only be given to HCV RNA +ve recipient .
-Although transplantation of kidneys from HCV Sero+ve, RNA+ve donors to HCV-ve recipients has traditionally not been performed , administration of effective DAA’s around the time of Tx minimizes the risk of chronic HCV infection in the recipient , and could potentially decrease the waiting times and increase the organ supply and avoid the discarding of high quality kidneys from HCV+ve deceased donors , so as a result several Tx centers started to adopt this idea .
-Certain issues need to be addressed and pointed clear including :
1-The DAA regimen
2-Timing of the DAA therapy
3-Management plan of possible relapse
4-Assurance of access to DAA therapy
I will proceed with this Tx , HCV antibody and RNA PCR check for the recipient post Tx 3-7 days , 10-14 days , 6 weeks if -ve we manage as regular recipient , if +ve we start DAA’s at 3-10 days of the 1st +ve PCR
It is possible for individuals with HCV to donate healthy kidneys, either during their lifetime or after they die. However, it depends on the health of their kidneys.
Previously, people with HCV could not donate kidneys, but this has changed with the availability of direct-acting antiviral (DAA) drugs. These drugs offer cure rates above 95% for people who have contracted the virus and also have chronic kidney disease or end stage renal disease.
Will you accept this DBD donor?
· Similar to the Above scenario
· Yes, I will accept this kidney donation offer if there is availability of HCV treatment post renal transplantation because transplanting kidneys from HCV positive donors to recipients with negative HCV will reduce the waiting time on dialysis and enlarge the donation pool.
· Transplanting HCV-viremic to HCV-naive recipients with concomitant DAA therapy that are readily available now can improve outcomes for patients with ESRD.
· The transmission can be prevented by prophylactic DAA therapy and there is a high cure rate for post-transplant patients with established infection.
If yes, how would you proceed?
· The recipient should be counseled and consented before transplantation about the potential risks of HCV infection from an infected donor vs staying on dialysis.
· MDT approach involving a hepatologist and ID to monitor liver functions.
· Ensure availability of DAA agents before proceeding for kidney donation.
· Follow up of liver functions, HCV PCR: at 3-7 days then at day 10-14 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( ledipasvir/sofosbuvir, velpatasvir/sofosbuvir and glecaprevir/pibrentasvir). Follow HCV PCR to confirm SVR seen in most patients.
· Induction immunosuppression: Basiliximab (IL2R) , try to avoid depleting agents (ATG or Almetuzumab).maintenance with triple therapy(steroids, TAC and MMF)
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, et al. Control of replication of hepatitis B and C virus improves patient and graft survival in kidney transplantation. J Hepatol 2019; 70:831.
3. Teperman L. Hepatitis C-positive donor to negative recipient kidney transplantation: A real-world experience. Transpl Infect Dis. 2021 Jun;23(3):e13540.
this scenario is the same as scenario 2.
This scenario is the same as scenario 2.
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).
I would accept the donor who is both HCV RNA PCR positive and anti HCV Positive…The recipient is negative for both…There is high risk of transmission of HCV from the donor
WE should take proper informed consent and proceed
the recipient should be counselled about the availability of highly active DAA and can cure the HCV infection…Recipient should be counselled about the benefits of transplant as compared to wait on hemodialysis…
I would use IL2 receptor antagonist as induction agent
I would check HCV RNA quantitative at 3 days, 4 weeks, 8 weeks and at 16 weeks after renal transplant…If any of the values are positive patient needs to be started on DAA within 3 days of the result..DAA should be continued for 3 months till SVR is achieved …
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?
Donor HCV+ / 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.
KDIGO 2022 CLINICAL PRACTICE GUIDELINE For the Prevention, Diagnosis, Evaluation and Treatment of Hepatitis C in CKD recommends –
· It is recommended that kidneys from HCV-infected donors be considered regardless of HCV status of potential kidney transplant recipients
· It is recommended that the candidate 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.
Same answer like scenerio 2
Same Answer Prof as of Scenerio 2 please
Transplant candidates are facing incremental mortality risks on the waiting list. Here, we report a novel strategy to expand the donor pool by including hepatitis C seropositive (HCV+) donors. We investigated a pre-exposure prophylactic (PrEP) treatment with direct-acting antivirals (DAA) to allow transplantation for HCV seronegative (HCV-) kidney transplant recipients (KTR) with the aim of preventing HCV infection post-transplantation. In this prospective trial, a pan-genotypic PrEP with daclatasvir and sofosbuvir once daily for 12 week was administered at transplantation. The primary endpoint sustained virological negativity (SVN) 12 weeks after the end of PrEP. Seven patients received transplantation from four HCV+ donors. The accumulated waiting time was 70 ± 31.3 months already. Of note, study subjects underwent transplantation 24.7 ± 16.1 days after given consent. All KTRs developed excellent graft function without any rejection episodes. One patient died with a functioning graft due to sepsis 13 months after transplantation. PrEP demonstrated efficacy with no signs of HCV transmission with excellent tolerability. Two out of four HCV+ donors were viremic at the time of explantation. Interestingly, KTR developed HCV antibodies also from non-viremic donors. The acceptance of HCV+ donors was safe and reduced waiting time under the protection of PrEP DAA in kidney transplantation.
Yes, i will accept this donor if the recipient has vascular access problems or has been waiting for a long time on the donor waiting list.
We need to counsel the recipient t first about accepting the diseased kidney with all implications; he has to know that he will be on DAA treatment for some time, according to the transplant centre’s protocol.
The recipient should know that this virus will affect the kidney and the liver.
We need to be sure that the recipient has no liver problems.
Criteria to accept this donor include :
First, to know the genotype because genotypes 1 and 3 difficult to treat
Need to know if the donor has any kidney involvement with HCV like proteinuria, nephrites, or cryoglobulinemia, because this will reduce the chance of donation, i will reject the kidney.
yes ,I will proceed for the transplant with a prophylactic approach with Pangetpic DAA.
referrence
uptodate
same answer as case scenario 2 .
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:
If yes, how would you proceed?
References
1- Utilization of HCV viremic donors in kidney transplantation: a chance or a threat?
Thanks
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.
Dear All
This is a similar scenario to scenario 2. Please do not reply here.
⭐ ⭐ The index case has been on dialysis for 5 years with expected high morbidity and mortality , so accepting HCV postive donor after counseling, start preemptive DAAV as GZR/EBR immediately before tranplantation and for 3 months thereafter until achieving SVR
Dear All
This is a similar scenario to scenario 2. Please do not reply here.
Yes I will accept this DBD
This is HCV positive donation to HCV negative recipient , I will proceed to transplantation with DAA therapy ( according to specific HCV genotype ) 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
Dear All
This is a similar scenario to scenario 2. Please do not reply here.
Will you accept this DBD donor?
YES
There is high risk of transmission of hepatitis C as donor has Hepatitis C Ab and PCR positive. If DAA are available then I will accept this donor. While doing such transplantation the patient need to be informed and counselled and pros and cons of Kidneys from HCV positive and about DAA.
The availability of DAA should be confirmed before such transplantation.
If yes, how would you proceed?
DAA should be started soon after transplant so as to avoid liver damage. DAA should be selected as per viral genome type. Adopting a pan genomic therapy is preferred if possible.
Induction with Basiliximab rather than ATG id better.
Maintenance with triple immune suppressants including TAC, MMF and Prednisolone. Drug levels have to be monitored regulary. HCV PCR at dat 3, 7 14 and at 6 weeks.
Dear All
This is a similar scenario to scenario 2. Please do not reply here.
Dear All
This is a similar scenario to scenario 2. Please do not reply here.
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 people with HCV to people without the virus.
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).
Thank you
A 46-year-old CKD 5 on HD for the last 5 years due to IgA nephropathy was 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: HsAg negative, HBsAb negative, HBcAb negative, and both HeAg and HBeAb are negative.
HCV antibody and HCV PCR are positive (the potential recipient is negative for both).
HIV is negative. FCXM is negative.
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.
Thank you
3. A 46-year-old CKD 5 on HD for the last 5 years due to IgA nephropathy was 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: HsAg negative, HBsAb negative, HBcAb negative, and both HeAg and HBeAb are negative. HCV antibody and HCV PCR are positive (the potential recipient is negative for both). HIV is negative. FCXM is negative.
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Will you accept this DBD donor?
History
Yes I accept this donor
If yes, how would you proceed?
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Reference
Thank you Dr Mahmoud
Many thanks for you Prof.Halawa
Yes i aacept
FXM negative but not mentioned any thing about DSA
induction with basiliximab
treatment with antiviral post transplantation for 12 weeks and monitoring
Dalshad
Your answer is quite often short. Please expand
Will you accept this DBD donor?
===========================
If yes, how would you proceed?
References
Will you accept this DBD donor?
Yes, I will accept this patient kidneys if there is availability of DAA and had taken inform consent from recipient as there is high risk of transmitting hepatitis C virus infection in the recipient from anti HCV+/PCR+ donors. Moreover, there is longer waiting time of recipient.
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.
See drug interaction.
IL2R as an induction agent avoid ATG/alemtuzumab if possible.
References
1.(KDIGO guideline) Treatment of HCV in Kidney Transplant Recipient.
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.
Will you accept this DBD donor?
In this case scenario of potential donor with HCV Ab and PCR positive to HCV negative recipient :I will accept the offer if urgent transplantation needed (failed vascular accesses ,morbidity conferred by dialysis) or the patient has a long time on waiting list.
If yes, how would you proceed?
-Confirm HCV status of the potential donor (already HCV PCR positive).
–Assess the presence of HCV-related kidney disease in HCV RNA-positive donors by an evaluation of kidney function, urinalysis for detection of hematuria, proteinuria and check for clinically silent immune-complex glomerulonephritis.
-Suggested preimplantation biopsy of deceased-donor kidney can be used to evaluate the quality of the HCV RNA-positive donor kidney and to exclude pre-existing kidney disease (frozen sections are not reliable for assessment of mesangial cellularity, glomerular capillary wall thickening, and microthrombi and Fixation of the biopsy specimen in formalin typically takes four to five hours which increased the cold ischemia time).
–The 2018 (KDIGO) guidelines recommend that kidneys from HCV-seropositive/RNA-positive deceased donors should only be given to HCV RNA-positive recipients. However, the use of HCV RNA-positive kidneys in HCV RNA-negative recipients followed by early DAA therapy has been increasingly described in promising pilot trials and reports of single centre experiences.
-Consented HCV negative recipient.
-Test recipient for HCV PCR after 3,10 days the 6 weeks if still negative reassure .If PCR came positive >> Confirm PCR>> Positive ,commence DAAs within 3-10 days of the first positive PCR.
A 46 years old, IgA nephropathy induced end stage renal disease, 5 years on HD, recipient, with negative HCV, HIV , and HBV.
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.
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.
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, and the availability of new drugs DAA with sustained viral response reaching 100%.
In the index case with negative FCXM (flowcytometry cross macth), there is no need for induction therapy, thus low risk of infection, so I would do transplant without starting direct anti retroviral therapy(DAA), but frequent monitoring post-transplant of the recipient HCV PCR, and start treatment when HCV+.
I’ll consider less drug-drug interaction maintenance immunosuppressive therapy (tacrolimus +MMF +prednisolone) with frequent monitoring of drug level and kidney function.
References:
(1) Blumberg EA. Organs from Hepatitis C Virus-Positive Donors. N Engl J Med. 2019 Apr 25;380(17):1669-1670. doi: 10.1056/NEJMe1901957. Epub 2019 Apr 3. PMID: 30946554.
(2) 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.
(3) Kahn JA. The use of organs from hepatitis C virus-viremic donors into uninfected recipients. Curr Opin Organ Transplant. 2020 Dec;25(6):620-625. doi: 10.1097/MOT.0000000000000826. PMID: 33105203.
(4) 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.
(5) Edmonds C, Carver A, DeClercq J, Choi L, Peter M, Schlendorf K, Perri R, Forbes RC, Concepcion BP. Access to hepatitis C direct-acting antiviral therapy in hepatitis C-positive donor to hepatitis C-negative recipient solid-organ transplantation in a real-world setting. Am J Surg. 2022 May;223(5):975-982. doi: 10.1016/j.amjsurg.2021.09.005. Epub 2021 Sep 14. PMID: 34548142.
-Will you accept this DBD donor? If yes, how would you proceed?
Reference:
Will you accept this donor and how would you proceed?
KDIGO guidelines on HCV (2022) mention that –
BTS guidelines mention that:
UK Position Statement on the use of Organs from Hepatitis C Viraemic Donors and Increased Infectious Risk Donors in Hepatitis C Negative Recipients
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
Interpretation this Donor according virology report:
HBsAg / HBsAb / HBcAb / HBeAg / HBeAb –—– (negative)
HCV Ab (positive) / HCV PCR (positive)
HIV (negative)
This Donor is negative to (HBV& HIV) but has (HCVAb&PCR positive)
My impression;
(Donor with active HCV infection against un infected Recipient)
1-Will you accept this DBD donor?
Yes; I will accept this DBD donor
-Keep in mind;
Post-transplant HCV treatment
PROS;
• Accept HCV-positive donors and fibrosing cholestatic hepatitis following transplant
• Shorter wait-list time
• Increase kidney donor pool
Cons;
• Still at risk of progressive liver disease
• Still at risk of hepatocellular carcinoma
• Longer wait for treatment of HCV post-transplant may leave them at risk of diabetes, graft failure, decreased survival.
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?
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 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.
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
Will you accept this DBD donor?
If yes, how would you proceed?
Will you accept this DBD donor?
If yes, how would you proceed?
sorry for repeating. it was due to system lag
Will you accept this DBD donor?
In this scenario, I will accept the offer of transplanting HCV seropositive donor to HCV negative recipient because it will reduce waiting times on the transplant list and improve long-term outcomes. Before the emergence of direct-acting antiviral (DAA) therapy era, Transplantation of a kidney from a donor with chronic HCV infection had been associated with increased morbidity and mortality in kidney transplant recipients without HCV infection. Previously use of pegylated interferon as treatment of HCV infection after transplantation was increasing the risk of rejection.
The high cure rates achieved with DAA therapy have been investigated with multiple trials regarding management of kidneys from HCV RNA-positive donors to HCV RNA-negative patients, which followed by clearance of the virus and establish sustained virologic response (SVR).
If yes, how would you proceed?
For sure, Transplantation of a kidney from a hepatitis C virus (HCV)-infected kidney donor may cause HCV infection in the recipient. The risk of infection must be discussed with the recipient prior to transplantation. Transmission of infection is rare by organ itself, it happened with blood remnants. The decision to accept the offer depends on the anticipated time on the deceased organ waiting list, and morbidity conferred by dialysis.
The plan for recipient is early or pre-emptive DAA therapy with close screening of HCV by PCR. Administration of DAAs around the time of transplantation minimizes the risk of chronic HCV infection in the recipient and potentially reduce waiting times and increase the organ supply by making HCV-infected kidneys available for transplantation. A delay in initiation of HCV therapy may be associated with an increased incidence of cytomegalovirus and BK polyomavirus viremia, de novo donor-specific antibodies (DSA), and fibrosing cholestatic hepatitis, which have been reported in some studies.
References:
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.
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.
Will you accept this DBD donor?
Yes, the patient has been waiting for a transplant for five years, and remaining on the waiting list progressively increases their mortality and the transplant is the gold standard method of treatment.
With current knowledge and medications, the control of hepatitis C is possible in a sustained manner and without further impairment of renal and graft function.
If yes, how would you proceed?
The ideal would be to start the scheme with medications against hepatitis C on day 0, avoiding the use of Interferon.
In our service, the standard regimen is Sofosbuvir with Ledispavir, without the need for correction of renal function and with fewer interactions with calcineurin inhibitors and an intermediate for Sirolimus.
If it is not possible to start treatment immediately, frequently check the viral load for the Hepatitis C virus due to the high risk of disease activation. Dosage of calcineurin inhibitors should be performed more frequently due to the possibility of drug interaction.
Yes, new findings show the safety of transplanting kidneys from HCV RNA-positive donors into HCV-negative recipients with early or pre-emptive DAA treatment. advocate using kidneys from high-risk dead donors in uninfected patients where medical necessity is urgent and benefits exceed hazards. In all such circumstances, the receiver should get particular counseling, be educated, and participate in decision-making.
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.
Thanks
Do not forget to check that the donor has no HCV-associated nephritis. DAA changed the outcome and made it possible. It is important to discuss it with the patient also as you mentioned.
Will you accept this DBD donor?
Yes if
· Willingness of recipient
· 5 years of maintenance hemodialysis/ long time on waiting list
· DAAs as prophylactic/ treatment
In this particular case we will prefer to accept graft from seropositive/RNA positive donor but it done not applied generally. Though some centers are considering it to increase donor pool. [1] Early trials found that the administration of DAAs for 12 weeks, either prophylactically (first dose given pre transplant) or upon detection of HCV RNA after transplantation, prevented chronic HCV infection in all recipients, and patients maintained overall good kidney allograft function without experiencing acute rejection.[2, 3]
If yes, how would you proceed?
After willingness of recipient;
1. Proceed with transplantation after work up for liver pathology, apparently he is disease free.
2. Counsel him regarding possible need of DAAs.
3. Check his HCV RNA starting on day 3rd of surgery, then 2nd and 6th week.
4. DAAs if labs work suggestive of HCV infection for at least 12 weeks, either pangenotypic or genotype specific regimen.
References
1. Sise ME, Chute DF, Gustafson JL, Wojciechowski D, Elias N, Chung RT, Williams WW. Transplantation of hepatitis C virus infected kidneys into hepatitis C virus uninfected recipients. Hemodial Int. 2018 Apr;22 Suppl 1:S71-S80. doi: 10.1111/hdi.12650. PMID: 29694722.
2. 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 Apr 17;168(8):533-540. doi: 10.7326/M17-2871. Epub 2018 Mar 6. PMID: 29507971; PMCID: PMC6108432.
3. Sise ME, Strohbehn IA, Chute DF, Gustafson J, Van Deerlin VM, Smith JR, Gentile C, Wojciechowski D, Williams WW, Elias N, Chung RT. Preemptive Treatment With Elbasvir and Grazoprevir for Hepatitis C-Viremic Donor to Uninfected Recipient Kidney Transplantation. Kidney Int Rep. 2020 Jan 13;5(4):459-467. doi: 10.1016/j.ekir.2020.01.001. PMID: 32280841; PMCID: PMC7136432.
Thanks Faraman
Do not forget to check that the donor has no HCV-associated nephritis
Will you accept this DBD donor?
Yes, I will access this DBD on account of the following
If yes, how would you proceed?
References
Thanks Isaac
The recipient is HCV negative. Basically, we are talking about HCV positive to negative. Do you need to rule out advanced liver fibrosis in the recipient?
Thank you prof Halawa for your response,
Yes, I will like to rule out advanced liver fibrosis in the recipient as the presence will be a contraindication to going ahead with the transplantation.
Investigations like ultrasound, fibroscan and liver biopsy will be of help,
-In 2 reports , among recipients of organs from HCV-seropositive donors , 14-100% tested +ve for HCVAb after the Tx , 56-96% tested +ve for HCV RNA by PCR .
-Recipients of kidneys from HCV +ve donors have decreased survival compared to those who receive kidneys from non- HCV +ve donors but better survival compared to those on the waiting list .
-The decision to accept a kidney from a deceased donor who’s seropositive/RNA +ve HCV depends on various recipient factors :
-Recipient HCV status
-The anticipated time on the waiting list
-Morbidity conferred by dialysis
-It should be noted that the 2018 KDIGO guidelines recommend that kidneys from HCV seropositive and HCV RNA +ve (as the case here in our potential deceased donor ) should only be given to HCV RNA +ve recipient .
-Although transplantation of kidneys from HCV Sero+ve, RNA+ve donors to HCV-ve recipients has traditionally not been performed , administration of effective DAA’s around the time of Tx minimizes the risk of chronic HCV infection in the recipient , and could potentially decrease the waiting times and increase the organ supply and avoid the discarding of high quality kidneys from HCV+ve deceased donors , so as a result several Tx centers started to adopt this idea .
-Certain issues need to be addressed and pointed clear including :
1-The DAA regimen
2-Timing of the DAA therapy
3-Management plan of possible relapse
4-Assurance of access to DAA therapy
I will proceed with this Tx , HCV antibody and RNA PCR check for the recipient post Tx 3-7 days , 10-14 days , 6 weeks if -ve we manage as regular recipient , if +ve we start DAA’s at 3-10 days of the 1st +ve PCR
References :
1- Up-to-date -Seropositive donor to seronegative recipient renal transplants
2- BTS HCV statement
HCV positive to HCV negative has been recently done under the umbrella of DAA. You have used old references