|Year : 2018 | Volume
| Issue : 3 | Page : 227-229
Successful outcome of transplanting a kidney from a HCV-positive deceased donor into a HCV-negative recipient
Zaheer Amin Virani, Prashant J Rajput, Hepal M Vora, Mita B Shah, Samir Shah, Bharat V Shah
Department of Nephrology, Institute of Renal Sciences, Global Hospital, Mumbai, Maharashtra, India
|Date of Web Publication||28-Sep-2018|
Dr. Bharat V Shah
Institute of Renal Sciences, Global Hospital, Parel, Mumbai, Maharashtra
Source of Support: None, Conflict of Interest: None
The discovery of direct-acting antiviral therapy has revolutionized the treatment of Hepatitis C infection. The treatment of choice in a case of end stage kidney disease with Hepatitis C infection is kidney transplant and with DAA based interferon free regimens one can treat post transplant as well. There is paucity of data regarding transplantation of kidneys from HCV-infected donors into HCV-negative recipients. We report a case of sequential liver and kidney transplantation in which a HCV-negative recipient received a kidney from a HCV-infected deceased donor.
Keywords: Deceased donor kidney transplant, directly acting antiviral agents, hepatitis C virus positive, liver and kidney transplant
|How to cite this article:|
Virani ZA, Rajput PJ, Vora HM, Shah MB, Shah S, Shah BV. Successful outcome of transplanting a kidney from a HCV-positive deceased donor into a HCV-negative recipient. Indian J Transplant 2018;12:227-9
|How to cite this URL:|
Virani ZA, Rajput PJ, Vora HM, Shah MB, Shah S, Shah BV. Successful outcome of transplanting a kidney from a HCV-positive deceased donor into a HCV-negative recipient. Indian J Transplant [serial online] 2018 [cited 2021 May 18];12:227-9. Available from: https://www.ijtonline.in/text.asp?2018/12/3/227/242436
| Introduction|| |
There is a marked scarcity of kidneys for transplantation and a high mortality among patients on the waiting list for kidney transplants. This problem is even more severe in India where deceased donor renal transplantation is still poor (constituting <5% of the total renal transplants), and dialysis treatment is far from adequate. The extreme shortage of kidneys has led some centers to accept kidneys that carry elevated risks of transmitting infections. Most transplant teams often discard kidneys from donors with hepatitis C virus (HCV) infection if the recipients are HCV negative because there is a high risk of transmitting HCV by organ transplantation as shown by Pereira et al. With availability of direct-acting antiviral (DAA) therapy with high cure rates, we have successfully treated an HCV-positive end-stage renal disease patient after a combined liver and kidney transplant. Therefore, we see no reason why kidneys from HCV-positive donors should not be accepted for HCV negative transplant candidates on maintenance dialysis. Indeed, Goldberg et al. have shown that transplantation of HCV kidneys into HCV-negative recipients, followed by the use of DAA agents, can provide excellent allograft function with a cure of HCV infection. This prompted us to accept a kidney from a HCV-positive brain-dead donor for our HCV-negative recipient. To our knowledge, this is the first such case from India.
| Case Report|| |
A 53-year-old male with type 2 diabetes mellitus for 25 years was diagnosed with hepatitis C-positive chronic liver disease in 2007. His HCV infection was possibly due to blood transfusions he had received in the past.
In January 2011, his chronic liver disease decompensated. He was treated for HCV with interferon and ribavirin. His treatment was interrupted after 6 months as he developed intolerable side effects to the therapy.
On September 20, 2013, he underwent deceased donor liver transplant. He did not receive any induction immunosuppression except methylprednisolone. His maintenance immunosuppression was prednisolone, mycophenolate mofetil (MMF), and tacrolimus. Subsequently, steroids were discontinued and he was on MMF (250 mg twice a day) and tacrolimus (dose adjusted to maintain tacrolimus level around 5 ng/ml).
In September 2014, he developed edema. Evaluation revealed that he had nephrotic range proteinuria and microscopic hematuria. Serum creatinine was 1.18 mg/dl, and ultrasound of the kidneys was normal. Considering that he had no diabetic retinopathy and that he had diabetes for more than 25 years, a possibility of nondiabetic kidney disease was considered. The C3 complement level was 89 mg/dl; antinuclear antibody and cryoglobulins were negative. A percutaneous kidney biopsy was performed. Light microscopy revealed features of membranoproliferative glomerulonephritis, and immunofluorescence showed predominantly immunoglobulin M and C3 positivity in capillary glomerular loops. This was reported to be consistent with HCV-associated glomerulonephritis. The patient had persistent proteinuria, a relatively rapid rise in creatinine, and by January 2015, his creatinine had risen to 2.8 mg/dl.
In January 2015, the only DAA therapy which was available in India was sofosbuvir. Hence, the patient was treated with sofosbuvir and ribavirin to which he had an excellent response and by 12 weeks, his HCV RNA was undetectable in the blood. After an initial response (serum creatinine dropping from 2.8 to 2.2 mg/dl), his renal function continued to deteriorate and in June 2016, he was initiated on maintenance hemodialysis.
On December 10, 2017, we received a call for a kidney from a HCV-positive brain-dead donor. One kidney was accepted by a center that had a HCV-positive recipient. No center was willing to accept the other kidney. We discussed with the patient about the risk of contracting HCV infection and the possibility of treating infection after transplant. Having been successfully treated for HCV infection in the past, he accepted the offer, signed the informed consent, and the renal transplant was performed. At this time, he had normal liver allograft function.
Induction immunosuppression was methylprednisolone and two doses of basiliximab (20 mg). Maintenance immunosuppression was prednisolone, tacrolimus, and MMF. Later, MMF was replaced by azathioprine as he developed intolerable gastrointestinal side effects.
The donor's hepatitis C viral load was 19,789,048 copies/ml. The recipient's HCV RNA was undetectable before kidney transplant and 1 week after transplant, it was 992,920 copies/ml.
During the period that he was HCV positive, he developed no complications reported to be associated with HCV positivity in kidney transplant patients. His glycemic control remained good as well, without any increase in antihyperglycemic agents.
Once his renal function stabilized and his estimated glomerular filtration rate improved to >30 ml/min/1.73 m2, he was treated with a dual oral regimen of daclatasvir plus sofosbuvir. His viral load was undetectable at 4 weeks and he attained a sustained virologial response (defined as aviremia 24 weeks after completion of antiviral therapy).
| Discussion|| |
Pereira et al. have shown that the high risk of transmitting HCV by organ transplantation and HCV infection post kidney transplant is associated with various complications. Increase in secondary infections,,,, posttransplant diabetes mellitus, lymphoproliferative disorders, myeloma,, risk of hepatocellular carcinoma, liver cirrhosis, and excess of cardiovascular-associated mortality have all been reported with hepatitis C infection postkidney transplant. An overall increased mortality has been reported in uninfected patients who receive kidneys from HCV-infected donors. For the above reasons, most centers are reluctant to accept kidneys from a HCV-positive brain-dead donor for a HCV-negative recipient.
With the new DAAs resulting in sustained virologic response, one would expect such complications to not occur after kidney transplant. The DAAs for HCV are NS5A inhibitors, NS5B inhibitors, and NS3/4A protease inhibitors. Sofosbuvir, the most commonly used DAA, is an NS5B inhibitor, while daclatasvir is a NS5A inhibitor. Interaction with immunosuppressive agents is not expected as sofosbuvir and daclatasvir are not substrates of the cytochrome P450 isoenzymes 3A4/5 or the drug transporter P-glycoprotein.
Treatment with DAAs for HCV postkidney transplantation was reported in two studies. Both used sofosbuvir-based regimens and showed a 100% sustained virological response at 12 weeks. Drugs were well tolerated with no significant adverse events or rejection episodes. Improved hepatic function post-HCV viral clearance was believed to be the cause of posttreatment 45% decrease in tacrolimus trough levels despite no dose reductions in tacrolimus.,
None of the HCV-associated complications were seen during the period our patient was HCV positive. HCV infection is known to have diabetogenic effect by causing insulin resistance, decreased hepatic glucose uptake and glycogenesis, and a direct cytopathic effect of the virus on pancreatic beta-cells. With this, one would expect glycemic control to worsen and need for antihyperglycemic agents to increase. This however was not seen in our patient and in fact his glycemic control was better and requirement of antihyperglycemic agents was lower than that required before kidney transplant.
There has been great debate regarding immunosuppression in HCV-positive recipients. While cyclosporine may have an advantage over tacrolimus as it inhibits the intracellular replication of HCV, independent of its immunosuppressive activity, this antiviral effect remains suspect.,
Data regarding MMF are also conflicting. An increase in viral replication was seen in the study by Rostaing et al., but the USRDS registry reported a better graft survival than in those on other immunosuppressive therapy.
Goldberg et al. in their THINKER trial used standard induction and maintenance immunosuppression with no increase in complications.
In summary, our case shows that transplantation of kidneys from HCV-infected donors into HCV-negative recipients, followed by the use of DAA agents, can provide potentially excellent allograft function with a cure of HCV infection.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understand that names and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Gopalakrishnan N, Dineshkumar T, Dhanapriya J, Sakthirajan R, Balasubramaniyan T, Srinivasa Prasad ND, et al.
Deceased donor renal transplantation: A single center experience. Indian J Nephrol 2017;27:4-8.
] [Full text]
Jha V. Current status of end-stage renal disease care in India and Pakistan. Kidney Int Suppl 2013;3:157-60.
Reese PP, Abt PL, Blumberg EA, Goldberg DS. Transplanting hepatitis C-positive kidneys. N
Engl J Med 2015;373:303-5.
Pereira BJ, Milford EL, Kirkman RL, Levey AS. Transmission of hepatitis C virus by organ transplantation. N
Engl J Med 1991;325:454-60.
Goldberg DS, Abt PL, Blumberg EA, Van Deerlin VM, Levine M, Reddy KR, et al.
Trial of transplantation of HCV-infected kidneys into uninfected recipients. N
Engl J Med 2017;376:2394-5.
Domínguez-Gil B, Morales JM. Transplantation in the patient with hepatitis C. Transpl Int 2009;22:1117-31.
Mitwalli AH, Alam A, Al-Wakeel J, Al Suwaida K, Tarif N, Schaar TA, et al.
Effect of chronic viral hepatitis on graft survival in Saudi renal transplant patients. Nephron Clin Pract 2006;102:c72-80.
Roth D, Gaynor JJ, Reddy KR, Ciancio G, Sageshima J, Kupin W, et al.
Effect of kidney transplantation on outcomes among patients with hepatitis C. J Am Soc Nephrol 2011;22:1152-60.
Morales JM, Campistol JM, Domínguez-Gil B, Andrés A, Esforzado N, Oppenheimer F, et al.
Long-term experience with kidney transplantation from hepatitis C-positive donors into hepatitis C-positive recipients. Am J Transplant 2010;10:2453-62.
Cole EH, Johnston O, Rose CL, Gill JS. Impact of acute rejection and new-onset diabetes on long-term transplant graft and patient survival. Clin J Am Soc Nephrol 2008;3:814-21.
Kondo Y, Shimosegawa T. Direct effects of hepatitis C virus on the lymphoid cells. World J Gastroenterol 2013;19:7889-95.
Takahashi K, Nishida N, Kawabata H, Haga H, Chiba T. Regression of Hodgkin lymphoma in response to antiviral therapy for hepatitis C virus infection. Intern Med 2012;51:2745-7.
Fabrizi F, Martin P, Dixit V, Bunnapradist S, Dulai G. Hepatitis C virus antibody status and survival after renal transplantation: Meta-analysis of observational studies. Am J Transplant 2005;5:1452-61.
Sawinski D, Kaur N, Ajeti A, Trofe-Clark J, Lim M, Bleicher M, et al.
Successful treatment of hepatitis C in renal transplant recipients with direct-acting antiviral agents. Am J Transplant 2016;16:1588-95.
Kamar N, Marion O, Rostaing L, Cointault O, Ribes D, Lavayssière L, et al.
Efficacy and safety of sofosbuvir-based antiviral therapy to treat hepatitis C virus infection after kidney transplantation. Am J Transplant 2016;16:1474-9.
Bloom RD, Lake JR. Emerging issues in hepatitis C virus-positive liver and kidney transplant recipients. Am J Transplant 2006;6:2232-7.
Fabrizi F, Bromberg J, Elli A, Dixit V, Martin P. Review article: Hepatitis C virus and calcineurin inhibition after renal transplantation. Aliment Pharmacol Ther 2005;22:657-66.
Fagiuoli S, Bruni F, Bravi M, Candusso M, Gaffuri G, Colledan M, et al.
Cyclosporin in steroid-resistant autoimmune hepatitis and HCV-related liver diseases. Dig Liver Dis 2007;39 Suppl 3:S379-85.
Morales JM, Campistol JM, Castellano G, Andres A, Colina F, Fuertes A, et al.
Transplantation of kidneys from donors with hepatitis C antibody into recipients with pre-transplantation anti-HCV. Kidney Int 1995;47:236-40.
Rostaing L, Izopet J, Sandres K, Cisterne JM, Puel J, Durand D, et al.
Changes in hepatitis C virus RNA viremia concentrations in long-term renal transplant patients after introduction of mycophenolate mofetil. Transplantation 2000;69:991-4.