Multicenter Study to Transplant Hepatitis C–Infected Kidneys (MYTHIC): An Open-Label Study of Combined Glecaprevir and Pibrentasvir to Treat Recipients of Transplanted Kidneys from Deceased Donors with Hepatitis C Virus Infection

Abstract

BackgroundSingle-center trials and retrospective case series have reported promising outcomes using kidneys from donors with hepatitis C virus (HCV) infection. However, multicenter trials are needed to determine if those findings are generalizable.MethodsWe conducted a prospective trial at seven centers to transplant 30 kidneys from deceased donors with HCV viremia into HCV-uninfected recipients, followed by 8 weeks of once-daily coformulated glecaprevir and pibrentasvir, targeted to start 3 days posttransplant. Key outcomes included sustained virologic response (undetectable HCV RNA 12 weeks after completing treatment with glecaprevir and pibrentasvir), adverse events, and allograft function.ResultsWe screened 76 patients and enrolled 63 patients, of whom 30 underwent kidney transplantation from an HCV-viremic deceased donor (median kidney donor profile index, 53%) in May 2019 through October 2019. The median time between consent and transplantation of a kidney from an HCV-viremic donor was 6.3 weeks. All 30 recipients achieved a sustained virologic response. One recipient died of complications of sepsis 4 months after achieving a sustained virologic response. No severe adverse events in any patient were deemed likely related to HCV infection or treatment with glecaprevir and pibrentasvir. Three recipients developed acute cellular rejection, which was borderline in one case. Three recipients developed polyomavirus (BK) viremia near or >10,000 copies/ml that resolved after reduction of immunosuppression. All recipients had good allograft function, with a median creatinine of 1.2 mg/dl and median eGFR of 57 ml/min per 1.73 m2 at 6 months.ConclusionsOur multicenter trial demonstrated safety and efficacy of transplantation of 30 HCV-viremic kidneys into HCV-negative recipients, followed by early initiation of an 8-week regimen of glecaprevir and pibrentasvir.

Pan-Genotype Pre-Exposure Prophylaxis (PrEP) Allows Transplantation of HCV-Positive Donor Kidneys to Negative Transplant Recipients

“…We started PrEP DAA shortly before the transplant procedure to avoid logistic challenges of pre-transplant HCV RNA determination to utilize HCV+ donors promptly. Other larger studies show excellent results with the pan-genotypic treatment regimen glecaprevir and pibrentasvir over eight [ 15 ] or only four weeks [ 16 ].…”

Updated View on Kidney Transplant from HCV-Infected Donors and DAAs

“…Regimens provided with safety and efficacy towards all HCV genotypes, even in patients with advanced CKD, should be adopted. Overall, a total of 201 kidney transplants were collected ( Table 3 ); as listed in Table 3 and Table 4 , the majority of the reports had high efficacy and safety [ 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ]. However, some studies were externally funded, and this is a source of bias [ 48 ].…”

“…Nonetheless, pre-emptive and prophylactic approaches are two strategies that are not easily reproducible in the “real-world” where access to DAAs can be biased by barriers such as insurance approval. Many studies reported in Table 3 and Table 4 received funding [ 38 , 39 , 40 , 42 , 43 , 47 ] and did not generate “real-world” evidence. It is difficult to understand whether some AEs were related to the transmission of HCV infection, use of DAAs, or kidney transplant per se.…”

It is not only extending donor criteria: it is extending the donor pool. A cross‐sectional survey from the European Society of Organ Transplantation

“…In summary, many transplant professionals were willing to accept donors with an additional risk of transmission of infectious or malignant disease although there was no consensus on clinical pathways [1][2][3]. Many centres closed during the height of the pandemic and now have continuation plans in place [4][5][6].…”