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

Background: Single-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.

Methods: We 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.

Results: We 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.

Conclusions: Our 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.

Keywords: direct-acting antivirals; hepatitis C virus; kidney transplantation; organ allocation.

Copyright © 2020 by the American Society of Nephrology.

Figures

Graphical abstract

Figure 1.

Consort diagram. The seven usual care transplants (six deceased donor and one living donor) involved donors that did not meet inclusion/exclusion donor criteria for MYTHIC.

Figure 2.

Change in log10 HCV viral load for 30 HCV-negative recipients of HCV-viremic kidneys. Detectable but unquantifiable HCV RNA is shown as 14 IU/ml as the lower limit of quantification for some assays was 15 IU/ml. Treatment with glecaprevir/pibrentasvir lasted 8 weeks. HCV, hepatitis C virus.

Figure 3.

Post-transplant trends in serum creatinine in 30 HCV-negative recipients of HCV-viremic kidneys.

Figure 4.

Post-transplant trends in serum ALT in 30 HCV-negative recipients of HCV-viremic kidneys. Glecaprevir/pibrentasvir (G/P) was started between days 2–5 in arm one recipients. Per protocol, ALT was measured peri-transplant, and at the following visits after transplant: day 3, day 1 of G/P treatment, week 1 treatment, week 4 treatment, and week 8 treatment.