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
Authors: Sise Meghan E. , Goldberg David S. , Kort Jens J. , Schaubel Douglas E. , Alloway Rita R. , Durand Christine M. , Fontana Robert J. , Brown Robert S. , Friedewald John J. , Prenner Stacey , Landis J. Richard , Fernando Melissa , Phillips Caitlin C. , Woodle E. Steve , Rike-Shields Adele , Sherman Kenneth E. , Elias Nahel , Williams Winfred W. , Gustafson Jenna L. , Desai Niraj M. , Barnaba Brittany , Norman Silas P. , Doshi Mona , Sultan Samuel T. , Aull Meredith J. , Levitsky Josh , Belshe Dianne S. , Chung Raymond T. , Reese Peter P. 
Published: August 2020

Significance Statement
Single-center trials and retrospective case series have reported promising outcomes transplanting kidneys from donors with hepatitis C virus (HCV) infection into HCV-negative recipients, although concerns remain about immunologic complications. In this first multicenter trial, 30 HCV-uninfected adults received a kidney from an HCV-viremic deceased donor and were cured of HCV with an 8-week regimen of coformulated glecaprevir and pibrentasvir initiated 2–5 days post-transplant. Three patients developed acute cellular rejection and three developed BK viremia near or >10,000 copies/ml that resolved after immunosupression reduction; none experienced severe adverse events associated with the antiviral treatment or HCV. Overall allograft function at 6 months was excellent. These findings demonstrate that HCV-viremic kidneys offer a valuable resource for transplantation and that donor-derived HCV can be effectively managed with early antiviral treatment.

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.