Preemptive Pan-Genotypic Direct Acting Antiviral Therapy in Donor HCV-Positive to Recipient HCV-Negative Cardiac Transplantation Produces Viral Clearance and is Associated with Favorable Outcomes

Abstract

Summary of Objectives Limited donor heart availability highlights the importance of identifying all potentially transplantable organs. We sought to determine if preemptive administration of pan-genotypic direct-acting antiviral therapy could prevent the development of chronic hepatitis C virus (HCV) infection while expediting access to donor hearts. Methods We developed a novel non-industry funded protocol supporting HCV donor-positive to recipient-negative heart transplantation (HT). In this single center proof-of-concept trial, patients receiving a NAT-positive HT received preemptive oral glecaprevir-pibrentasvir (GP) on call to the operating room followed by an 8-week course of GP post-transplant. Patient's receiving HCV-antibody positive donors without detectable circulating HCV by nucleic acid testing (NAT) were followed with a reactive approach, and started on GP therapy only if they developed viremia. HCV RNA monitoring was performed to ensure viral suppression and sustained virologic response (SVR). Endpoints Between Nov 2017 and Oct 2018, 23 patients underwent HT with HCV-positive donor hearts, 3 of whom underwent simultaneous heart-kidney transplantation. Median pre-transplant waiting time for patients following enrollment in the HCV protocol (20, IQR 5-59 days) has been lower than that for the 99 patients who have undergone HT outside of the HCV protocol in the last 3 years (113, IQR 40-366 days, p=0.0001). Average peak recipient HCV viral loads were