Lung Transplantation Using Hepatitis C Viremic Donors: An Open-Label Single Center Pilot Trial of Prevention of Viral Transmission

Abstract

Background: A significant proportion of organ donors currently test positive for hepatitis C virus (HCV) infection. To date, only a few studies have evaluated the safety of using lungs from these donors for transplantation, and no direct interventions to donor organs have been performed with the aim of preventing HCV transmission via organ transplantation. Methods: We performed a single center prospective non-randomized trial where donor lungs from HCV viremic donors were transplanted into HCV negative (HCV-ve) recipients. Outcomes of study recipients were compared to patients receiving HCV-ve donors. Primary endpoints were survival and HCV status at 6 months after transplantation. Prior to implantation, all donor lungs were treated with ex vivo lung perfusion (EVLP) with (n=11) or without (n=11) ultraviolet C (UVC) perfusate irradiation to reduce HCV RNA levels and infectivity. All patients becoming viremic received 12 weeks of sofosbuvir/velpatasvir (S/V) starting at least 2 weeks after transplantation. Findings: During the 13-month study period, 22 patients were transplanted using viremic HCV donors and 187 with HCV-ve donors. Recipient age, lung disease, urgency status and positive donor-recipient HLA crossmatch were similar between the 2 groups. Post-transplant outcomes such as primary graft dysfunction grades, ICU and hospital length of stay, and survival were similar between the 2 groups. Twenty patients (91%) developed HCV viremia within the first week after transplantation and underwent S/V treatment starting at a median of 21 days after transplantation (range 14-71 days). Donor organ treatment with EVLP+UVC was associated with significantly lower recipient viral loads in blood within the first week after transplantation, and prevention of transmission in 2/11 patients. All infected patients achieved negative HCV PCR within 6 weeks of treatment initiation. Two patients presented with HCV relapse within 3 months after S/V completion requiring retreatment. Interpretation: Early and intermediate-term clinical outcomes using viremic HCV donors were similar to patients receiving HCV-ve donor lungs. Donor organ treatment using UVC perfusate irradiation during EVLP showed a significant impact in decreasing HCV viral loads within the first 7 days after transplantation. Trial Registration Number: The trial was registered at clinicaltrials.gov (NCT03112044). Funding Statement: This study was an investigator-initiated study funded by an operating grant from the Canadian Institutes of Health Research (CIHR). Gilead Sciences provided S/V (Epclusa) for all patients in the study. XVIVO perfusion (Gothenburg, Sweden) provided Steen solution for EVLP Declaration of Interests: Dr. Cypel, Waddell and Keshavjee are co-founders of Perfusix Canada, XOR Labs Toronto, and consultants for Lung Bioengineering (United Therapeutics). Ethics Approval Statement: This study was approved by the Research Ethics Board of University Health Network and subjects provided written informed consent while on the transplant waiting list prior to the offer of HCV+ve donor lungs.