Prevention of viral transmission during lung transplantation with hepatitis C-viraemic donors: an open-label, single-centre, pilot trial

A substantial proportion of organ donors 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 done with the aim of preventing HCV transmission via organ transplantation. We aimed to assess the safety and efficacy of lung transplantation in humans from HCV-positive donors to HCV-negative recipients after application of ex-vivo lung perfusion (EVLP) plus ultraviolet C (UVC) perfusate irradiation. We did a single centre, prospective, open-label, non-randomised trial in which donor lungs from HCV-viraemic donors (HCV-positive) were transplanted into HCV-negative recipients at Toronto General Hospital, University Health Network (Toronto, ON, Canada). Donors were younger than 65 years old and tested positive for HCV by nucleic acid testing. Donors who tested positive for hepatitis B virus, HIV, human T-lymphotropic virus 1 or 2 were excluded. Recipients were on the lung transplant waiting list without significant liver disease (stage 2 fibrosis or higher were excluded) or active HCV infection. Before implantation, all HCV-positive donor lungs were treated with EVLP with or without UVC perfusate irradiation to reduce the concentration of HCV RNA and infectivity. For the first week after transplantation, patients' HCV RNA blood concentrations were measured once daily, then once per week for 12 weeks. All patients received 12 weeks of oral sofosbuvir 400 mg plus velpatasvir 100 mg, starting at least 2 weeks after transplantation. The primary endpoint was a composite of survival and HCV-free status at 6 months after transplantation in all patients who received HCV-positive lungs. Patient outcomes such as survival, time in hospital, and incidence of acute rejection were compared between those receiving HCV-positive lungs and all patients who received HCV-negative lung transplants during the study period. The study is registered with ClinicalTrials.gov, NCT03112044. From Oct 1, 2017, to Nov 1, 2018, 209 patients had a transplantation; of 27 donors who were HCV-positive and initially considered, 22 were suitable for transplantation. The remaining 187 donors were HCV-negative. Before implantation, 11 of the HCV-positive donor lungs were treated with EVLP alone and the other 11 were treated with EVLP plus UVC. Lung disease, urgency status, and positive donor-recipient HLA crossmatch were similar between the pati