87. Heart and Lung Transplants From HCV-Viremic Donors to Uninfected Patients: Longer-Term Follow-Up

Abstract

BackgroundThe DONATE HCV Trial demonstrated that hearts and lungs can be safely transplanted from HCV-infected donors using a shortened, 4-week, pre-emptive course of direct-acting antivirals (DAA). The 6-month results from that study of 35 patients are encouraging, but longer-term data from a larger cohort are needed to better define the risk–benefit profile.MethodsWe conducted a single-center trial to transplant thoracic organs from HCV viremic donors, irrespective of HCV genotype, to HCV-uninfected adults. Sofosbuvir/velpatasvir, a pan-genotypic DAA, was pre-emptively administered for 4 weeks, beginning within hours of transplant. The primary outcome was a composite of HCV clearance and graft survival at 6 months post-transplant. Secondary outcomes included graft survival and mortality at 12 months and the occurrence of grade 3 or higher adverse events (AEs). This protocol is IRB approved and all participants provided written informed consent (NCT03086044).ResultsBetween March 2017 and March 2019, 57 participants were enrolled: 46 received lung and 11 received heart transplants. The median donor HCV viral load (VL) was 889,817 IU/mL (IQR 212,062–4,641,078). Of the 57 recipients, 53 (93%) had detectable HCV VL immediately after transplant, with median VL of 1,460 IU/mL (IQR 463–6,618). HCV VL became negative by about 2 weeks and subsequently remained undetectable in all participants. Forty-nine of 49 (100%) and 34 of 35 (97%) participants were alive with excellent graft function and an undetectable HCV VL at 6 months and 1-year post-transplant, respectively. No treatment-related serious AEs were identified. Outcomes between transplant recipients from HCV donors vs. non-HCV donors were similar, including the occurrence of renal failure, respiratory failure, and non-HCV infections.ConclusionIn patients who received thoracic organs from HCV viremic donors, a 4-week antiviral treatment course initiated within hours of transplant prevented the establishment of HCV infection. These data demonstrate that thoracic organs from HCV viremic donors can be transplanted safely with excellent graft and recipient survival at 12 months with a similar AE profile compared with transplant recipients who received thoracic organs from non-HCV donors. Two-year outcomes will be available in October 2019.Disclosures All Authors: No reported Disclosures.

Acute hepatitis C virus infection: clinical update and remaining challenges

“…125 Table 5 summarizes the representative trials that used DAA treatment to manage acute HCV infection in HCV-negative patients receiving HCV-viremic solid organs. [126][127][128][129][130][131][132][133][134][135][136][137][138][139][140][141][142] In general, the SVR12 rates were 100% when DAAs were administered for the same duration as indicated for chronic HCV infection. In addition, the SVR12 rate, excluding non-virologic failures, can reach > 94% if the solid organ recipients received prophylactic or pre-emptive DAAs for more than one week.…”

Expanding the Criteria for Heart Transplantation Donors: A Review of DCD, Increased Ischemic Times, HCV, HIV, and Extended Criteria Donors

“…The optimal regimen and timing in transplant patients continues to evolve, especially with the advent of newer generations of DAAs. While DAAs have traditionally been given to recipients who develop viremia after transplantation, studies have shown that prophylactic use of DAA regimens successfully treat viremia without any serious adverse events post-transplant [110][111][112][113]. Timing of DAA administration in HT patients is heavily influenced by insurance approval, which can often require a prior authorization, perhaps eliciting an administrative burden that may be a barrier to use of these organs.…”