Merck Sharp & Dohme Corp.

Recurrent hepatitis C virus (HCV) infection after liver transplantation (LT) is associated with accelerated progression of liver disease, frequently leading to graft loss and early death. Existing treatment options for severe recurrent HCV infection are limited by suboptimal efficacy, poor tolerability, and numerous drug interactions. We provided sofosbuvir (SOF) and ribavirin (RBV) on a compassionate-use basis to patients with severe recurrent hepatitis C, including those with fibrosing cholestatic hepatitis (FCH) and decompensated cirrhosis who had a life expectancy of 1 year or less. All patients were to receive 24-48 weeks of SOF plus RBV. Investigators could add pegylated interferon to the regimen at their discretion. Data from the first 104 patients who completed or prematurely discontinued treatment by January 1, 2014 are presented. Of the 104 patients analyzed, 52 had an early severe recurrence (diagnosed <12 months after LT) and 52 had cirrhosis (diagnosed >12 months after LT). Twelve patients who underwent retransplantation were excluded from our efficacy analysis. Of the 92 patients assessed, 54 (59%) achieved sustained virological response (SVR) at 12 weeks after the end of treatment, with a higher rate (73%; 35 of 48) in patients with early severe recurrence. Of the 103 patients assessed for clinical outcome, 59 (57%) reported clinical improvement at the last study visit, 23 (22%) were unchanged, 3 (3%) had a worsened clinical status, and 13 (13%) died. Overall, 123 serious adverse events (SAEs) occurred in 49 patients (47%). SAEs associated with hepatic decompensation were the most frequent, with 26 SAEs occurring in 19 patients (18%). Conclusion: SOF and RBV provide high rates of SVR in patients with severe recurrent HCV, including patients with early severe recurrence, FCH, and cirrhosis. (HEPATOLOGY 2015;61:1485-1494