16 and 17 In more than 3000 patients treated to date, sofosbuvir has been shown to be safe, viral breakthrough during treatment has been rare (and associated with nonadherence), and few drug interactions

have been observed.18 and 19 In addition, patients with hepatic impairment do not require modification of sofosbuvir dosage.20 We conducted this open-label study to determine if the administration of up to 48 weeks of sofosbuvir and ribavirin to HCV-infected patients with liver cancer before liver transplantation could prevent post-transplant recurrence of HCV infection. Patients were enrolled at 13 centers in the United States, 1 in New Zealand, and 1 in Spain. Eligible patients were at least 18 years old with a body mass index selleck products of ≥18 kg/m2 and documented HCV infection of any genotype with an HCV-RNA value greater than 104 IU/mL. Patients who had failed previous treatment for HCV were eligible. Patients were required to be on the waiting list for liver transplantation (with anticipated time until transplantation of <1 y) from a deceased donor. Patients had HCC meeting the Milan criteria,21 with a biological model for end-stage liver disease (MELD) score of less Epigenetics inhibitor than 22, and a Child–Turcotte–Pugh score of 7 or less, and had to

be eligible for a MELD exception score as per the policy of the United Network for Organ Sharing. We chose to study patients with HCC because they could be expected to undergo liver transplantation within 1 year. This phase 2, open-label, pilot study had 2 phases: a pretransplant treatment phase and a post-transplant follow-up phase. During the pretransplant treatment phase, patients received sofosbuvir (Gilead Sciences) administered orally

at a dose of 400 mg once daily, along with ribavirin (Ribasphere; Kadmon) administered orally as a divided dose according to body weight (1000 mg/day in patients with a body weight of <75 kg, and 1200 mg/day in patients with a body weight of ≥75 kg). According to the original study protocol, treatment mafosfamide lasted up to 24 weeks or until time of transplant, whichever occurred first. Patients who completed treatment before transplantation also were assessed for sustained virologic response. Patients who relapsed after stopping the study drug during the pretransplant treatment phase and who were not found to have the S282T NS5B mutation (which is associated with resistance to sofosbuvir) were allowed to restart treatment and continue for an additional 24 weeks or until transplant. In a subsequent amendment, the study design was changed to allow all patients who had not reached 24 weeks of treatment at the time of the amendment to continue treatment uninterrupted to 48 weeks or transplant. This change was made after observing virologic relapse in 3 patients before transplantation in patients who stopped treatment after completing 24 weeks.