1Beth Israel Deaconess Medical Center, Boston, MA. Electronic address: email@example.com.
2Liver Unit, Hospital Clínic, IDIBAPS and CIBEREHD, Barcelona, Spain.
3Massachusetts General Hospital, Boston, MA.
4University of California San Francisco, San Francisco, CA.
5Columbia University, New York, NY.
6Thomas Jefferson University Hospital, Philadelphia, PA.
7Lahey Clinic, Burlington, MA.
8Baylor University Medical Center, Dallas, TX.
9University of California, San Diego, La Jolla, CA.
10Mount Sinai School of Medicine, New York, NY.
11University of Colorado, Denver, CO.
12University of Miami, Miami, FL.
13Saint Louis University, St. Louis, MO.
14Auckland City Hospital, Auckland, New Zealand.
15University of California, Los Angeles, CA.
16Gilead Sciences, Foster City, CA.
17Henry Ford Health System, Detroit, MI.
18Beth Israel Deaconess Medical Center, Boston, MA.
BACKGROUND AND AIMS:
Patients with detectable hepatitis C virus (HCV) RNA at the time of liver transplantation universally experience recurrent HCV infection. Antiviral treatment before transplantation can prevent HCV recurrence, but existing interferon-based regimens are poorly tolerated and are either ineffective or contraindicated in most patients. We performed a trial to determine whether sofosbuvir and ribavirin treatment before liver transplantation could prevent HCV recurrence afterward.
In a phase 2, open-label study, 61 patients with HCV of any genotype and cirrhosis (Child-Turcotte-Pugh scores ≤7) who were on waitlists for liver transplantation for hepatocellular carcinoma received up to 48 weeks of sofosbuvir (400 mg) and ribavirin before liver transplantation. The primary endpoint was the proportion of patients with levels of HCV RNA <25 IU/mL 12 weeks after transplantation among patients with this level of HCV RNA at their last measurement before transplantation.
Sixty-one patients received sofosbuvir and ribavirin, and 46 received transplanted livers. The per protocol efficacy population consisted of 43 patients who had HCV RNA <25 IU/mL at the time of transplantation. Of these 43 patients, 30 (70%) had pTVR12, 10 (23%) had recurrent infection, and 3 (7%) died (2 from non-function of the primary graft and 1 from complications of hepatic artery thrombosis). Of all 61 patients given sofosbuvir and ribavirin, 49% had a pTVR. Recurrence was inversely related to the number of consecutive days of undetectable HCV RNA before transplantation. The most frequently reported adverse events were fatigue (in 38% of patients), headache (23%), and anemia (21%).
Administration of sofosbuvir and ribavirin before liver transplantation can prevent post-transplant HCV recurrence. Trial registration details: NCT01559844 (ClinicalTrials.gov).