1Mayo Clinic, Rochester, MN. Electronic address: email@example.com.
2Auckland City Hospital, Auckland, New Zealand.
3Hannover Medical School, Hannover, Germany.
4Columbia University, New York, NY;
5Beth Israel Deaconess Medical Center, Boston, MA.
6Indiana School of Medicine, Indianapolis, IN.
7University of Michigan, Ann Arbor, MI.
8Kansas University Medical Center, Kansas City, KS.
9NYU Medical Center, New York, NY.
10Duke University Medical Center, Durham, NC.
11Gilead Sciences, Foster City, CA.
12AP-HP Hôpital Paul Brousse, Centre Hépatobiliaire, and Université Paris Sud, Villejuif, France.
13Liver Unit, Hospital Clinic, IDIBAPS and CIBEREHD, Barcelona, Spain.
14University of California at San Francisco, San Francisco, CA.
BACKGROUND & AIMS:
Interferon alfa-based regimens used to treat recurrent hepatitis C virus (HCV) infection after liver transplantation are poorly tolerated, associated with generally modest efficacy, and can interact with immunosuppressive agents. We evaluated the efficacy and safety of an interferon-free regimen of the nucleotide polymerase inhibitor sofosbuvir combined with ribavirin for 24 weeks in treating post-transplant HCV infection.
In a prospective, multicenter, open-label pilot study, we enrolled patients with compensated recurrent HCV infection of any genotype after a primary or secondary liver transplant. All patients received 24 weeks of sofosbuvir 400 mg daily and ribavirin starting at 400 mg daily, which was adjusted according to creatinine clearance and hemoglobin values. The primary endpoint was sustained virologic response 12 weeks after treatment (SVR12).
Of the 40 patients enrolled and treated, 78% were male, 85% were white, 83% had HCV genotype 1, 40% had cirrhosis (based on biopsy), and 88% had been previously treated with interferon. SVR12 was achieved by 28/40 patients (70%; 90% confidence interval, 56%-82%). Relapse accounted for all cases of virologic failure. No patients had detectable viral resistance during or after treatment. The most common adverse events were fatigue (30%), diarrhea (28%), and headache (25%). In addition, 20% of the subjects experienced anemia. Two patients discontinued study treatment because of adverse events, which were considered unrelated to study treatment. No deaths, graft losses, or episodes of rejection occurred. No interactions with any concomitant immunosuppressive agents were reported.
Sofosbuvir and ribavirin combination therapy for 24 weeks is an effective and well tolerated interferon-free treatment for post-transplant HCV infection. ClinicalTrials.gov number: NCT01687270.