1Columbia University, New York, NY.
2Baylor University Medical Center, Dallas, TX.
3University of Pennsylvania, Philadelphia, PA.
4University of California, San Diego, San Diego, CA.
5University of Florida, Gainesville, FL.
6University of Colorado Denver, Aurora, CO.
7Virginia Commonwealth University, Richmond, VA.
8Johns Hopkins University, Baltimore, MD.
9Saint Louis University, Saint Louis, MO.
10Indiana University, Indianapolis, IN.
11Scripps Clinic, La Jolla, CA.
12University of North Carolina, Chapel Hill, North Carolina.
13University of California, San Francisco, San Francisco, CA.
Recurrent infection with the hepatitis C virus (HCV) after liver transplantation is associated with decreased graft and patient survival. Achieving sustained virological response (SVR) with antiviral therapy improves survival. Because interferon-based therapy has limited efficacy and is poorly tolerated, there has been rapid transition to interferon-free direct-acting antiviral (DAA) regimens. Herein the experience with DAAs in the treatment of post-transplant genotype 1HCV from a consortium of community and academic centers (HCV TARGET) is described.
Twenty-one of the 54 centers contributing to the HCV TARGET consortium participated in this study. Enrollment criteria included positive post-transplant HCV RNA prior to treatment, HCV genotype 1, and documentation of use of a simeprevir/sofosbuvir (SMV/SOF) containing DAA regimen. Safety and efficacy were assessed. SVR was defined as undetectable HCV RNA 64 days or later after cessation of treatment.
A total of 162 patients enrolled in HCV-TARGET started treatment with SMV/SOF with or without ribavirin following liver transplantation. The study population included 151 patients treated with these regimens for whom outcomes and safety data were available. The majority of the 151 patients were treated with sofosbuvir and simeprevir alone (n=119, 78%) or with ribavirin (n=32, 22%), The duration of therapy was 12 weeks for most patients, although 15 patients received 24 weeks of treatment. Of all patients receiving SOF/SIM +/- Ribavirin, 133/151 (88%) achieved SVR12 and 11 relapsed (7%). One patient had virologic breakthrough (n=1) and 6 patients were lost to post treatment follow up. Serious adverse events occurred in 12%; 3 patients (all cirrhotic) died due to aspiration pneumonia, suicide, and multi-organ failure. One experienced liver transplant rejection.
Interferon-free DAA treatment represents a major improvement over prior interferon-based therapy. Broader application of these and other emerging DAA regimens in the treatment of post-transplant hepatitis C is warranted.