Goals: To evaluate the safety and efficacy of peginterferon-α-2b plus ribavirin in patients with recurrent hepatitis C after orthotopic liver transplant.
Background: Reinfection of liver allografts in hepatitis C virus -infected transplant recipients begins immediately after transplantation. Treatment of these patients is challenging because of poor tolerability.
Study: A multicenter, open-label study enrolling patients with persistent viremia after primary orthotopic liver transplant for cirrhosis related to hepatitis C virus infection. Patients received peginterferon-α-2b (1.5 µg/kg/wk) plus ribavirin (400 to 1200 mg/d administered using a dose-escalating regimen and according to body weight) for 48 weeks. The primary endpoint was sustained virologic response (SVR).
Results: In total, 125 patients started treatment and 58.4% completed 48 weeks. SVR rate was 28.8% (G1, 23.8%; G2/3, 55.0%), end-of-treatment response rate was 40.8%, and relapse rate was 18.2%. SVR was 55% among patients who completed treatment. Genotype 2/3 infection, male sex, baseline hemoglobin>14 g/dL, 80:80:80 compliance, rapid virologic response (RVR), and complete early virologic response (cEVR) were predictors of SVR. SVR was higher among patients with RVR compared with those without RVR (83.3% vs. 25.7%; P=0.0098), and among patients with cEVR compared with those without EVR (66.7% vs. 1.8%; P<0.0001). Thirty-eight patients discontinued because of an adverse event and 69 required dose reduction or interruption. Anemia (74%) and neutropenia (30%) were common, and rejection was low (3.2%).
Conclusions: SVR was low in this study. Anemia was a particular challenge in achieving maximal ribavirin therapeutic exposure and may account in part for the lower SVR.
*Department of Transplantation, Tufts Medical School, Lahey Clinic Medical Center, Burlington, MA
†Division of Gastroenterology/Hepatology, Indiana University, Indianapolis, IN
‡Texas Digestive Disease Consultants, Arlington, TX
§Division of Gastroenterology, Washington University, St Louis, MO
∥Division of Hepatology, Mayo Clinic, Scottsdale, AZ
¶Division of Gastroenterology and Hepatology, Henry Ford Hospital, Detroit, MI
#Division of Liver Diseases, The Mount Sinai Medical Center
††Columbia University College of Physicians & Surgeons, New York, NY
**Merck Sharp & Dohme Corp., Whitehouse Station, NJ
In addition to the authors, the participants and members of this study group include the following: Graham Barnard, David Barnes, Paul Hayashi, Alvaro Koch, Laura Kulik, Michael Lucey, Parvez Mantry, Sandeep Mukherjee, Guy Neff, Mojtaba Olyaee, Fred Poordad, Nikolaos Pyrsopolous, Alastair Smith, and Lewis Teperman.
The study discussed in this manuscript was funded by Schering-Plough Corp., now Merck, Sharp & Dohme Corp., Kenilworth, NJ. Medical writing and editorial assistance was provided by Tim Ibbotson, PhD and Santo D’Angelo, PhD, MS, of ApotheCom, PA. This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., Whitehouse Station, NJ.
F.D.G. has served as a consultant and on speakers bureaus for Merck and has also received grant support from Merck. P.K. has served as a consultant for Merck, Vertex, Anadys, Gilead, Bristol-Myers Squibb, Abbott, Boehringer Ingelheim, and Novartis; has received grants from Merck, Vertex, Bristol-Myers Squibb, Gilead, Abbott, Anadys, Conatus, and Roche; and has served on speakers bureaus for Merck, Roche, Bristol-Myers Squibb, and Gilead. R.G. has served on speakers bureaus and delivered lectures for Vertex, Roche, and Merck. J.C. has received grant support Schering-Plough/Merck. H.E.V. has served as a consultant for and also received grant support from Merck. K.A.B. has served as a consultant on advisory boards for Merck, Gilead, Salix, Bayer/Onyx, and Vertex; has received grants from Bristol-Myers Squibb, Gilead, Novartis, Ikaria, Hyperion, CDC Foundation, Bayer/Onyx; and has served on speakers bureaus for Gilead, Merck, Vertex, and Bayer/Onyx. T.S. has served as a consultant for Vertex, Merck, Salix, Gilead; and has received research grant from Mass Biologics. E.C. and L.D.P. are employees of, and hold stock in Merck. R.S.B. has received grant support and served on speakers bureaus for Merck.
Reprints: Fredric D. Gordon, MD, Department of Transplantation, Tufts Medical School, Lahey Clinic Medical Center, 41 Mall Road, Burlington, MA 01805 (e-mail: email@example.com).
Received October 14, 2011
Accepted March 30, 2012