*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.
To evaluate the safety and efficacy of peginterferon-α-2b plus ribavirin in patients with recurrent hepatitis C after orthotopic liver transplant.
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.
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).
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%).
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.