DAILY INTERFERON THERAPY FOR HEPATITIS C VIRUS INFECTION IN LIVER TRANSPLANT RECIPIENTS

Abstract

Hepatitis C virus infection persists after liver transplantation and causes recurrent liver injury in the majority of patients. Standard dose interferon therapy has been largely unsuccessful for hepatitis C in transplant recipients. Twelve patients, at least 7 months posttransplant, with detectable hepatitis C virus RNA in serum and features of hepatitis C on liver biopsy were randomized to interferon-α2a, 3 mU daily for 12 months (n=8) or no treatment (n=4). The tolerability of daily interferon dosing in liver transplant recipients was evaluated and effects on hepatitis C virus RNA level, quasispecies evolution, and liver histology were studied. Treated patients had an improvement in histological activity index at the end of therapy relative to controls (median reduction of 2 versus median increase of 1.5) (P =0.04). Four treated patients had a virological response (all bDNA negative, one qualitative polymerase chain reaction negative) compared with none of the untreated patients. Only two of six treated patients tested had evidence of quasispecies diversification on therapy. Seven of eight patients in the treatment group required dose reduction for fatigue and/or depression. They tolerated 1.5 mU of interferon-α2a daily. Two treated patients developed graft dysfunction, one of who had histological evidence of rejection and subsequent graft loss. Low daily doses of interferon were tolerated by liver transplant recipients and provided histological benefit without associated quasispecies diversification in most cases. These findings provide a rationale to study low dose daily or pegylated interferon maintenance therapy for the management of hepatitis C posttransplant.