Daily interferon therapy for hepatitis C virus infection in liver transplant recipients

Background. Hepatitis C virus infection persists after liver transplantatio n and causes recurrent Liver injury in the majority of patients. Standard d ose interferon therapy has been largely unsuccessful for hepatitis C in tra nsplant recipients. Methods. 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-alpha2 alpha, 3 mU daily for 12 months (n=8) or no treatment (n=4), The tolerability of daily interferon dosing in live r transplant recipients was evaluated and effects on hepatitis C virus RNA level, quasispecies evolution, and liver histology were studied. Results. Treated patients had an improvement in histological activity index at the end of therapy relative to controls (median reduction of 2 versus m edian increase of 1.5) (P=0.04). Four treated patients had a virological re sponse (all bDNA negative, one qualitative polymerase chain reaction negati ve) compared with none of the untreated patients. Only two of six treated p atients tested had evidence of quasispecies diversification on therapy. Sev en of eight patients in the treatment group required dose reduction for fat igue and/or depression. They tolerated 1.5 mU of interferon-alpha2 alpha da ily. Two treated patients developed graft dysfunction, one of who had histo logical evidence of rejection and subsequent graft loss. Conclusions. Low daily doses of interferon were tolerated by liver transpla nt recipients and provided histological benefit without associated quasispe cies diversification in most cases. These findings provide a rationale to s tudy low dose daily or pegylated interferon maintenance therapy for the man agement of hepatitis C posttransplant.