Recurrent hepatitis C after liver transplantation: A nonrandomized trial of interferon alfa alone versus interferon alfa and ribavirin

Liver transplant recipients with recurrent hepatitis C virus (HCV) infectio n often have histological hepatitis, and in some patients, graft failure de velops. The aim of this nonrandomized study is to determine the efficacy an d tolerability of interferon alfa (IFN alfa) alone and IFN alfa and ribavir in combination therapy in such patients. Forty transplant recipients with r ecurrent hepatitis were initiated on therapy with IFN alfa-2b at 3 million units (MU) three times weekly for 1 month followed by 5 MU three times week ly for 5 months. Twenty patients were administered IFN alfa-2b, 3 MU three times weekly for 1 month followed by 5 MU three times weekly for 11 months, and ribavirin, 600 mg, twice daily orally for 12 months concurrently. The primary end point was sustained clearance of serum HCV RNA, and secondary e nd points were serum alanine aminotransferase (ALT) level normalization and histological improvement. Thirty patients completed 6 months of IFN-alfa m onotherapy and 15 patients completed 12 months of IFN alfa and ribavirin co mbination therapy. End-of-treatment biochemical responses were similar in t he two groups (IFN alfa, 20% v combination therapy, 25%); however, viral cl earance was greater in the combination-therapy group (40% v 15%; P = .04). Six months after the completion of therapy, only 1 patient (2.5%) in the IF N-alfa group and 4 patients (20%) in the combination-therapy group were HCV RNA negative (P = .03). Serum ALT and HCV RNA levels declined significantl y in both groups during therapy. There was no improvement in inflammatory g rade, and fibrosis score was worse in both groups. Ten patients (25%) in th e IFN-alfa group and 5 patients (20%) in the combination-therapy group with drew because of adverse effects. We conclude that in liver allograft recipi ents with recurrent hepatitis C, combination therapy with IFN alfa and riba virin is more efficacious than treatment with IFN alfa alone. However, the efficacy is limited by tolerability.