Treatment of hepatitis C in liver transplant recipients

Recurrent hepatitis C after liver transplantation is a universal phenomenon. Graft reinfection occurs rapidly; once it is established, allograft cirrhosis and decompensation rapidly ensue in many patients. Treatment with pegylated interferon plus ribavirin is the standard of care among nontransplant patients with hepatitis C; however, the applicability of these therapies in liver transplant patients is severely limited. Before transplantation, many patients are simply too ill to endure the long treatment duration necessary to achieve viral eradication; thus, treatment-related toxicity is a frequent barrier to success. Clinical trials in the pretransplantation population have yielded poor outcomes, with sustained virologic response rates only as high as 25%. Early after transplantation, treatment may be initiated prophylactically, or it may be initiated therapeutically in patients with evidence of recurrent disease. In small studies, prophylactic therapy has been associated with sustained virologic response rates lower than 20%, whereas in therapeutic intervention studies, sustained virologic response rates have ranged from 20% to 37%. In the setting of therapeutic intervention, preliminary indications suggest that rapid and early virologic response may become important clinical tools enabling the early identification of patients likely to respond to treatment. Two important clinical trials, PHOENIX (Pegasys and Copegus Administered After Liver Transplantation for Hepatitis C) in the prophylactic setting and PROTECT (Pegylated Interferon Alfa-2b and Ribavirin After Orthotopic Liver Transplantation: Efficacy and Safety in Hepatitis C Recurrence Therapy) in the therapeutic setting, are under way and should further advance our understanding of the management of hepatitis C in patients undergoing liver transplantation.