Recurrence of hepatitis C virus (HCV) infection is inevitable in viremic patients undergoing liver transplantation (LT).1, 2 Aggressive recurrence of hepatitis C is associated with rapid progression to cirrhosis, graft failure, and death or need for LT.3-5 Prevention of allograft reinfection by pretransplant antiviral therapy is one strategy for improving graft and patient outcomes in recipients transplanted for chronic hepatitis C (CHC).
Virologic response to pegylated interferon (Peg-IFN) and ribavirin (RBV) is reduced in cirrhosis. In the registration trials for Peg-IFN/RBV, the rates of sustained virologic response (SVR) were 5%-15% lower in patients with advanced fibrosis or cirrhosis.6-8 Likelihood of SVR further diminishes with increasing severity of liver disease as the result of poor tolerability, dose reductions, discontinuation of therapy, and intrinsically compromised response to Peg-IFN/RBV.9-11 SVR was only demonstrated in 13% of patients with HCV genotype 1 and decompensated liver disease, two thirds of whom were treatment naïve.12
Despite the reduced rates of SVR among patients with advanced liver disease, on-treatment clearance of HCV ribonucleic acid (RNA) from blood can be achieved in 30%-40% of patients with HCV genotype 1 and 70%-90% of patients with HCV genotypes 2 or 3. In the setting of LT, rendering blood free of HCV RNA before transplantation could potentially limit the risk for recurrent HCV after LT. Five published reports have suggested that suppression of HCV RNA in patients with advanced disease is achievable, and that 20%-30% of treated patients may remain free of HCV infection after transplantation.12-16 None of these reports was a randomized trial, limiting conclusions regarding efficacy and, more important, safety.
Herein, we report the efficacy and safety of Peg-IFN/RBV to prevent the recurrence of HCV in a cohort of patients from the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL).