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Background. The efficacy of combination therapy with pegylated interferon and ribavirin for recurrent hepatitis C genotype 1 after liver transplantation is limited. In this study, we designed an individualized treatment regimen with pegylated interferon and ribavirin for recurrent hepatitis C based on individual viral responses. Methods. Thirty-four patients with recurrent hepatitis C genotype 1b after living-donor liver transplantation received combination therapy with pegylated interferon α-2b and ribavirin. Treatment was continued for an additional 12 months after serum hepatitis C virus (HCV) RNA became undetectable. Results. Of the 34 patients, 18 became negative for serum HCV RNA within 12 months (range, 1.2-9.9 months; median, 4.0 months). The treatment for the 18 patients was individualized by adding a further 12 months of treatment after the disappearance of serum HCV RNA, resulting in treatment durations of 13.2 to 21.9 months (median, 16.0 months). Notably, 17 (94%) of the 18 patients who received the individualized extended treatment achieved sustained virologic response (SVR), resulting in a 50% SVR rate. Six patients (18%) discontinued the treatment, but none of the 18 patients who received the extended protocol withdrew from the study. Conclusions. Individualized extension of combination therapy with pegylated interferon and ribavirin for recurrent hepatitis C after liver transplantation resulted in a high SVR rate and good tolerability.

Background Effective management of patients with recurrent hepatitis C after liver transplantation has not been established. In this study, we tested the significance of biochemical response (BR) as well as sustained virological response (SVR) to combination therapy with interferon alpha-2b and ribavirin for recurrent hepatitis C after living-donor liver transplantation. Methods Forty patients received therapy and formed 3 groups by response: SVR (n=14, 35%) and BR (n=14, 35%), defined when serum alanine aminotransferase normalized during therapy in non-SVR patients, and no response (NR; n=12, 30%). Histological changes of these groups after the combination therapy were investigated. Results Activity grade of liver histology improved significantly in patients with an SVR at 1 and at 2-4 years after the initiation of treatment, showing difference from the BR and NR groups in which the activity was not improved by interferon therapy. Fibrosis deteriorated significantly in both the BR and the NR groups at two to four years. The rates of patients whose fibrosis stage deteriorated to stage F2 or more were significantly greater in the BR and NR groups than in the SVR group. Fibrosis decreased or remained stable in five of eight patients (63%) with an SVR at two to four years, whereas it increased in 12 of 15 patients (80%) with a BR or NR. Conclusions Patients with an SVR showed histological improvement, but the benefit of a BR for non-SVR patients to improve the activity grade or to inhibit the progression of fibrosis was limited.

Recurrence of hepatitis C after liver transplantation is a major problem; it is characterized by high hepatitis C virus (HCV)-RNA, rapid progression, and cholestatic hepatitis. Treatment for HCV infection with peginterferon and ribavirin has been administered to prevent progression of hepatitis C after liver transplantation. However, it has low efficacy and causes many adverse events, including immune-mediated graft dysfunction. Interferon-containing regimens with direct-acting antivirals (DAAs) improve treatment efficacy but DAAs cause serious adverse events and drug-drug interactions. Recent studies have demonstrated the efficacy and safety of interferon-free therapy with DAAs before and after liver transplantation, which has ushered in a new era in the strategy for treating HCV in transplant recipients. Interferon-free therapies are safe and effective in patients before and after liver transplantation as well as in those with severe cholestatic hepatitis C. Several obstacles must be overcome before the widespread adoption of interferon-free therapy, including drug-drug interactions, DAA-resistant HCV, treatment for decompensated cirrhosis, and treatment for renal failure. These problems are expected to be solved in the near future, and the poor prognosis of HCV-positive recipients will improve.

BACKGROUND Chronic rejection (CR) has been reported to be associated with antiviral therapy for recurrent hepatitis C in liver transplant (LT) recipients. The aims of this study were to clarify the details of antiviral therapy-associated CR after living-donor liver transplantation (LDLT) and to identify the factors associated with CR. METHODS A retrospective chart review was performed on 125 recipients who had received antiviral therapy for recurrent hepatitis C after LDLT between January 2001 and September 2012. The characteristics of patients who developed CR during or within 6 months after antiviral therapy were compared with those of 76 patients who did not develop CR despite receiving antiviral therapy for more than 1 year. RESULTS Seven of 125 (6%) patients developed CR during or within 6 months after the end of antiviral therapy. CR was diagnosed after a median (range) of 9 (1-16) months of antiviral therapy. In five patients, rejection progressed rapidly and resulted in death within 3 months after diagnosis. Analysis revealed two significant factors associated with CR: reduction of the immunosuppressant dose during antiviral therapy and a low fibrosis score as the indication for antiviral therapy. CONCLUSIONS CR developed in association with antiviral therapy for recurrent hepatitis C after LDLT. This complication may be prevented by ensuring that the immunosuppressant dose is not reduced during antiviral therapy.