Boceprevir Treatment in Liver Pre-transplant HCV Patients

End-stage liver disease due to hepatitis C virus (HCV) is the most common indication for liver transplantation(LT) worldwide (30\~40%). Within 5 years, about 25-30% of liver transplant recipients with recurrent hepatitis C would progress to liver cirrhosis (Ponziani et. Al, 2011), it also accounts for 2/3 of graft failure and deaths after liver transplantation.(Bzowej et al., 2011)

Kaohsiung Chang Gung Memorial Hospital continue to have at least 45 HCV-related liver disease patients awaiting for liver transplantation annually. If the HCV viral load can be significantly reduced or sustained virologic response (SVR) can be achieved by triple therapy with pegylated interferon alfa (PEG)/Ribavirin(RBV)/Boceprevir(BOC) treatment before liver transplantation(LT), the graft re-infection of HCV can be prevented. By this way, we can reduce the risk of early fibrosis progression in the liver graft, and hopefully, improving graft and patient survival after liver transplantation.(Toniutto, 2008)(Ponziani et al, 2011).

We aim to conduct a prospective, open label, single arm study. This study design is single arm to treat HCV patients with pegylated interferon alfa (PEG)/Ribavirin(RBV)/Boceprevir(BOC) triple therapies before liver transplantation for patients with detectable HCV RNA. The total number of patients would be around 20 cases included in the study and all of them will take pegylated interferon alfa (PEG)/Ribavirin(RBV)/Boceprevir(BOC) triple therapy. The experimental regimen contains 4 week lead-in therapy with Peg-Interferon α-2b plus Ribavirin, followed by Boceprevir + Peg-Interferon α-2b + Ribavirin for at least 16 weeks or maximal 44 weeks before transplantation. The treatment will be discontinued immediately at time of liver transplantation. Normal practice based on the treatment protocol of the Kaohsiung Chang Gung Memorial Hospital liver transplant center will be done before enrollment.

-Treatment Stopping Rules-

If the patient has HCV RNA >100 IU/ml at week 12 after the beginning of treatment with peg interferon plus ribavirin, i.e. 8 weeks after the initiation of therapy with boceprevir, all HCV medications are to be discontinued.

If the patient has detectable HCV RNA at Week 24 after the beginning of treatment with peg interferon plus ribavirin, i.e. 20 weeks after the initiation of therapy with boceprevir, all HCV medications are to be discontinued.

Monitoring of Patients during Treatment Complete blood counts should be obtained pretreatment, Treatment Week 4, Treatment Week 8, and thereafter, as clinically appropriate. If serum hemoglobin is \<10 g/dL, a decrease in dosage of ribavirin and/or administration with erythropoietin (epoetin alfa) may be warranted.

-Primary Outcome Measure: Title: Number of Participants with Adverse Events as a Measure of Safety Time Frame: Up to the time of liver transplant

-Secondary Outcome Measures: Title: HCV-RNA (Hepatitis C virus RNA) level Time Frame: Baseline, Treatment Week 12 , Treatment Week 24. A follow-up test is recommended 24 weeks after the completion of treatment, or at time of liver transplant. Finally, patients will receive regular monitoring of HCV RNA 1, 3, 6, 9, 12 months after liver transplantation.