A US multicenter study of hepatitis C treatment of liver transplant recipients with protease-inhibitor triple therapy.

Background & Aims: NS3/4A protease inhibitors, boceprevir or telaprevir, combined with peginterferon and ribavirin was the standard treatment for HCV genotype 1 and remains the only available direct antiviral drug based therapy in some countries. Efficacy and safety data in liver transplant recipients are limited.

Methods: This was a retrospective cohort study of 81 patients with genotype 1 HCV treated with boceprevir (10%) or telaprevir (90%) plus peginterferon and ribavirin at 6 US transplant centers (53% stage 3-4/4 fibrosis, 57% treatment experienced). The primary end point was undetectable HCV RNA 12 weeks after treatment completion (SVR12).

Results: The intent-to-treat SVR12 rate was 63% (51/81). Patients with an extended rapid virologic response, (undetectable HCV RNA at 4 and 12 weeks after starting boceprevir or telaprevir), had a higher rate of SVR12 than all other patients (85% vs. 15%, p<0.001). Adverse effects were common; 21% of patients experienced hemoglobin <8g/dl and 57% required blood transfusions during the first 16 weeks. Twenty seven percent were hospitalized and 9% died; all were liver-related.

Conclusions: The addition of boceprevir or telaprevir to peginterferon and ribavirin yields SVR12 of 63% in liver transplant recipients with genotype 1 recurrent HCV, despite a high prevalence of advanced fibrosis and prior non-response to peginterferon and ribavirin. Rapid virologic response predicted a high likelihood of SVR. Despite a doubling of SVR rates, poor tolerability and high rates of adverse events were frequent and pose barriers to its widespread application.