Source

University Hospital Tuebingen, Medical Clinic, Department of Gastroenterology, Hepatology, and Infectiology, Tuebingen, Germany.

Abstract

Following liver transplantation, management of recurrent Hepatitis C virus (HCV) infection still remains a major challenge. In non-transplanted HCV genotype 1 patients the introduction of protease inhibitor based regimens has increased the rate of sustained virological response, significantly. This pilot study investigated both safety and efficacy data of a telaprevir-based triple therapy in liver transplant HCV patients with special emphasis on drug-drug interactions between immunosuppressants and protease inhibitors. Gathering week 12 safety and efficacy data in 9 liver transplant HCV patients who have been treated with a combination of telaprevir, pegylated interferon, and ribavirin, in parallel with immunosuppressive drugs such as tacrolimus (n=4), cyclosporine (n=4), or sirolimus (n=1). 7 of the transplanted patients accomplished the 12 week triple therapy. At week 4, 4 of the patients were found to be HCV RNA negative and importantly 8 at week 12. During the course of the 12 week triple therapy, short-termed measurements of immunosuppressant trough levels required individual dose reductions in all patients (cyclosporine 2.5 fold, sirolimus 7 fold, tacrolimus 22 fold, respectively). Furthermore, two thirds of patients exhibited hematological side effects requiring ribavirin dose reductions, administration of erythropoietin, or even blood transfusions. This pilot study provides evidence that telaprevir-based triple therapy is effective within the first 4 to 12 weeks in liver transplant patients suffering from HCV genotype 1 recurrence and also provides evidence that drug-drug interactions between telaprevir and the immunosuppressants can be handled appropriately by close monitoring of trough levels and adequate dosage adjustment.