Feasibility of Telaprevir-Based Triple Therapy in Liver Transplant Patients with Hepatitis C Virus: SVR 24 Results

Christoph R Werner,Alfred Königsrainer,Nisar P Malek,Silvio Nadalin,Ulrich M Lauer,Daniel P Egetemeyr,Christoph P Berg,Ming-Lung Yu

doi:10.1371/journal.pone.0080528

Abstract

Management of recurrent Hepatitis C virus (HCV) infection following liver transplantation remains a major challenge. In non-transplanted HCV genotype 1 patients, the introduction of protease inhibitor-based regimens has significantly increased the rate of sustained virological response. In this follow-up study, on the first published cohort of post-liver transplant patients treated with telaprevir-based triple therapy, we investigated both efficacy and safety data in follow-up to 24 weeks (SVR 24) after end of treatment (EOT). SVR 24 efficacy and safety data from 9 liver transplant HCV patients being treated with telaprevir, pegylated interferon, and ribavirin, showed 5 of the transplanted patients accomplished the full duration of the 48 week triple therapy. Notable were the 4 patients found to be HCV RNA-negative at week 4, and 8 patients at week 12. Upon EOT, at week 48, 6 patients were HCV RNA-negative. Importantly, at follow-up (24 weeks after EOT), a favorable sustained virological response rate was observed in 5 of these patients with HCV RNA remaining negative, including in one patient who discontinued treatment prematurely. Due to side effects, 2 patients discontinued, 2 suffered from virological breakthrough after the telaprevir treatment phase, and 1 patient had a relapse after EOT. Two thirds of patients exhibited hematological side effects requiring ribavirin dose reductions, administration of erythropoetin, or even blood transfusions. This retrospective analysis provides evidence that - with respect to SVR 24 - liver transplant patients suffering from HCV genotype 1 recurrence may benefit from a telaprevir-based triple therapy as this new regimen showed acceptable antiviral efficacy in this small cohort of mostly pre-treated patients. Management of drug-drug interactions is challenging, but feasible. In part severe side effects are frequent during treatment and require therapeutic interventions.

Highlights

In 2011 the first direct acting antivirals (DAA), the drug class of protease inhibitors (PI) represented by boceprevir and telaprevir (TVR), were approved by the authorities for treatment of chronic Hepatitis C virus (HCV) genotype 1 infections
Due to superior antiviral efficacy in combination with pegylated interferon (PEG-IFN) and ribavirin (RBV) their use was quickly adopted in the clinic [1,2] even though management of side effects was more time intensive and costly, compared to the former dual therapy with PEG-IFN and RBV alone
The immunosuppressive regimens were heterogeneous: 4 patients received tacrolimus (TAC), 4 patients were on cyclosporine A (CSA), and 1 patient received sirolimus (SIR) as the main immunosuppressive agent. 4 patients were given mycophenolate mofetil (MMF) as co-medication. 5 patients received low-dose steroids (2.5 - 5 mg/day; Table 1). 7 patients with HCV genotype 1b and 2 patients with HCV genotype 1a were included in our study

Summary

Introduction

In 2011 the first direct acting antivirals (DAA), the drug class of protease inhibitors (PI) represented by boceprevir and telaprevir (TVR), were approved by the authorities for treatment of chronic Hepatitis C virus (HCV) genotype 1 infections. Following successful treatment of HCV, post-LT patients have been shown to exhibit significantly reduced morbidity rates corresponding to increased survival times [3,4] The translation of this superior antiviral efficacy of PI-based triple therapies from non-LT to post-LT patients constitutes a very attractive goal [5,6,7]. In recent work we have been able to demonstrate that management of a TVR-based triple therapy regimen in patients post-LT is feasible with respect to drug-drug interactions, side effects were common [9] In this small pilot study the viral response was shown to be excellent with no treated patients showing any detectable HCV viral load at the end of the TVR phase of the TVR-based triple therapy (treatment week 12)[9]. The aim of this follow-up study is to retrospectively evaluate the antiviral efficacy and safety of the TVR triple therapy in post-LT patients with respect to sustained viral response rates 24 weeks (SVR 24) after planned discontinuation of PEG-IFN and RBV (week 48 of treatment)

Patients and Methods

Results

Discussion