Original Article
Copyright ©2014 Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Sep 27, 2014; 6(9): 660-669
Published online Sep 27, 2014. doi: 10.4254/wjh.v6.i9.660
Telaprevir- and boceprevir-based tritherapies in real practice for F3-F4 pretreated hepatitis C virus patients
Delphine Bonnet, Matthieu Guivarch, Emilie Bérard, Jean-Marc Combis, Andre Jean Remy, Andre Glibert, Jean-Louis Payen, Sophie Metivier, Karl Barange, Herve Desmorat, Anaïs Palacin, Florence Nicot, Florence Abravanel, Laurent Alric
Delphine Bonnet, Matthieu Guivarch, Anaïs Palacin, Laurent Alric, Internal Medicine-Digestive Department, Purpan University Hospital, 31059 Toulouse cedex 9, France
Emilie Bérard, Department of Epidemiology, Health Economics and Public Health, Toulouse University Hospital, 31073 Toulouse, France
Emilie Bérard, UMR-1027 INSERM-Toulouse III University, 31062 Toulouse, France
Jean-Marc Combis, Clinique Ambroise Pare, 31300 Toulouse, France
Andre Jean Remy, Perpignan General Hospital, 66000 Perpignan, France
Andre Glibert, Tarbes General Hospital, 65000 Tarbes, France
Jean-Louis Payen, Montauban General Hospital, 82000 Montauban, France
Sophie Metivier, Karl Barange, Hepatogastroenterology-Digestive Department, Purpan University Hospital, 31059 Toulouse cedex 9, France
Herve Desmorat, Clinique du Parc, 31078 Toulouse Cedex 4, France
Florence Nicot, Florence Abravanel, Virology Unit INSERM U1043, 31059 Toulouse cedex 9, France
Laurent Alric, UMR152 IRD Toulouse III University, 31400 Toulouse, France
Author contributions: Bonnet D and Guivarch M equally contributed to the work; Bonnet D contributed to planning and conducting the study, collecting and interpreting the data, drafting the manuscript; Guivarch M contributed to planning and conducting the study, collecting and interpreting the data, drafting the manuscript; Berard E contributed to biostatistical analysis and interpretating the data, drafting the manuscript; Combis JM, Remy AJ, Glibert A, Payen JL, Desmorat H, Metivier S and Barange K contributed to treatment of patients; Palacin A contributed to collecting data; Nicot F contributed to viral monitoring; Abravanel F contributed to viral monitoring; Alric L contributed to treatment of patients, planning and conducting the study, interpreting the data, drafting the manuscript.
Correspondence to: Laurent Alric, Professor, Internal Medecine, Digestive Department, Pavillon Dieulafoy, CHU Purpan, TSA 40031, Toulouse 31059 cedex, France. alric.l@chu-purpan-toulouse.fr
Telephone: +33-5-61779551 Fax: +33-5-61772230
Received: February 19, 2014
Revised: June 30, 2014
Accepted: August 27, 2014
Published online: September 27, 2014
Processing time: 242 Days and 16.4 Hours
Abstract

AIM: To assess, in a routine practice setting, the sustained virologic response (SVR) to telaprevir (TPV) or boceprevir (BOC) in hepatitis C virus (HCV) null-responders or relapsers with severe liver fibrosis.

METHODS: One hundred twenty-five patients were treated prospectively for 48 wk with TPV or BOC + pegylated-interferon (peg-INF) α2a + ribavirin (PR) according to standard treatment schedules without randomization. These patients were treated in routine practice settings in 10 public or private health care centers, and the data were prospectively collected. Only patients with severe liver fibrosis (Metavir scores of F3 or F4 upon liver biopsy or liver stiffness assessed by elastography), genotype 1 HCV and who were null-responders or relapsers to prior PR combination therapy were included in this study.

RESULTS: The Metavir fibrosis scores were F3 in 35 (28%) and F4 in 90 (72%) of the patients. In total, 62.9% of the patients were null-responders and 37.1% relapsers to the previous PR therapy. The overall SVR rate at 24 wk post-treatment withdrawal was 59.8%. The SVR was 65.9% in the TPV group and 44.1% in the BOC group. Independent predictive factors of an SVR included a response to previous treatment, relapsers vs null-responders [OR = 3.9; (1.4, 10.6), P = 0.0084], a rapid virological response (RVR) [OR 6.9 (2.6, 18.2), P = 0.001] and liver stiffness lower than 21.3 kPa [OR = 8.2 (2.3, 29.5), P = 0.001]. During treatment, 63 patients (50.8%) had at least one severe adverse event (SAE) of grade 3 or 4. A multivariate analysis identified two factors associated with SAEs: female gender [OR = 2.4 (1.1, 5.6), P = 0.037] and a platelet count below 150 × 103/ mm3 [OR = 5.3 (2.3, 12.4), P≤ 0.001].

CONCLUSION: More than half of these difficult-to-treat patients achieved an SVR and had SAEs in an actual practice setting. The SVR rate was influenced by the response to previous PR treatment, the RVR and liver stiffness.

Keywords: Hepatitis C virus; Hepatitis C; Antiviral therapy; Protease inhibitors; Fibroscan; Liver stiffness; Cirrhosis; Boceprevir; Telaprevir; Ribavirin

Core tip: To the best of our knowledge, this study marks the first time that a significant link has been shown between a sustained virological response to triple therapy and the liver stiffness measured by elastography at baseline. We also demonstrate that triple therapy is poorly tolerated. Two factors predict the development of serious adverse events: female gender and an initial platelet count of less than 150000/mm3; these factors facilitate the identification of at-risk patients.