Efficacy and safety of boceprevir-based triple therapy in HCV cirrhotic patients awaiting liver transplantation (ANRS HC29 BOCEPRETRANSPLANT)

Hélène Fontaine (1, 2) , Marianne Maynard (3) , Cécile Bouix (3) , Maria Patrizia Carrieri (4, 5) , Danielle Botta-Fridlund (6) , Louis d'Alteroche (7) , Antoine Conti (8) , Georges-Philippe Pageaux (9) , Vincent Leroy (10) , Sophie Métivier (11) , Rodolphe Anty (12) , François Durand (13) , Valérie Canva (14) , Antoine Vilotitch (4, 5) , Pascal Lebray (15) , Laurent Alric (16) , Christophe Duvoux (17) , Ventzislava Petrov-Sanchez (18, 19, 20) , Frédérik Beaulieux (3) , Célia Wellems (3) , Christelle Paul (18, 19) , Anne-Marie Roque-Afonso (21, 22) , Bruno Roche (21, 22) , Pierre Pradat (3) , Didier Samuel (21, 22) , Jean-Charles Duclos-Vallée (21, 22) , Bocepretransplant Study Group

1 Département d'hépatologie [CHU Cochin]
2 UPD5 - Université Paris Descartes - Paris 5
3 Service d'Hépatologie [Hôpital de la Croix-Rousse - HCL]
4 SESSTIM - U912 INSERM - Aix Marseille Univ - IRD - Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale
5 ORS PACA
6 LA CONCEPTION - Hôpital de la Conception [CHU - APHM]
7 Département d'Hépato-Gastroentérologie [Hôpital Trousseau, Tours]
8 CHU Saint-Antoine [AP-HP]
9 Fédération Médico-Chirurgicale des Maladies de l'Appareil Digestif
10 Département d'hépato-gastroentérologie
11 Pôle Maladies de l'appareil digestif [CHU Toulouse]
12 CHU Nice - Centre Hospitalier Universitaire de Nice
13 Service d’Hépatologie [Hôpital Beaujon]
14 Hôpital Claude Huriez [Lille]
15 CHU Pitié-Salpêtrière [AP-HP]
16 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
17 Service d'hépato-gastro-entérologie [APHP Henri Mondor]
18 ANRS France Recherche Nord & sud Sida-hiv hépatites
19 France REcherche Nord & sud Sida-hiv Hépatites (FRENSH)
20 Unit for Basic and Clinical research on Viral Hepatitis
21 CHB - Centre hépato-biliaire
22 Physiopathologie et traitement des maladies du foie

BACKGROUND AND AIMS: In this French multicentre, open-label study, we analyzed the efficacy, safety and patient-reported outcomes of a boceprevir-based triple therapy in HCV genotype 1 cirrhotic patients awaiting liver transplantation (LT). METHODS: Patients received PEG-IFN/ribavirin (RBV) for 48 weeks (W) and boceprevir from W4 to W48 or until LT. RESULTS: Fifty-one patients (80% males, median age: 56 years) were included. Fifty-seven percent had hepatocellular carcinoma and 43% end-stage liver disease. At enrolment, the median MELD score was 9 (range: 6-18); the Child-Pugh score was A in 65%, B in 35% and C in 2%. Therapy was discontinued because of severe adverse events (SAEs) in 39% of cases and virological inefficacy in 24%. 16% of patients had undetectable HCV RNA 24 weeks after the end of treatment (SVR24). LT was performed in 18 patients (35%). HCV RNA was undetectable in 16.6% at LT. Seven patients (14%) died and three deaths were attributed to treatment. SAEs (n=129) were observed in 84% of patients. Twenty-four percent of patients developed severe infections. Albumin<35g/L was independently associated with severe infection. Compared with baseline values, a significant decrease (P=0.02) of the physical dimension of health-related quality of life was observed between W4 and W24. The mean (95% CI) number of self-reported symptoms doubled during treatment (from 6.3 [4.8-7.7] to 11.8 [9.3-14.3]; P<0.001). CONCLUSIONS: The safety of the PEG-IFN/RBV/boceprevir combination is poor in patients awaiting LT, with a high risk of severe infection. Moreover, the limited efficacy confirms the indication for IFN-free combinations in these patients.

Domaines: Hépatologie et Gastroentérologie

Hélène Fontaine, Marianne Maynard, Cécile Bouix, Maria Patrizia Carrieri, Danielle Botta-Fridlund, et al.. Efficacy and safety of boceprevir-based triple therapy in HCV cirrhotic patients awaiting liver transplantation (ANRS HC29 BOCEPRETRANSPLANT). Clinics and Research in Hepatology and Gastroenterology, 2017, 41 (1), pp.56 - 65. ⟨10.1016/j.clinre.2016.06.006⟩. ⟨hal-01813216⟩