title: Efficacy and safety of boceprevir-based triple therapy in HCV cirrhotic patients awaiting liver transplantation (ANRS HC29 BOCEPRETRANSPLANT).
abstract: OBJECTIVE
  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.
authors.affiliation: Université Paris Descartes, Inserm USM20, Institut Pasteur, Assistance publique-Hôpitaux de Paris, service d'hépatologie, hôpital Cochin, 27, rue du Faubourg-Saint-Jacques, 75014 Paris, France. Electronic address: helene.fontaine@cch.aphp.fr.
authors.forename: Hélène
authors.initials: H
authors.lastname: Fontaine
authors.affiliation: Department of hepatology, hôpital de la Croix-Rousse, hospices civils de Lyon, Lyon, France.
authors.forename: Marianne
authors.initials: M
authors.lastname: Maynard
authors.affiliation: Department of hepatology, hôpital de la Croix-Rousse, hospices civils de Lyon, Lyon, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Bouix
authors.affiliation: Inserm, UMR912 (SESSTIM), Marseille, France; Aix Marseille université, UMR_S912, IRD, Marseille, France; Observatoire Régional de la Santé Provence-Alpes-Côte-d'Azur (ORS PACA), Marseille, France.
authors.forename: Maria Patrizia
authors.initials: MP
authors.lastname: Carrieri
authors.affiliation: Department of Hepatology and Gastroenterology, Hôpital de la Conception, Marseille, France.
authors.forename: Danielle
authors.initials: D
authors.lastname: Botta-Fridlund
authors.affiliation: Department of Hepatology and Gastroenterology, Trousseau Hospital, Tours, France.
authors.forename: Louis
authors.initials: L
authors.lastname: D'Alteroche
authors.affiliation: Department of Hepatology, Saint-Antoine Hospital, Paris, France.
authors.forename: Filomena
authors.initials: F
authors.lastname: Conti
authors.affiliation: Fédération médico-chirurgicale des maladies de l'appareil digestif, Saint-Eloi, Montpellier, France.
authors.forename: Georges-Philippe
authors.initials: GP
authors.lastname: Pageaux
authors.affiliation: Department of Hepatology and Gastroenterology, La Tronche Hospital, Grenoble, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Leroy
authors.affiliation: Department of Hepatology and Gastroenterology, Purpan Hospital, Toulouse, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Métivier
authors.affiliation: Digestive Center, Hôpital de l'Archet, Nice, France.
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Anty
authors.affiliation: Department of Hepatology, Beaujon Hospital, AP-HP, Clichy, France.
authors.forename: François
authors.initials: F
authors.lastname: Durand
authors.affiliation: Department of Hepatology and Gastroenterology, Claude-Huriez Hospital, Lille, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Canva
authors.affiliation: Inserm, UMR912 (SESSTIM), Marseille, France; Aix Marseille université, UMR_S912, IRD, Marseille, France; Observatoire Régional de la Santé Provence-Alpes-Côte-d'Azur (ORS PACA), Marseille, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Vilotitch
authors.affiliation: Department of Hepatology and Gastroenterology, Pitié-Salpêtrière Hospital, Paris, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Lebray
authors.affiliation: Pôle digestif, Purpan Hospital, Toulouse, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Alric
authors.affiliation: Hepatology and Gastroenterology, Henri-Mondor Hospital, Créteil, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Duvoux
authors.affiliation: Unit for Basic and Clinical research on Viral Hepatitis, ANRS (France REcherche Nord & sud Sida-HIV Hépatites [FRENSH]), Paris, France.
authors.forename: Ventzislava
authors.initials: V
authors.lastname: Petrov-Sanchez
authors.affiliation: Department of hepatology, hôpital de la Croix-Rousse, hospices civils de Lyon, Lyon, France.
authors.forename: Frédérik
authors.initials: F
authors.lastname: Beaulieux
authors.affiliation: Department of hepatology, hôpital de la Croix-Rousse, hospices civils de Lyon, Lyon, France.
authors.forename: Célia
authors.initials: C
authors.lastname: Wellems
authors.affiliation: Clinical Trial Safety Office, ANRS (France REcherche Nord & sud Sida-HIV Hépatites [FRENSH]), Paris, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Paul
authors.affiliation: AP-HP, Hôpital Paul-Brousse, Centre Hépato-Biliaire, Inserm, Unit 1193, Université Paris-Sud, UMR-S1193, DHU Hepatinov, Villejuif, France.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Roque-Afonso
authors.affiliation: AP-HP, Hôpital Paul-Brousse, Centre Hépato-Biliaire, Inserm, Unit 1193, Université Paris-Sud, UMR-S1193, DHU Hepatinov, Villejuif, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Roche
authors.affiliation: Department of hepatology, hôpital de la Croix-Rousse, hospices civils de Lyon, Lyon, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Pradat
authors.affiliation: AP-HP, Hôpital Paul-Brousse, Centre Hépato-Biliaire, Inserm, Unit 1193, Université Paris-Sud, UMR-S1193, DHU Hepatinov, Villejuif, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Samuel
authors.affiliation: AP-HP, Hôpital Paul-Brousse, Centre Hépato-Biliaire, Inserm, Unit 1193, Université Paris-Sud, UMR-S1193, DHU Hepatinov, Villejuif, France.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Duclos-Vallée
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D004359:Drug Therapy, Combination; D005260:Female; D005602:France; D019698:Hepatitis C, Chronic / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000821:virology; D008113:Liver Neoplasms / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011392:Proline / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011788:Quality of Life; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D012254:Ribavirin; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; D011392:Proline