title: Multicenter Experience with Boceprevir or Telaprevir to Treat Hepatitis C Recurrence after Liver Transplantation: When Present Becomes Past, What Lessons for Future?
abstract: OBJECTIVE
  First generation protease inhibitors (PI) with peg-interferon (PEG-IFN) and ribavirin (RBV) have been the only therapy available for hepatitis C virus (HCV) genotype 1 infection in most countries for 3 years. We have investigated the efficacy and tolerance of this triple therapy in transplanted patients experiencing a recurrence of HCV infection on the liver graft.
  
  
  METHODS
  This cohort study enrolled 81 liver transplant patients (Male: 76%, mean age: 55.8±9.7 years) with severe HCV recurrence (F3 or F4: n = 34 (42%), treatment experienced: n = 44 (54%)), treated with boceprevir (n = 36; 44%) or telaprevir (n = 45; 56%). We assessed the percentages of patients with sustained virological responses 24 weeks after therapy (SVR24), and safety.
  
  
  RESULTS
  The SVR24 rate was 47% (telaprevir: 42%; boceprevir: 53%, P = ns). At baseline, a normal bilirubin level (p = 0.0145) and albumin level >35g/L (p = 0.0372) and an initial RBV dosage of ≥800 mg/day (p = 0.0033) predicted SVR24. During treatment, achieving an early virological response after 12 weeks was the strongest independent factor to predict SVR24 (p<0.0001). A premature discontinuation of anti-HCV therapy due to a serious adverse event (SAE) was observed in 22 patients (27%). Hematological toxicity, infections and deaths were observed in 95%, 28% and 7% of patients, respectively. A history of post-LT antiviral therapy and thrombocytopenia (<50G/L) during treatment were both independent predictors of the occurrence of infections or SAE (p = 0.0169 and p = 0.011).
  
  
  CONCLUSIONS
  The use of first generation PI after liver transplantation enabled an SVR24 rate of 47% in genotype 1 patients, but induced a high rate of SAE. The identification of predictive factors for a response to treatment, and the occurrence of SAE, have enabled us to establish limits for the use of this anti-HCV therapy in the transplant setting.
authors.affiliation: AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, F-94800, France, Université Paris-Sud, UMR-S 785, Villejuif, F-94800, France, Inserm, Unité 785, Villejuif, F-94800, France, Hepatinov, Villejuif, F-94800, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Coilly
authors.affiliation: Department of Digestive Diseases, Hospices Civils de Lyon, Edouard Herriot Hospital, Lyon, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Dumortier
authors.affiliation: Assistance Publique-Hôpitaux de Marseille, Centre Hospitalo-Universitaire Conception, Service d'Hépato-Gastro-Entérologie, Marseille, France.
authors.forename: Danielle
authors.initials: D
authors.lastname: Botta-Fridlund
authors.affiliation: CHU Rennes, Liver Disease Unit, Rennes, France.
authors.forename: Marianne
authors.initials: M
authors.lastname: Latournerie
authors.affiliation: Service d'hépato-gastro-entérologie, hôpital A.-Michallon, 38700, La Tronche, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Leroy
authors.affiliation: Fédération médico-chirurgicale des maladies de l'appareil digestif, hôpital Saint-Eloi, 34295, Montpellier, France.
authors.forename: Georges-Philippe
authors.initials: GP
authors.lastname: Pageaux
authors.affiliation: AP-HP, Hôpital Bicêtre, Unité de recherche clinique Paris-Sud, Kremlin-Bicêtre, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Agostini
authors.affiliation: Department of Gastroenterology and Hepatology, Geneva University Hospital, Rue Gabrielle-Perret-Gentil 4, 1211, Geneva, 14, Switzerland.
authors.forename: Emiliano
authors.initials: E
authors.lastname: Giostra
authors.affiliation: Liver unit, Department of Gastroenterology, Hepatopancreatology and Digestive oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: Moreno
authors.affiliation: AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, F-94800, France, Université Paris-Sud, UMR-S 785, Villejuif, F-94800, France, Inserm, Unité 785, Villejuif, F-94800, France, Hepatinov, Villejuif, F-94800, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Roche
authors.affiliation: AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, F-94800, France, Université Paris-Sud, UMR-S 785, Villejuif, F-94800, France, Inserm, Unité 785, Villejuif, F-94800, France, Hepatinov, Villejuif, F-94800, France.
authors.forename: Teresa Maria
authors.initials: TM
authors.lastname: Antonini
authors.affiliation: Department of Digestive Diseases, Hospices Civils de Lyon, Edouard Herriot Hospital, Lyon, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Guillaud
authors.affiliation: Assistance Publique Hôpitaux de Paris (AP-HP), Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Lebray
authors.affiliation: Service d'hépatologie, HCL, hôpital de la Croix-Rousse, 69205, Lyon, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Radenne
authors.affiliation: Hepato-Bilio-Pancreatic Surgery and Liver Transplantation Center, Université de Strasbourg, Strasbourg, France.
authors.forename: Anne-Catherine
authors.initials: AC
authors.lastname: Saouli
authors.affiliation: Department of Hepatobiliary and Liver Transplantation Surgery, Hopital Saint Antoine, Assistance publique-Hopitaux de Paris, 184 rue du Faubourg Saint-Antoine, 75012, Paris Cedex, France.
authors.forename: Yvon
authors.initials: Y
authors.lastname: Calmus
authors.affiliation: Internal medecine-Digestive department UMR 152 IRD Toulouse 3 University, Toulouse, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Alric
authors.affiliation: Service d'Hépato-gastroentérologie, CHU de Limoges, 2 avenue Martin-Luther-King, 87042, Limoges, France, Inserm UMR 1092, Faculté de médecine de Limoges, Université de Limoges, Limoges, France.
authors.forename: Maryline
authors.initials: M
authors.lastname: Debette-Gratien
authors.affiliation: University of Bordeaux, Bordeaux, France.
authors.forename: Victor
authors.initials: V
authors.lastname: De Ledinghen
authors.affiliation: Service d'hépatologie, hôpital Beaujon, AP-HP, 92118, Clichy, France.
authors.forename: François
authors.initials: F
authors.lastname: Durand
authors.affiliation: Service d'hépatologie, hôpital Henri-Mondor, AP-HP, 94000, Créteil, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Duvoux
authors.affiliation: AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, F-94800, France, Université Paris-Sud, UMR-S 785, Villejuif, F-94800, France, Inserm, Unité 785, Villejuif, F-94800, France, Hepatinov, Villejuif, F-94800, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Samuel
authors.affiliation: AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, F-94800, France, Université Paris-Sud, UMR-S 785, Villejuif, F-94800, France, Inserm, Unité 785, Villejuif, F-94800, France, Hepatinov, Villejuif, F-94800, France.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Duclos-Vallée
mesh_terms: D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced; D000998:Antiviral Agents / Q000009:adverse effects / Q000494:pharmacology; D003131:Combined Modality Therapy; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D006526:Hepatitis C / Q000235:genetics / Q000628:therapy* / Q000821:virology; D054884:Host-Pathogen Interactions / Q000187:drug effects; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects / Q000494:pharmacology; D016031:Liver Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009842:Oligopeptides / Q000009:adverse effects / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000494:pharmacology; D011184:Postoperative Period; D011392:Proline / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D011446:Prospective Studies; D011480:Protease Inhibitors / Q000009:adverse effects / Q000494:pharmacology; D011994:Recombinant Proteins / Q000009:adverse effects / Q000494:pharmacology; D012008:Recurrence; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D009842:Oligopeptides; D011480:Protease Inhibitors; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C486464:telaprevir; 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; C100416:peginterferon alfa-2a