title: Safety and efficacy of protease inhibitors to treat hepatitis C after liver transplantation: a multicenter experience.
abstract: OBJECTIVE
  Protease inhibitors (PI) with peginterferon/ribavirin have significantly improved SVR rates in HCV G1 patients. Their use to treat HCV recurrence after liver transplantation (LT) is a challenge.
  
  
  METHODS
  This cohort study included 37 liver transplant recipients (male, 92%, age 57 ± 11 years), treated with boceprevir (n=18) or telaprevir (n=19). The indication for therapy was HCV recurrence (fibrosis stage ≥F2 (n=31, 83%) or fibrosing cholestatic hepatitis (n=6, 16%).
  
  
  RESULTS
  Eighteen patients were treatment-naive, five were relapsers and fourteen were non-responders to dual therapy after LT. Twenty-two patients received cyclosporine and fifteen tacrolimus. After 12 weeks of PI therapy, a complete virological response was obtained in 89% of patients treated with boceprevir, and 58% with telaprevir (p=0.06). The end of treatment virological response rate was 72% (13/18) in the boceprevir group and 40% (4/10) in the telaprevir group (p=0.125). A sustained virological response 12 weeks after treatment discontinuation was observed in 20% (1/5) and 71% (5/7) of patients in the telaprevir and boceprevir groups, respectively (p=0.24). Treatment was discontinued in sixteen patients (treatment failures (n=11), adverse events (n=5)). Infections occurred in ten patients (27%), with three fatal outcomes (8%). The most common adverse effect was anemia (n=34, 92%), treated with erythropoietin and/or a ribavirin dose reduction; thirteen patients (35%) received red blood cell transfusions. The cyclosporine dose was reduced by 1.8 ± 1.1-fold and 3.4 ± 1.0-fold with boceprevir and telaprevir, respectively. The tacrolimus dose was reduced by 5.2 ± 1.5-fold with boceprevir and 23.8±18.2-fold with telaprevir.
  
  
  CONCLUSIONS
  Our results suggest that triple therapy is effective in LT recipients, particularly those experiencing a severe recurrence. The occurrence of anemia and drug-drug interactions, and the risk of infections require close monitoring.
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: 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: Hôpital Edouard Herriot, Unité de transplantation hépatique, Lyon F-69400, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Dumortier
authors.affiliation: CHU de Grenoble, Clinique universitaire d'hépato-gastroentérologie, Grenoble F-38000, France; Inserm, Unité 823, Grenoble F-38000, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Leroy
authors.affiliation: CHU Conception, Service d'hépato-gastroentérologie, Marseille F-13005, France.
authors.forename: Danielle
authors.initials: D
authors.lastname: Botta-Fridlund
authors.affiliation: Hôpital de la Croix Rousse, Service de transplantation hépatique, Lyon F-69300, France; Université Claude Bernard Lyon 1, Lyon F-69000, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Radenne
authors.affiliation: CHU Saint-Eloi, Département hépato-gastroentérologie et transplantation hépatique, Montpellier F-34200, France; Université Montpellier 1, Montpellier F-34000, France.
authors.forename: Georges-Philippe
authors.initials: GP
authors.lastname: Pageaux
authors.affiliation: Hôpital de la Croix Rousse, Service de transplantation hépatique, Lyon F-69300, France.
authors.forename: Si-Nafaa
authors.initials: SN
authors.lastname: Si-Ahmed
authors.affiliation: Hôpital Edouard Herriot, Unité de transplantation hépatique, Lyon F-69400, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Guillaud
authors.affiliation: AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif F-94800, France; Hepatinov, Villejuif F-94800, France.
authors.forename: Teresa Maria
authors.initials: TM
authors.lastname: Antonini
authors.affiliation: Université Paris-Sud, UMR-S 785, Villejuif F-94800, France; Inserm, Unité 785, Villejuif F-94800, France; Hepatinov, Villejuif F-94800, France; AP-HP Hôpital Paul-Brousse, Laboratoire de Virologie, Villejuif F-94800, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Haïm-Boukobza
authors.affiliation: Université Paris-Sud, UMR-S 785, Villejuif F-94800, France; Inserm, Unité 785, Villejuif F-94800, France; Hepatinov, Villejuif F-94800, France; AP-HP Hôpital Paul-Brousse, Laboratoire de Virologie, Villejuif F-94800, France.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Roque-Afonso
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. Electronic address: jean-charles.duclos-vallee@pbr.aphp.fr.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Duclos-Vallée
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011480:Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D011480:Protease Inhibitors
keywords: AFEF; ALT; AUC; BID; BOC; Boceprevir; CNI; CYP; Drug-drug interaction; EOT; EPO; EVR; Early virological response; F; FCH; French Association for the Study of the Liver; G-CSF; G1; GGT; HBV; HCC; HCV; HCV recurrence; HIV; IL; INR; IS; International Normalized Ratio; LT; Liver transplantation; M; MELD; MMF; Model for End-stage Liver Disease; NR; PCR; PI; PegIFN; Protease inhibitors; QD; RBV; RVR; SVR12; Sustained virological response; TBC; TID; TVR; Telaprevir; VB; VL; VR; alanine aminotransferase; area under the curve; boceprevir; cEVR; calcineurin inhibitors; complete early virological response; cytochrome P450; early virological response; end of treatment response rate; erythropoietin; female; fibrosing cholestatic hepatitis; gamma-glutamyl transferase; genotype 1; granulocyte colony stimulating factor; hepatitis B virus; hepatitis C virus; hepatocellular carcinoma; human immunodeficiency virus; immunosuppressive drugs; interleukin; kg; kilogram; liver transplantation; male; mycophenolate mofetil; n.a.; non-response; not available; once a day (quaque die); pegylated interferon; polymerase chain reaction; protease inhibitors; rapid virological response; ribavirin; sustained virological response 12weeks after the end of therapy; telaprevir; three times a day (ter in die); trough blood concentration; twice daily (bis in die); viral load; virological breakthrough; virological response