title: Sofosbuvir-based treatment of hepatitis C with severe fibrosis (METAVIR F3/F4) after liver transplantation.
abstract: Recurrence of hepatitis C virus (HCV) after liver transplantation (LT) can rapidly lead to liver graft cirrhosis and, therefore, graft failure and retransplantation or death. The aim of the present study was to assess efficacy and tolerance of sofosbuvir (SOF)-based regimens for the treatment of HCV recurrence in patients with severe fibrosis after LT. The Compassionate Use of Protease Inhibitors in Viral C Liver Transplantation (CULPIT) study is a prospective multicenter cohort including patients with HCV recurrence following LT treated with second generation direct antivirals. The present study focused on patients included between October 2013 and November 2014 and diagnosed with HCV recurrence and liver graft extensive fibrosis (METAVIR F3/F4). A SOF-based regimen was administered to 125 patients fulfilling inclusion criteria. The median delay from LT was 95.9 ± 69.6 months. The characteristics of patients were as follows: mean age, 59.4 ± 9.0 years; 78.4% male; infected by HCV genotype 1: 78.2%, mean HCV RNA: 6.1 ± 1.0 log10 IU/mL. Eighty patients had failed previous post-LT antiviral therapy (64.0%) including triple therapy with first generation protease inhibitors in 19 (15.2%) patients. The main combination regimen was SOF/daclatasvir (73.6%). Ribavirin was used in 60 patients. Sustained virological response 12 weeks after treatment was 92.8% (on an intention-to-treat basis); 7 patients with virological failure were observed. Serious adverse events occurred in 25.6% of the patients during antiviral treatment. During antiviral treatment and follow-up, 3 patients were retransplanted and 4 patients died. In conclusion, SOF-based antiviral treatment shows very promising results in patients with HCV recurrence and severe fibrosis after LT. Liver Transplantation 22 1367-1378 2016 AASLD.
authors.affiliation: Hospices Civils de Lyon, Hôpital Edouard Herriot, Université Claude Bernard Lyon 1, Lyon, France. jerome.dumortier@chu-lyon.fr.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Dumortier
authors.affiliation: Pôle Digidune, Clinique Universitaire d'Hépato-Gastroentérologie, Centre Hospitalier Universitaire de Grenoble, INSERM/Université Grenoble Alpes U823, Institut Albert Bonniot, Grenoble, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Leroy
authors.affiliation: Service d'Hépatologie, Hôpital Henri Mondor, AP-HP, Créteil, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Duvoux
authors.affiliation: Service d'Hépatologie, Hôpital Haut-Lévêque, Centre Hospitalier Universitaire de Bordeaux, INSERM U1053, Université Bordeaux, Bordeaux, France.
authors.forename: Victor
authors.initials: V
authors.lastname: de Ledinghen
authors.affiliation: Service d'Hépatologie, Hôpital Beaujon, AP-HP, Université Paris Diderot et INSERM U1149, Centre de Recherche sur l'Inflammation, Clichy, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Francoz
authors.affiliation: Service des Maladies du Foie, Centre Hospitalier Universitaire de Rennes, Rennes, France.
authors.forename: Pauline
authors.initials: P
authors.lastname: Houssel-Debry
authors.affiliation: Service d'Hépatologie, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Radenne
authors.affiliation: Service d'hépato-gastroentérologie, Centre Hospitalier Universitaire Trousseau, Tours, France.
authors.forename: Louis
authors.initials: L
authors.lastname: d'Alteroche
authors.affiliation: Unité de Pharmacologie Clinique, Centre Hospitalier Universitaire de Rennes, Centre d'Investigation Clinique INSERM 1414, Rennes, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Fougerou-Leurent
authors.affiliation: Services Maladies de l'Appareil Digestif, Hôpital Claude Huriez, Centre Hospitalier Universitaire de Lille, Lille, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Canva
authors.affiliation: Service d'Hépatologie, Hôpital Jean Minjoz, Centre Hospitalier Universitaire de Besançon, Université de Franche Comté, Besançon, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: di Martino
authors.affiliation: Service d'hépato-gastroentérologie, Groupe Hospitalier Pitié-Salpétrière, AP-HP, Université Pierre et Marie Curie Paris 6, INSERM Unités Mixtes de Recherche S938, Paris, France.
authors.forename: Filomena
authors.initials: F
authors.lastname: Conti
authors.affiliation: Département de Néphrologie et de Transplantation d'Organes, Centre Hospitalier Universitaire Rangueil, Université de Toulouse, Toulouse, France.
authors.forename: Nassim
authors.initials: N
authors.lastname: Kamar
authors.affiliation: Cliniques Universitaires de Bruxelles, Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: Moreno
authors.affiliation: Service d'hépato-gastroentérologie, Groupe Hospitalier Pitié-Salpétrière, AP-HP, Université Pierre et Marie Curie Paris 6, INSERM Unités Mixtes de Recherche S938, Paris, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Lebray
authors.affiliation: Service d'Hépatologie, Hôpital de l'Archet 2, Centre Hospitalier Universitaire de Nice, INSERM U1065, Université de Nice-Sophia-Antipolis, Nice, France.
authors.forename: Albert
authors.initials: A
authors.lastname: Tran
authors.affiliation: Service de Transplantation, Centre Hospitalier Universitaire de Strasbourg, Strasbourg, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Besch
authors.affiliation: Unit for Basic and Clinical Research on Viral Hepatitis, France Recherche Nord&Sud Sida-HIV Hépatites, Agence Nationale de Recherche sur le Sida, Paris, France.
authors.forename: Alpha
authors.initials: A
authors.lastname: Diallo
authors.affiliation: Unit for Basic and Clinical Research on Viral Hepatitis, France Recherche Nord&Sud Sida-HIV Hépatites, Agence Nationale de Recherche sur le Sida, Paris, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Rohel
authors.affiliation: Unité de Pharmacologie Clinique, Centre Hospitalier Universitaire de Rennes, Centre d'Investigation Clinique INSERM 1414, Rennes, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Rossignol
authors.affiliation: Service d'Hépato-Gastroentérologie, Centre Hospitalier Universitaire Estaing, Université d'Auvergne, Unités Mixtes de Recherche CNRS 6284, Clermont-Ferrand, France.
authors.forename: Armand
authors.initials: A
authors.lastname: Abergel
authors.affiliation: Service d'hépato-gastroentérologie, Hôpital de la Conception, AP-HM, Marseille, France.
authors.forename: Danielle
authors.initials: D
authors.lastname: Botta-Fridlund
authors.affiliation: Centre Hépato-Biliaire, Hôpital Paul Brousse, AP-HP, Université Paris-Sud, Université Paris-Saclay, UMR-S 1193, INSERM Unité 1193, Département Hospitalo-Universitaire Hepatinov, Villejuif, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Coilly
authors.affiliation: Centre Hépato-Biliaire, Hôpital Paul Brousse, AP-HP, Université Paris-Sud, Université Paris-Saclay, UMR-S 1193, INSERM Unité 1193, Département Hospitalo-Universitaire Hepatinov, Villejuif, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Samuel
authors.affiliation: Centre Hépato-Biliaire, Hôpital Paul Brousse, AP-HP, Université Paris-Sud, Université Paris-Saclay, UMR-S 1193, INSERM Unité 1193, Département Hospitalo-Universitaire Hepatinov, Villejuif, France.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Duclos-Vallée
authors.affiliation: Département d'Hépato-Gastroentérologie et de Transplantation Hépatique, Centre Hospitalier Universitaire Saint-Eloi, Université de Montpellier, Montpellier, France.
authors.forename: Georges-Philippe
authors.initials: GP
authors.lastname: Pageaux
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D001530:Belgium; D002219:Carbamates; D057176:Compassionate Use Trials; D005260:Female; D005602:France; D005838:Genotype; D016174:Hepacivirus; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000821:virology; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011480:Protease Inhibitors / Q000627:therapeutic use*; D011759:Pyrrolidines; D012008:Recurrence; D012086:Reoperation; D012254:Ribavirin / Q000627:therapeutic use; D000069474:Sofosbuvir / Q000627:therapeutic use*; D016896:Treatment Outcome; D014633:Valine / Q000031:analogs & derivatives
chemical_list: D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D007166:Immunosuppressive Agents; D011480:Protease Inhibitors; D011759:Pyrrolidines; D012254:Ribavirin; D014633:Valine; C549273:daclatasvir; D000069474:Sofosbuvir