title: Eradication of Hepatitis C Virus Infection in Patients With Cirrhosis Reduces Risk of Liver and Non-Liver Complications.
abstract: We performed a prospective study to investigate the effects of a sustained viral response (SVR) on outcomes of patients with hepatitis C virus (HCV) infection and compensated cirrhosis.
  
  
  
  We collected data from 1323 patients included in the prospective Agence Nationale pour la Recherche sur le SIDA et les hépatites virales (ANRS) viral cirrhosis (CirVir) cohort, recruited from 35 clinical centers in France from 2006 through 2012. All patients had HCV infection and biopsy-proven cirrhosis, were Child-Pugh class A, and had no prior liver complications. All patients received anti-HCV treatment before or after inclusion (with interferon then with direct antiviral agents) and underwent an ultrasound examination every 6 months, as well as endoscopic evaluations. SVR was considered as a time-dependent covariate; its effect on outcome was assessed by the Cox proportional hazard regression method. We used a propensity score to minimize confounding by indication of treatment and capacity to achieve SVR.
  
  
  
  After a median follow-up period of 58.2 months, 668 patients (50.5%) achieved SVR. SVR was associated with a decreased incidence of hepatocellular carcinoma (hazard ratio [HR] compared with patients without an SVR, 0.29; 95% confidence interval [CI], 0.19-0.43; P < .001) and hepatic decompensation (HR, 0.26; 95% CI, 0.17-0.39; P < .001). Patients with SVRs also had a lower risk of cardiovascular events (HR, 0.42; 95% CI, 0.25-0.69; P = .001) and bacterial infections (HR, 0.44; 95% CI, 0.29-0.68; P < .001). Metabolic features were associated with a higher risk of hepatocellular carcinoma in patients with SVRs, but not in patients with viremia. SVR affected overall mortality (HR, 0.27 compared with patients without SVR; 95% CI, 0.18-0.42; P < .001) and death from liver-related and non-liver-related causes. Similar results were obtained in a propensity score-matched population.
  
  
  
  We confirmed a reduction in critical events, liver-related or not, in a prospective study of patients with HCV infection and compensated cirrhosis included in the CirVir cohort who achieved an SVR. We found an SVR to reduce overall mortality and risk of death from liver-related and non-liver-related causes. A longer follow-up evaluation is required to accurately describe and assess specific risk factors for complications in this population.
authors.affiliation: AP-HP, Hôpital Jean Verdier, Service d'Hépatologie, Bondy, France; Université Paris 13, Sorbonne Paris Cité, "Equipe Labellisée Ligue Contre le Cancer," Saint-Denis, France; Inserm, UMR-1162, "Génomique Fonctionnelle des Tumeur Solides," Paris, France. Electronic address: pierre.nahon@jvr.aphp.fr.
authors.forename: Pierre
authors.initials: P
authors.lastname: Nahon
authors.affiliation: AP-HP, Hôpital Jean Verdier, Service d'Hépatologie, Bondy, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Bourcier
authors.affiliation: AP-HP, Hôpital Henri Mondor, Département de Santé Publique, and Université Paris-Est, Ageing-Thorax-Vessels-Blood Département Hospitalo-Universitaire, Clinical Epidemiology and Aging Unit, Université Paris-Est Créteil, Créteil, France.
authors.forename: Richard
authors.initials: R
authors.lastname: Layese
authors.affiliation: AP-HP, Hôpital Henri Mondor, Département de Santé Publique, and Université Paris-Est, Ageing-Thorax-Vessels-Blood Département Hospitalo-Universitaire, Clinical Epidemiology and Aging Unit, Université Paris-Est Créteil, Créteil, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Audureau
authors.affiliation: Unit for Basic and Clinical Research on Viral Hepatitis, Association Nationale pour la Recherche sur le SIDA et les hépatites virales (ANRS), France REcherche Nord and sud Sida-HIV Hépatites, Paris, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Cagnot
authors.affiliation: AP-HP, Hôpital Beaujon, Service d'Hépatologie, Clichy, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Marcellin
authors.affiliation: Centre Hospitalo-Universitaire Pontchaillou, Service d'Hépatologie, Rennes, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Guyader
authors.affiliation: AP-HP, Hôpital Cochin, Département d'Hépatologie, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Fontaine
authors.affiliation: Hôpital Saint Eloi, Service d'Hépatologie, Montpellier, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Larrey
authors.affiliation: Hôpital Haut-Lévêque, Service d'Hépatologie, Bordeaux, France.
authors.forename: Victor
authors.initials: V
authors.lastname: De Lédinghen
authors.affiliation: Institut Arnaud Tzanck, Service d'Hépatologie, St Laurent du Var, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Ouzan
authors.affiliation: Hospices Civils de Lyon, Service d'Hépatologie et Université de Lyon, Lyon, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Zoulim
authors.affiliation: AP-HP, Hôpital Avicenne, Service d'Hépatologie, Bobigny, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Roulot
authors.affiliation: Centre Hospitalo-Universitaire de Nice, Service d'Hépatologie, Nice, France; Inserm U1065, C3M, Team 8, "Hepatic Complications in Obesity," Nice, France.
authors.forename: Albert
authors.initials: A
authors.lastname: Tran
authors.affiliation: Inserm 954, Centre Hospitalo-Universitaire de Nancy, Université de Lorraine, Vandoeuvre-les-Nancy, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bronowicki
authors.affiliation: Hôpital Michallon, Service d'Hépatologie, Grenoble, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Zarski
authors.affiliation: Hôpital Michallon, Service d'Hépatologie, Grenoble, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Leroy
authors.affiliation: Hôpital Charles-Nicolle, Service d'Hépatologie, Rouen, France.
authors.forename: Ghassan
authors.initials: G
authors.lastname: Riachi
authors.affiliation: Centre Hospitalo-Universitaire d'Angers, Service d'Hépato-Gastroentérologie, Angers, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Calès
authors.affiliation: Hôpital Purpan, Service d'Hépatologie, Toulouse, France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Péron
authors.affiliation: Centre Hospitalo-Universitaire Toulouse, Service de Médecine Interne-Pôle Digestif UMR 152, Toulouse, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Alric
authors.affiliation: Hôpital Saint Joseph, Service d'Hépatologie, Marseille, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Bourlière
authors.affiliation: Hôpital Claude Huriez, Service d'Hépatologie, Lille, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Mathurin
authors.affiliation: Hôpital Claude Huriez, Service d'Hépatologie, Lille, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Dharancy
authors.affiliation: Hôpital St André, Service d'Hépatologie, Bordeaux, France.
authors.forename: Jean-Frédéric
authors.initials: JF
authors.lastname: Blanc
authors.affiliation: Hôpital Hôtel Dieu, Service d'Hépatologie, Clermont-Ferrand, France.
authors.forename: Armand
authors.initials: A
authors.lastname: Abergel
authors.affiliation: AP-HP, Hôpital Saint-Antoine, Service d'Hépatologie, Paris, France.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Serfaty
authors.affiliation: AP-HP, Hôpital Henri Mondor, Service d'Hépatologie, Créteil, France.
authors.forename: Ariane
authors.initials: A
authors.lastname: Mallat
authors.affiliation: AP-HP, Hôpital Tenon, Service d'Hépatologie, Paris, France.
authors.forename: Jean-Didier
authors.initials: JD
authors.lastname: Grangé
authors.affiliation: AP-HP, Hôpital Paul Brousse, Service d'Hépatologie, Villejuif, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Attali
authors.affiliation: Hôpital Trousseau, Unité d'Hépatologie, Centre Hospitalier Régional Universitaire de Tours, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Bacq
authors.affiliation: Hôpital d'Aix-en-Provence, Service d'Hépatologie, Aix-En-Provence, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Wartelle
authors.affiliation: Hôpital de la Côte de Nacre, Service d'Hépatologie, Caen, France.
authors.forename: Thông
authors.initials: T
authors.lastname: Dao
authors.affiliation: AP-HP, Groupe Hospitalier de La Pitié-Salpêtrière, Service d'Hépatologie, Paris, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Benhamou
authors.affiliation: Centre Hospitalo-Universitaire Le Mans, Service d'Hépatologie, Le Mans, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Pilette
authors.affiliation: Centre Hospitalo-Universitaire de Poitiers, Service d'Hépatologie, Poitiers, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Silvain
authors.affiliation: Institut Mutualiste Montsouris, Service d'Hépatologie, Paris, France.
authors.forename: Christos
authors.initials: C
authors.lastname: Christidis
authors.affiliation: Hôpital Amiens Nord, Service d'Hépatologie, Amiens, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Capron
authors.affiliation: Hôpital Robert Debré, Service d'Hépatologie, Reims, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Bernard-Chabert
authors.affiliation: Hôpital Foch, Service de Médecine Interne, Suresnes, France.
authors.forename: David
authors.initials: D
authors.lastname: Zucman
authors.affiliation: Hôpital Jean Minjoz, Service d'Hépatologie, Besançon, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Di Martino
authors.affiliation: Centre Hospitalo-Universitaire Pontchaillou, Service de Virologie, Rennes, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Thibaut
authors.affiliation: AP-HP, Hôpital Cochin, Service de Maladies Infectieuses, Université Paris Descartes, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Salmon
authors.affiliation: Université Paris 13, Sorbonne Paris Cité, "Equipe Labellisée Ligue Contre le Cancer," Saint-Denis, France; Inserm, UMR-1162, "Génomique Fonctionnelle des Tumeur Solides," Paris, France; AP-HP, Hôpital Jean Verdier, Service d'Anatomopathologie, Bondy, France; Centre de Ressources Biologiques (Liver Disease Biobank) Groupe Hospitalier Paris, Seine-Saint-Denis, France.
authors.forename: Marianne
authors.initials: M
authors.lastname: Ziol
authors.affiliation: Centre de Ressources Biologiques (Liver Disease Biobank) Groupe Hospitalier Paris, Seine-Saint-Denis, France; AP-HP, Hôpital Jean Verdier, Service de Biochimie, Bondy, France; Inserm U1148, Université Paris 13, Bobigny, France.
authors.forename: Angela
authors.initials: A
authors.lastname: Sutton
authors.affiliation: AP-HP, Hôpital Cochin, Département d'Hépatologie, France; Inserm UMS20 et U1223, Institut Pasteur, Université Paris Descartes, Paris, France.
authors.forename: Stanislas
authors.initials: S
authors.lastname: Pol
authors.affiliation: AP-HP, Hôpital Henri Mondor, Département de Santé Publique, and Université Paris-Est, Ageing-Thorax-Vessels-Blood Département Hospitalo-Universitaire, Clinical Epidemiology and Aging Unit, Université Paris-Est Créteil, Créteil, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Roudot-Thoraval
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D001424:Bacterial Infections / Q000453:epidemiology; D015992:Body Mass Index; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology* / Q000401:mortality; D002318:Cardiovascular Diseases / Q000453:epidemiology; D003920:Diabetes Mellitus / Q000453:epidemiology; D050171:Dyslipidemias / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D005602:France / Q000453:epidemiology; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D015994:Incidence; D008103:Liver Cirrhosis / Q000150:complications / Q000401:mortality / Q000503:physiopathology*; D008113:Liver Neoplasms / Q000453:epidemiology* / Q000401:mortality; D008297:Male; D024821:Metabolic Syndrome / Q000453:epidemiology; D008875:Middle Aged; D010976:Platelet Count; D011446:Prospective Studies; D011517:Prothrombin Time; D000072230:Sustained Virologic Response; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D000998:Antiviral Agents; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases
keywords: ANRS CirVir; Direct Antivirals; HCV Clearance; Prognosis