title: Complications and competing risks of death in compensated viral cirrhosis (ANRS CO12 CirVir prospective cohort).
abstract: Various critical events, liver related or not, occur in patients with compensated cirrhosis, but their respective burden remains to be prospectively assessed. The aim of this prospective cohort study involving 35 French centers was to capture the whole spectrum of complications occurring in compensated viral cirrhosis (VC) using competing risks analyses. Inclusion criteria were: histologically proven cirrhosis resulting from hepatitis C virus (HCV) or hepatitis B virus (HBV); Child-Pugh A; and no previous hepatic complications. The cohort was considered as a multistate disease model, cumulative incidences (CumIs) of events were estimated in a competing risks framework. A total of 1,654 patients were enrolled from 2006 to 2012 (HCV, 1,308; HBV, 315; HCV-HBV, 31). During a median follow-up of 34 months, at least one liver nodule was detected in 271 patients, confirmed as hepatocellular carcinoma (HCC) in 128 (4-year cumI: 10.5%) and cholangiocarcinoma in 3. HCC incidence was higher in HCV (4-year cumI: 11.4% vs. 7.4%; P = 0.05). HCC fulfilled Milan criteria in 79.3%, leading to curative treatment in 70.4%. Liver decompensation occurred more frequently in HCV patients (4-year cumI: 10.8% vs. 3.6%; P = 0.0004). Virological eradication/control was achieved in 34.1% of HCV and 88.6% of HBV patients and was associated with a marked decrease in HCC, decompensation, and bacterial infection incidences. Survival was shorter in HCV patients (4-year cumI: 91.6% vs. 97.2%; P = 0.0002). Death (n = 102; missing data: 6) was attributed to liver disease in 48 (47%; liver cancer: n = 18; miscellaneous, n = 30) and extrahepatic causes in 48 (47%; bacterial infection: n = 13; extrahepatic cancers: n = 10; cardiovascular events: n = 5; miscellaneous, n = 20).
  
  
  CONCLUSIONS
  After 3 years of follow-up, extrahepatic events still explained half of deaths in patients with compensated VC. A strong decrease in complications was linked to virological eradication/control.
authors: AP-HP, Hôpital Jean Verdier, Service d'Hépatologie, Bondy, Université Paris 13, Bobigny et INSERM U1162, Université Paris 5, Paris, France.
authors: Jean-Claude
authors: JC
authors: Trinchet
authors: AP-HP, Hôpital Jean Verdier, Service d'Hépatologie, Bondy, Université Paris 13, Bobigny et INSERM U1162, Université Paris 5, Paris, France.
authors: Valérie
authors: V
authors: Bourcier
authors: AP-HP, Hôpital Saint-Louis, SBIM, Université Paris Diderot, Inserm UMR 1153, Paris, France.
authors: Cendrine
authors: C
authors: Chaffaut
authors: AP-HP, Hôpital Jean Verdier, Service d'Hépatologie, Bondy, Université Paris 13, Bobigny et INSERM U1162, Université Paris 5, Paris, France.
authors: Mohand
authors: M
authors: Ait Ahmed
authors: ANRS (Agence Nationale de Recherche sur le SIDA et les hépatites virales), Paris, France.
authors: Setty
authors: S
authors: Allam
authors: AP-HP, Hôpital Beaujon, Service d'Hépatologie, Clichy, France.
authors: Patrick
authors: P
authors: Marcellin
authors: CHU Pontchaillou, Service d'Hépatologie, Rennes, France.
authors: Dominique
authors: D
authors: Guyader
authors: AP-HP, Hôpital Cochin, Département d'Hépatologie et INSERM U1016, Université Paris Descartes, Paris, France.
authors: Stanislas
authors: S
authors: Pol
authors: Hôpital Saint Eloi, Service d'Hépatologie, Montpellier, France.
authors: Dominique
authors: D
authors: Larrey
authors: Hôpital Haut-lévêque, Service d'Hépatologie, Bordeaux, France.
authors: Victor
authors: V
authors: De Lédinghen
authors: Institut Arnaud Tzanck, Service d'Hépatologie, St Laurent du Var, France.
authors: Denis
authors: D
authors: Ouzan
authors: Hôpital Hôtel Dieu, Service d'Hépatologie, Lyon, France.
authors: Fabien
authors: F
authors: Zoulim
authors: AP-HP, Hôpital Avicenne, Service d'Hépatologie, Bobigny, France.
authors: Dominique
authors: D
authors: Roulot
authors: CHU de Nice, Service d'Hépatologie, et INSERM U1065, Université de Nice-Sophia-Antipolis, Nice, France.
authors: Albert
authors: A
authors: Tran
authors: Hôpital Brabois, Service d'Hépatologie, Vandoeuvre-les-Nancy, France.
authors: Jean-Pierre
authors: JP
authors: Bronowicki
authors: Hôpital Michallon, Service d'Hépatologie, Grenoble, France.
authors: Jean-Pierre
authors: JP
authors: Zarski
authors: Hôpital Charles-Nicolle, Service d'Hépatologie, Rouen, France.
authors: Odile
authors: O
authors: Goria
authors: CHU d'Angers, Service d'Hépatologie, Angers, France.
authors: Paul
authors: P
authors: Calès
authors: Hôpital Purpan, Service d'Hépatologie, Toulouse, France.
authors: Jean-Marie
authors: JM
authors: Péron
authors: CHU Toulouse, Service de Médecine Interne-Pôle Digestif UMR 152, Toulouse, France.
authors: Laurent
authors: L
authors: Alric
authors: Hôpital Saint Joseph, Service d'Hépatologie, Marseille, France.
authors: Marc
authors: M
authors: Bourlière
authors: Hôpital Claude Huriez, Service d'Hépatologie, Lille, France.
authors: Philippe
authors: P
authors: Mathurin
authors: Hôpital St André, Service d'Hépatologie, Bordeaux, France.
authors: Jean-Frédéric
authors: JF
authors: Blanc
authors: Hôpital Hôtel Dieu, Service d'Hépatologie, Clermont-Ferrand, France.
authors: Armand
authors: A
authors: Abergel
authors: AP-HP, Hôpital Saint-Antoine, Service d'Hépatologie, Paris, France.
authors: Lawrence
authors: L
authors: Serfaty
authors: AP-HP, Hôpital Henri Mondor, Service d'Hépatologie, Créteil, France.
authors: Ariane
authors: A
authors: Mallat
authors: AP-HP, Hôpital Tenon, Service d'Hépatologie, Paris, France.
authors: Jean-Didier
authors: JD
authors: Grangé
authors: AP-HP, CHU Kremlin-Bicêtre, Service d'Hépatologie, Le Kremlin-Bicêtre, France.
authors: Catherine
authors: C
authors: Buffet
authors: Hôpital Trousseau, Service d'Hépatologie, Tours, France.
authors: Yannick
authors: Y
authors: Bacq
authors: Hôpital d'Aix-En-Provence, Service d'Hépatologie, Aix-En-Provence, France.
authors: Claire
authors: C
authors: Wartelle
authors: Hôpital de la Côte de Nacre, Service d'Hépatologie, Caen, France.
authors: Thông
authors: T
authors: Dao
authors: AP-HP, Groupe Hospitalier de La Pitié-Salpêtrière, Service d'Hépatologie, Paris, France.
authors: Yves
authors: Y
authors: Benhamou
authors: CHU Le Mans, Service d'Hépatologie, Le Mans, France.
authors: Christophe
authors: C
authors: Pilette
authors: CHU de Poitiers, Service d'Hépatologie, Poitiers, France.
authors: Christine
authors: C
authors: Silvain
authors: Institut Mutualiste Montsouris, Service d'Hépatologie, Paris, France.
authors: Christos
authors: C
authors: Christidis
authors: Hôpital Amiens Nord, Service d'Hépatologie, Amiens, France.
authors: Dominique
authors: D
authors: Capron
authors: Hôpital Robert Debré, Service d'Hépatologie, Reims, France.
authors: Gérard
authors: G
authors: Thiefin
authors: Hôpital Foch, Service d'Hépatologie, Suresnes, France.
authors: Sophie
authors: S
authors: Hillaire
authors: Hôpital Jean Minjoz, Service d'Hépatologie, Besançon, France.
authors: Vincent
authors: V
authors: Di Martino
authors: AP-HP, Hôpital Jean Verdier, Service d'Hépatologie, Bondy, Université Paris 13, Bobigny et INSERM U1162, Université Paris 5, Paris, France.
authors: Pierre
authors: P
authors: Nahon
authors: AP-HP, Hôpital Saint-Louis, SBIM, Université Paris Diderot, Inserm UMR 1153, Paris, France.
authors: Sylvie
authors: S
authors: Chevret
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D006528:Carcinoma, Hepatocellular / Q000401:mortality / Q000503:physiopathology / Q000821:virology*; D002423:Cause of Death; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005602:France; D006509:Hepatitis B / Q000150:complications / Q000473:pathology; D006526:Hepatitis C / Q000150:complications / Q000473:pathology; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications / Q000401:mortality* / Q000821:virology*; D017093:Liver Failure / Q000401:mortality / Q000473:pathology / Q000821:virology; D008113:Liver Neoplasms / Q000401:mortality / Q000473:pathology / Q000821:virology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D016019:Survival Analysis