Complications and competing risks of death in compensated viral cirrhosis (ANRS CO12 CirVir prospective cohort)

Jean-Claude Trinchet (1) , Valérie Bourcier (1) , Cendrine Chaffaut (2, 3) , Mohand Ait Ahmed (1) , Setty Allam (4) , Patrick Marcellin (5, 6) , Dominique Guyader (7, 8) , Stanislas Pol (9, 10) , Dominique Larrey (11, 12, 13) , Victor de Lédinghen (14) , Denis Ouzan , Fabien Zoulim (15, 16, 17) , Dominique Roulot (18) , Albert Tran (19) , Jean-Pierre Bronowicki (20, 21) , Jean-Pierre Zarski (22) , Odile Goria (23) , Paul Calès (24) , Jean-Marie Peron (25) , Laurent Alric (26, 25) , Marc Bourlière (27) , Philippe Mathurin (28) , Jean-Frederic Blanc (29) , Armand Abergel (30, 31) , Lawrence Serfaty (32) , Ariane Mallat (33, 34) , Jean-Didier Grangé (35) , Catherine Buffet (36) , Yannick Bacq (37) , Claire Wartelle , Thong Dao (38, 39) , Yves Benhamou (40) , Christophe Pilette (41) , Christine Silvain (42) , Christos Christidis (43) , Dominique Capron (32) , Gérard Thiefin (44) , Sophie Hillaire (45) , Vincent Di Martino (46) , Pierre Nahon (47, 1) , Sylvie Chevret (48, 3)

1 Hôpital Jean Verdier [AP-HP]
2 AP-HP - Hopital Saint-Louis [AP-HP]
3 SBIM - Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA)
4 ANRS - Agence Nationale de Recherches sur le Sida et les Hépatites Virales
5 CRI (UMR_S_1149 / ERL_8252 / U1149) - Centre de recherche sur l'Inflammation
6 Service d’Hépatologie [Hôpital Beaujon]
7 Foie, métabolismes et cancer
8 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
9 IC UM3 (UMR 8104 / U1016) - Institut Cochin
10 Département d'hépatologie [CHU Cochin]
11 Cellules souches normales et cancéreuses
12 Département d'Hépato-Gastroentérologie et de Transplantation Hépatique [CHU Saint-Eloi]
13 Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB)
14 Hôpital Haut-Lévêque [CHU Bordeaux]
15 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
16 HCL - Hospices Civils de Lyon
17 Service d'Hépatologie et de Gastroentérologie [Lyon]
18 Service de Gastro-entérologie [Avicenne]
19 C3M - Centre méditerranéen de médecine moléculaire
20 Service d'Hépato-gastro-entérologie [CHRU Nancy]
21 NGERE - Nutrition-Génétique et Exposition aux Risques Environnementaux
22 Département d'hépato-gastroentérologie
23 CHU Rouen
24 HIFIH - Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques
25 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
26 PHARMA-DEV - Pharmacochimie et Biologie pour le Développement
27 Service d'hépatologie et de gastroentérologie [Hôpital Saint-Joseph - Marseille]
28 Hôpital Claude Huriez [Lille]
29 Hôpital Saint-André
30 CHU Estaing [Clermont-Ferrand]
31 Service d'Hépatologie Gastro-entérologie [CHU Clermont-Ferrand]
32 CHU Saint-Antoine [AP-HP]
33 IMRB - Institut Mondor de Recherche Biomédicale
34 Service d'hépato-gastro-entérologie [APHP Henri Mondor]
35 CHU Tenon [AP-HP]
36 Service d'hépato-gastro-entérologie
37 CHU Trousseau [APHP]
38 Service d'Hépato-Gastro-Enterologie et Nutrition [CHU Caen]
39 COMETE - Mobilités : Attention, Orientation et Chronobiologie
40 CHU Pitié-Salpêtrière [AP-HP]
41 Centre Hospitalier Le Mans (CH Le Mans)
42 Hôpital de la Milétrie
43 IMM - Institut mutualiste Monsouris
44 IMM - Institut Mutualiste de Montsouris
45 Hôpital Foch [Suresnes]
46 Hôpital JeanMinjoz
47 CRB3 - Centre de recherche biomédicale Bichat-Beaujon
48 Biostatistique et épidemiologie clinique

Unlabelled - 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). Conclusion - 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.

Mots clés: Adult; Analysis of Variance; Carcinoma; Hepatocellular / mortality; Hepatocellular / physiopathology; Hepatocellular / virology; Cause of Death; Cohort Studies; Disease Progression; Female; France; Hepatitis B / complications; Hepatitis B / pathology; Hepatitis C / complications; Hepatitis C / pathology; Humans; Liver Cirrhosis / complications; Liver Cirrhosis / mortality; Liver Cirrhosis / virology; Liver Failure / mortality; Liver Failure / pathology; Liver Failure / virology; Liver Neoplasms / mortality; Liver Neoplasms / pathology; Liver Neoplasms / virology; Longitudinal Studies; Male; Middle Aged; Multivariate Analysis; Predictive Value of Tests; Proportional Hazards Models; Prospective Studies; Risk Assessment; Survival Analysis

Domaines: Sciences du Vivant [q-bio]

Jean-Claude Trinchet, Valérie Bourcier, Cendrine Chaffaut, Mohand Ait Ahmed, Setty Allam, et al.. Complications and competing risks of death in compensated viral cirrhosis (ANRS CO12 CirVir prospective cohort). Hepatology, 2015, 62 (3), pp.737-750. ⟨10.1002/hep.27743⟩. ⟨hal-01201948⟩