Increased liver stiffness is associated with mortality in HIV/HCV coinfected subjects: The French nationwide ANRS CO13 HEPAVIH cohort study.


Journal

PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081

Informations de publication

Date de publication:
2019
Historique:
received: 10 10 2018
accepted: 10 01 2019
entrez: 26 1 2019
pubmed: 27 1 2019
medline: 29 10 2019
Statut: epublish

Résumé

The association between liver stiffness measurements (LSM) and mortality has not been fully described. In particular the effect of LSM on all-cause mortality taking sustained virological response (SVR) into account needs further study. HIV/HCV participants in the French nation-wide, prospective, multicenter ANRS CO13 HEPAVIH cohort, with ≥1 LSM by FibroScan (FS) and a detectable HCV RNA when the first valid FS was performed were included. Cox proportional hazards models with delayed entry were performed to determine factors associated with all-cause mortality. LSM and SVR were considered as time dependent covariates. 1,062 patients were included from 2005 to 2015 (69.8% men, median age 45.7 years (IQR 42.4-49.1)). 21.7% had baseline LSM >12.5 kPa. Median follow-up was 4.9 years (IQR 3.2-6.1). 727 (68.5%) were ever treated for HCV: 189 of them (26.0%) achieved SVR. 76 deaths were observed (26 liver-related, 10 HIV-related, 29 non-liver-non-HIV-related, 11 of unknown cause). At the age of 50, the mortality rate was 4.5% for patients with LSM ≤12.5 kPa and 10.8% for patients with LSM >12.5 kPa. LSM >12.5 kPa (adjusted Hazard Ratio [aHR] = 3.35 [2.06; 5.45], p<0.0001), history of HCV treatment (aHR = 0.53 [0.32; 0.90], p = 0.01) and smoking (past (aHR = 5.69 [1.56; 20.78]) and current (3.22 [0.93; 11.09]) versus never, p = 0.01) were associated with all-cause mortality independently of SVR, age, sex, alcohol use and metabolic disorders. Any LSM >12.5 kPa was strongly associated with all-cause mortality independently of SVR and other important covariates. Our results suggest that close follow-up of these patients should remain a priority even after achieving SVR.

Sections du résumé

BACKGROUND
The association between liver stiffness measurements (LSM) and mortality has not been fully described. In particular the effect of LSM on all-cause mortality taking sustained virological response (SVR) into account needs further study.
METHODS
HIV/HCV participants in the French nation-wide, prospective, multicenter ANRS CO13 HEPAVIH cohort, with ≥1 LSM by FibroScan (FS) and a detectable HCV RNA when the first valid FS was performed were included. Cox proportional hazards models with delayed entry were performed to determine factors associated with all-cause mortality. LSM and SVR were considered as time dependent covariates.
RESULTS
1,062 patients were included from 2005 to 2015 (69.8% men, median age 45.7 years (IQR 42.4-49.1)). 21.7% had baseline LSM >12.5 kPa. Median follow-up was 4.9 years (IQR 3.2-6.1). 727 (68.5%) were ever treated for HCV: 189 of them (26.0%) achieved SVR. 76 deaths were observed (26 liver-related, 10 HIV-related, 29 non-liver-non-HIV-related, 11 of unknown cause). At the age of 50, the mortality rate was 4.5% for patients with LSM ≤12.5 kPa and 10.8% for patients with LSM >12.5 kPa. LSM >12.5 kPa (adjusted Hazard Ratio [aHR] = 3.35 [2.06; 5.45], p<0.0001), history of HCV treatment (aHR = 0.53 [0.32; 0.90], p = 0.01) and smoking (past (aHR = 5.69 [1.56; 20.78]) and current (3.22 [0.93; 11.09]) versus never, p = 0.01) were associated with all-cause mortality independently of SVR, age, sex, alcohol use and metabolic disorders.
CONCLUSION
Any LSM >12.5 kPa was strongly associated with all-cause mortality independently of SVR and other important covariates. Our results suggest that close follow-up of these patients should remain a priority even after achieving SVR.

Identifiants

pubmed: 30682180
doi: 10.1371/journal.pone.0211286
pii: PONE-D-18-29412
pmc: PMC6347250
doi:

Substances chimiques

Antiviral Agents 0

Types de publication

Journal Article Multicenter Study Observational Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e0211286

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

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Auteurs

Sarah Shili-Masmoudi (S)

Univ Bordeaux, ISPED, Inserm Bordeaux Population Health, team MORPH3EUS, UMR 1219, CIC-EC 1401, Bordeaux, France.
Centre Hospitalier Universitaire de Bordeaux, Hôpital Haut-Lévèque, Service d'Hépatologie, Bordeaux, France.

Philippe Sogni (P)

Assistance Publique des Hôpitaux de Paris, Hôpital Cochin, Service d'Hépatologie, Paris, France.
INSERM U-1223 -Institut Pasteur, Paris, France.
Université Paris Descartes, Paris, France.

Victor de Ledinghen (V)

Centre Hospitalier Universitaire de Bordeaux, Hôpital Haut-Lévèque, Service d'Hépatologie, Bordeaux, France.
Univ Bordeaux, Inserm, UMR 1053, Bordeaux, France.

Laure Esterle (L)

Univ Bordeaux, ISPED, Inserm Bordeaux Population Health, team MORPH3EUS, UMR 1219, CIC-EC 1401, Bordeaux, France.

Marc-Antoine Valantin (MA)

Assistance Publique des Hôpitaux de Paris, Hôpital Pitié-Salpétrière, Service Maladies infectieuses et tropicales, Paris, France.

Isabelle Poizot-Martin (I)

Aix Marseille Univ, APHM Sainte-Marguerite, Service d'Immuno-hématologie clinique, Marseille, France.
Inserm U912 (SESSTIM) Marseille, France.

Anne Simon (A)

Assistance Publique des Hôpitaux de Paris, Hôpital Pitié-Salpétrière, Département de Médecine Interne et Immunologie Clinique, Paris, France.

Eric Rosenthal (E)

Centre Hospitalier Universitaire de Nice, Service de Médecine Interne et Cancérologie, Hôpital l'Archet, Nice, France.
Université de Nice-Sophia Antipolis, Nice, France.

Karine Lacombe (K)

Assistance Publique des Hôpitaux de Paris, Hôpital Saint-Antoine, Service Maladies infectieuses et tropicales, Paris, France.
UMPC (Université Pierre et Marie Curie), UMR S1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France.

Gilles Pialoux (G)

Assistance Publique des Hôpitaux de Paris, Hôpital Tenon, Service Maladies infectieuses et tropicales, Paris, France.

Olivier Bouchaud (O)

Assistance Publique des Hôpitaux de Paris, Hôpital Avicenne, Service Maladies infectieuses et tropicales, Bobigny, France.
Université Paris 13 Nord, Bobigny, France.

Anne Gervais-Hasenknoff (A)

Assistance Publique des Hôpitaux de Paris, Hôpital Bichat Claude Bernard, Service des maladies infectieuses et tropicales, Paris, France.

Cécile Goujard (C)

Assistance Publique des Hôpitaux de Paris, Hôpital Bicêtre, Hôpitaux universitaires Paris Sud, Service Médecine interne et Immunologie clinique, Le Kremlin-Bicêtre, France.
Université Paris Sud, Le Kremlin-Bicêtre, France.

Lionel Piroth (L)

Centre Hospitalier Universitaire de Dijon, Département d'Infectiologie, Dijon, France.
Université de Bourgogne, Dijon, France.

David Zucman (D)

Hôpital Foch, unité VIH, Suresnes, France.

Stéphanie Dominguez (S)

Assistance Publique des Hôpitaux de Paris, Hôpital Henri Mondor, Service Immunologie clinique et maladies infectieuses, Immunologie clinique, Créteil, France.

François Raffi (F)

Centre Hospitalier Universitaire de Nantes, Service Maladies infectieuses et tropicales, Nantes, France.

Laurent Alric (L)

Centre Hospitalier Universitaire de Toulouse, Hôpital Purpan, Médecine interne, Toulouse, France.
Université Toulouse III, Paul Sabatier, Toulouse, France.

Firouzé Bani-Sadr (F)

Centre Hospitalier Universitaire de Reims, Service de médecine interne, maladies infectieuses et immunologie clinique, Reims, France.
Université de Reims, Champagne-Ardenne, Reims, France.

Caroline Lascoux-Combe (C)

Assistance Publique des Hôpitaux de Paris, Hôpital Saint-Louis, Service Maladies infectieuses et tropicales, Paris, France.

Daniel Garipuy (D)

Centre Hospitalier Universitaire de Toulouse, Hôpital Purpan, Maladies infectieuses et tropicales, Toulouse, France.

Patrick Miailhes (P)

Service des Maladies Infectieuses et Tropicales, CHU Lyon, Hôpital de la Croix Rousse, Lyon, France.

Daniel Vittecoq (D)

Université Paris Sud, Le Kremlin-Bicêtre, France.
Assistance Publique des Hôpitaux de Paris, Hôpital Bicêtre, Hôpitaux universitaires Paris Sud, Service Maladies infectieuses et tropicales, Le Kremlin-Bicêtre, France.

Claudine Duvivier (C)

APHP-Hôpital Necker-Enfants malades, Service de Maladies Infectieuses et Tropicales, Paris, France.
Centre d'Infectiologie Necker-Pasteur, Paris, France.

Hugues Aumaître (H)

Centre Hospitalier de Perpignan, Service Maladies infectieuses et tropicales, Perpignan, France.

Didier Neau (D)

Centre Hospitalier Universitaire de Bordeaux, Service Maladies infectieuses et tropicales Bordeaux, Hôpital Pellegrin, Bordeaux, France.

Philippe Morlat (P)

Univ Bordeaux, ISPED, Inserm Bordeaux Population Health, team MORPH3EUS, UMR 1219, CIC-EC 1401, Bordeaux, France.
Centre Hospitalier Universitaire de Bordeaux, Service de médecine interne, hôpital Saint-André, Bordeaux, France.

François Dabis (F)

Univ Bordeaux, ISPED, Inserm Bordeaux Population Health, team MORPH3EUS, UMR 1219, CIC-EC 1401, Bordeaux, France.
Centre Hospitalier Universitaire de Bordeaux, Pôle de Santé Publique, Bordeaux, France.

Dominique Salmon (D)

Université Paris Descartes, Paris, France.
Assistance Publique des Hôpitaux de Paris, Hôpital Cochin, Service Maladies infectieuses et tropicales, Paris, France.

Linda Wittkop (L)

Univ Bordeaux, ISPED, Inserm Bordeaux Population Health, team MORPH3EUS, UMR 1219, CIC-EC 1401, Bordeaux, France.
Centre Hospitalier Universitaire de Bordeaux, Pôle de Santé Publique, Bordeaux, France.

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