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PLoS One. 2019 Jan 25;14(1):e0211286. doi: 10.1371/journal.pone.0211286. eCollection 2019.

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

Author information

1
Univ Bordeaux, ISPED, Inserm Bordeaux Population Health, team MORPH3EUS, UMR 1219, CIC-EC 1401, Bordeaux, France.
2
Centre Hospitalier Universitaire de Bordeaux, Hôpital Haut-Lévèque, Service d'Hépatologie, Bordeaux, France.
3
Assistance Publique des Hôpitaux de Paris, Hôpital Cochin, Service d'Hépatologie, Paris, France.
4
INSERM U-1223 -Institut Pasteur, Paris, France.
5
Université Paris Descartes, Paris, France.
6
Univ Bordeaux, Inserm, UMR 1053, Bordeaux, France.
7
Assistance Publique des Hôpitaux de Paris, Hôpital Pitié-Salpétrière, Service Maladies infectieuses et tropicales, Paris, France.
8
Aix Marseille Univ, APHM Sainte-Marguerite, Service d'Immuno-hématologie clinique, Marseille, France.
9
Inserm U912 (SESSTIM) Marseille, France.
10
Assistance Publique des Hôpitaux de Paris, Hôpital Pitié-Salpétrière, Département de Médecine Interne et Immunologie Clinique, Paris, France.
11
Centre Hospitalier Universitaire de Nice, Service de Médecine Interne et Cancérologie, Hôpital l'Archet, Nice, France.
12
Université de Nice-Sophia Antipolis, Nice, France.
13
Assistance Publique des Hôpitaux de Paris, Hôpital Saint-Antoine, Service Maladies infectieuses et tropicales, Paris, France.
14
UMPC (Université Pierre et Marie Curie), UMR S1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France.
15
Assistance Publique des Hôpitaux de Paris, Hôpital Tenon, Service Maladies infectieuses et tropicales, Paris, France.
16
Assistance Publique des Hôpitaux de Paris, Hôpital Avicenne, Service Maladies infectieuses et tropicales, Bobigny, France.
17
Université Paris 13 Nord, Bobigny, France.
18
Assistance Publique des Hôpitaux de Paris, Hôpital Bichat Claude Bernard, Service des maladies infectieuses et tropicales, Paris, France.
19
Assistance Publique des Hôpitaux de Paris, Hôpital Bicêtre, Hôpitaux universitaires Paris Sud, Service Médecine interne et Immunologie clinique, Le Kremlin-Bicêtre, France.
20
Université Paris Sud, Le Kremlin-Bicêtre, France.
21
Centre Hospitalier Universitaire de Dijon, Département d'Infectiologie, Dijon, France.
22
Université de Bourgogne, Dijon, France.
23
Hôpital Foch, unité VIH, Suresnes, France.
24
Assistance Publique des Hôpitaux de Paris, Hôpital Henri Mondor, Service Immunologie clinique et maladies infectieuses, Immunologie clinique, Créteil, France.
25
Centre Hospitalier Universitaire de Nantes, Service Maladies infectieuses et tropicales, Nantes, France.
26
Centre Hospitalier Universitaire de Toulouse, Hôpital Purpan, Médecine interne, Toulouse, France.
27
Université Toulouse III, Paul Sabatier, Toulouse, France.
28
Centre Hospitalier Universitaire de Reims, Service de médecine interne, maladies infectieuses et immunologie clinique, Reims, France.
29
Université de Reims, Champagne-Ardenne, Reims, France.
30
Assistance Publique des Hôpitaux de Paris, Hôpital Saint-Louis, Service Maladies infectieuses et tropicales, Paris, France.
31
Centre Hospitalier Universitaire de Toulouse, Hôpital Purpan, Maladies infectieuses et tropicales, Toulouse, France.
32
Service des Maladies Infectieuses et Tropicales, CHU Lyon, Hôpital de la Croix Rousse, Lyon, France.
33
Assistance Publique des Hôpitaux de Paris, Hôpital Bicêtre, Hôpitaux universitaires Paris Sud, Service Maladies infectieuses et tropicales, Le Kremlin-Bicêtre, France.
34
APHP-Hôpital Necker-Enfants malades, Service de Maladies Infectieuses et Tropicales, Paris, France.
35
Centre d'Infectiologie Necker-Pasteur, Paris, France.
36
Centre Hospitalier de Perpignan, Service Maladies infectieuses et tropicales, Perpignan, France.
37
Centre Hospitalier Universitaire de Bordeaux, Service Maladies infectieuses et tropicales Bordeaux, Hôpital Pellegrin, Bordeaux, France.
38
Centre Hospitalier Universitaire de Bordeaux, Service de médecine interne, hôpital Saint-André, Bordeaux, France.
39
Centre Hospitalier Universitaire de Bordeaux, Pôle de Santé Publique, Bordeaux, France.
40
Assistance Publique des Hôpitaux de Paris, Hôpital Cochin, Service Maladies infectieuses et tropicales, Paris, France.

Abstract

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.

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