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

Sarah Shili-Masmoudi (1, 2) , Philippe Sogni (3) , Victor De Ledinghen (4, 5) , Laure Esterle (1, 2) , Marc-Antoine Valantin (6) , Isabelle Poizot-Martin (7) , Anne Simon (6) , Eric Rosenthal (8) , Karine Lacombe (9, 10) , Gilles Pialoux (11) , Olivier Bouchaud (12) , Anne Gervais-Hasenknoff (13) , Cécile Goujard (14)

1 ISPED - Institut de Santé Publique, d'Epidémiologie et de Développement
2 BPH - Bordeaux population health
3 Service d'hépatologie médicale [CHU Cochin]
4 Physiopathologie du cancer du foie
5 Hôpital Haut-Lévêque [CHU Bordeaux]
6 CHU Pitié-Salpêtrière [AP-HP]
7 SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD - Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale
8 Hôpital l'Archet
9 CHU Saint-Antoine [AP-HP]
10 iPLESP - Institut Pierre Louis d'Epidémiologie et de Santé Publique
11 CHU Tenon [AP-HP]
12 Service de maladies infectieuses et tropicales [CHU Avicenne]
13 Services de Maladies Infectieuses et Tropicales [CHU Bichat]
14 GHU Paris-Sud - Laboratoire d'Immunologie [AP-HP Hôpital Kremlin-Bicêtre]

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.

Mots clés: Hepatitis C virus; Death rates; HIV; Alcohol consumption; Metabolic disorders; Drug users; Liver fibrosis; Liver diseases

Domaines: Santé publique et épidémiologie

Sarah Shili-Masmoudi, Philippe Sogni, Victor De Ledinghen, Laure Esterle, Marc-Antoine Valantin, et al.. Increased liver stiffness is associated with mortality in HIV/HCV coinfected subjects: The French nationwide ANRS CO13 HEPAVIH cohort study. PLoS ONE, 2019, 14 (1), pp.e0211286. ⟨10.1371/journal.pone.0211286⟩. ⟨hal-02613071⟩