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

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

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.

Publication types

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

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use
  • Coinfection / diagnostic imaging
  • Coinfection / drug therapy
  • Coinfection / mortality*
  • Elasticity Imaging Techniques
  • Female
  • France
  • HIV Infections / diagnostic imaging
  • HIV Infections / drug therapy
  • HIV Infections / mortality*
  • Hepatitis C, Chronic / diagnostic imaging
  • Hepatitis C, Chronic / drug therapy
  • Hepatitis C, Chronic / mortality*
  • Humans
  • Liver / diagnostic imaging*
  • Male
  • Middle Aged
  • Mortality
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Factors
  • Sustained Virologic Response

Substances

  • Antiviral Agents

Grants and funding

The official sponsor of the study is the French national agency for HIV and hepatitis research (ANRS) (LW). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.