Hepatic steatosis, metabolic dysfunction and risk of mortality: findings from a multinational prospective cohort study

BMC Med. 2024 Jun 3;22(1):221. doi: 10.1186/s12916-024-03366-3.

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) are implicated in the aetiology of non-communicable diseases. Our study aimed to evaluate associations between NAFLD and MetS with overall and cause-specific mortality.

Methods: We used dietary, lifestyle, anthropometric and metabolic biomarker data from a random subsample of 15,784 EPIC cohort participants. NAFLD was assessed using the fatty liver index (FLI) and MetS using the revised definition. Indices for metabolic dysfunction-associated fatty liver disease (MAFLD) were calculated. The individual associations of these indices with overall and cause-specific mortality were assessed using multivariable Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (95%CIs). As a subobjective, risk associations with adaptations of new classifications of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic and alcohol-related liver disease (MetALD) were also assessed.

Results: Among the 15,784 sub-cohort participants, a total of 1997 deaths occurred (835 due to cancer, 520 to CVD, 642 to other causes) over a median 15.6 (IQR, 12.3-17.1) years of follow-up. Compared to an FLI < 30, FLI ≥ 60 was associated with increased risks of overall mortality (HR = 1.44, 95%CI = 1.27-1.63), and deaths from cancer (HR = 1.32, 95%CI = 1.09-1.60), CVD (HR = 2.06, 95% CI = 1.61-2.63) or other causes (HR = 1.21, 95%CI = 0.97-1.51). Mortality risk associations were also elevated for individuals with MAFLD compared to those without. Individuals with MetS were at increased risk of all mortality endpoints, except cancer-specific mortality. MASLD and MetALD were associated with higher risk of overall mortality.

Conclusions: Our findings based on a prospective cohort suggest that individuals with hepatic steatosis or metabolic dysfunction have a higher overall and cause-specific mortality risk.

Keywords: Hepatic steatosis; MAFLD; Metabolic syndrome; Mortality; Phenotypic NASH.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Cohort Studies
  • Fatty Liver / mortality
  • Female
  • Humans
  • Male
  • Metabolic Syndrome* / mortality
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease* / mortality
  • Prospective Studies
  • Risk Factors