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- Title
Hepatic steatosis, metabolic dysfunction and risk of mortality: findings from a multinational prospective cohort study.
- Authors
Mayén, Ana-Lucia; Sabra, Mirna; Aglago, Elom K.; Perlemuter, Gabriel; Voican, Cosmin; Ramos, Ines; Debras, Charlotte; Blanco, Jessica; Viallon, Vivian; Ferrari, Pietro; Olsen, Anja; Tjønneland, Anne; Langmann, Fie; Dahm, Christina C.; Rothwell, Joseph; Laouali, Nasser; Marques, Chloé; Schulze, Matthias B.; Katzke, Verena; Kaaks, Rudolf
- 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.
- Subjects
FATTY liver; NON-alcoholic fatty liver disease; METABOLIC disorders; PROPORTIONAL hazards models; COHORT analysis
- Publication
BMC Medicine, 2024, Vol 22, Issue 1, p1
- ISSN
1741-7015
- Publication type
Article
- DOI
10.1186/s12916-024-03366-3