• Ana-Lucia Mayén, Mirna Sabra, Elom K Aglago, Gabriel Perlemuter, Cosmin Voican, Ines Ramos, Charlotte Debras, Jessica Blanco, Vivian Viallon, Pietro Ferrari, Anja Olsen, Anne Tjønneland, Fie Langmann, Christina C Dahm, Joseph Rothwell, Nasser Laouali, Chloé Marques, Matthias B Schulze, Verena Katzke, Rudolf Kaaks, Domenico Palli, Alessandra Macciotta, Salvatore Panico, Rosario Tumino, Claudia Agnoli, Marta Farràs, Esther Molina-Montes, Pilar Amiano, María-Dolores Chirlaque, Jesús Castilla, Mårten Werner, Stina Bodén, Alicia K Heath, Kostas Tsilidis, Dagfinn Aune, Elisabete Weiderpass, Heinz Freisling, Marc J Gunter, and Mazda Jenab.
• Nutrition and Metabolism Branch, International Agency for Research On Cancer (IARC-WHO), 25 Avenue Tony Garnier, Lyon, 69007, France.
• Bmc Med. 2024 Jun 3; 22 (1): 221221.

BackgroundNon-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.MethodsWe 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.ResultsAmong 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.ConclusionsOur findings based on a prospective cohort suggest that individuals with hepatic steatosis or metabolic dysfunction have a higher overall and cause-specific mortality risk.© 2024. World Health Organization.

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