BMC Medicine (Jun 2024)
Hepatic steatosis, metabolic dysfunction and risk of mortality: findings from a multinational prospective cohort study
- 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,
- Mazda Jenab
Affiliations
- Ana-Lucia Mayén
- Nutrition and Metabolism Branch, International Agency for Research On Cancer (IARC-WHO)
- Mirna Sabra
- Nutrition and Metabolism Branch, International Agency for Research On Cancer (IARC-WHO)
- Elom K. Aglago
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London
- Gabriel Perlemuter
- INSERM U996, Intestinal Microbiota, Macrophages and Liver Inflammation, DHU HepatinovLabex LERMIT
- Cosmin Voican
- INSERM U996, Intestinal Microbiota, Macrophages and Liver Inflammation, DHU HepatinovLabex LERMIT
- Ines Ramos
- Nutrition and Metabolism Branch, International Agency for Research On Cancer (IARC-WHO)
- Charlotte Debras
- Nutrition and Metabolism Branch, International Agency for Research On Cancer (IARC-WHO)
- Jessica Blanco
- Nutrition and Metabolism Branch, International Agency for Research On Cancer (IARC-WHO)
- Vivian Viallon
- Nutrition and Metabolism Branch, International Agency for Research On Cancer (IARC-WHO)
- Pietro Ferrari
- Nutrition and Metabolism Branch, International Agency for Research On Cancer (IARC-WHO)
- Anja Olsen
- Danish Cancer Society Research Center, Diet, Cancer and Health
- Anne Tjønneland
- Danish Cancer Society Research Center, Diet, Cancer and Health
- Fie Langmann
- Department of Public Health, Aarhus University
- Christina C. Dahm
- Department of Public Health, Aarhus University
- Joseph Rothwell
- Université Paris-Saclay, UVSQ, Inserm “Exposome and Heredity” Team, CESP U1018, Gustave Roussy
- Nasser Laouali
- Université Paris-Saclay, UVSQ, Inserm “Exposome and Heredity” Team, CESP U1018, Gustave Roussy
- Chloé Marques
- Université Paris-Saclay, UVSQ, Inserm “Exposome and Heredity” Team, CESP U1018, Gustave Roussy
- Matthias B. Schulze
- Dept. of Molecular Epidemiology, German Institute of Human Nutrition
- Verena Katzke
- Department of Cancer Epidemiology, German Cancer Research Center (DKFZ)
- Rudolf Kaaks
- Department of Cancer Epidemiology, German Cancer Research Center (DKFZ)
- Domenico Palli
- Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network (ISPRO)
- Alessandra Macciotta
- Department of Clinical and Biological Sciences, Centre for Biostatistics, Epidemiology, and Public Health (C-BEPH), University of Turin
- Salvatore Panico
- Dipartimento Di Medicina Clinica E Chirurgia, Federico II University
- Rosario Tumino
- Hyblean Association for Epidemiological Research, AIRE-ONLUS Ragusa
- Claudia Agnoli
- Department of Research Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale Dei Tumori
- Marta Farràs
- Unit of Nutrition and Cancer, Epidemiology Research Program, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL)
- Esther Molina-Montes
- Department of Nutrition and Food Science, Campus of Cartuja, University of Granada
- Pilar Amiano
- Spanish Consortium for Research On Epidemiology and Public Health (CIBERESP), Instituto de Salud Carlos III
- María-Dolores Chirlaque
- Spanish Consortium for Research On Epidemiology and Public Health (CIBERESP), Instituto de Salud Carlos III
- Jesús Castilla
- Spanish Consortium for Research On Epidemiology and Public Health (CIBERESP), Instituto de Salud Carlos III
- Mårten Werner
- Department of Public Health and Clinical Medicine, Medicine, Umeå University
- Stina Bodén
- Department of Clinical Sciences, Pediatrics, Umeå University
- Alicia K. Heath
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London
- Kostas Tsilidis
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London
- Dagfinn Aune
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London
- Elisabete Weiderpass
- Office of the Director, International Agency for Research On Cancer (IARC-WHO)
- Heinz Freisling
- Nutrition and Metabolism Branch, International Agency for Research On Cancer (IARC-WHO)
- Marc J. Gunter
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London
- Mazda Jenab
- Nutrition and Metabolism Branch, International Agency for Research On Cancer (IARC-WHO)
- DOI
- https://doi.org/10.1186/s12916-024-03366-3
- Journal volume & issue
-
Vol. 22,
no. 1
pp. 1 – 14
Abstract
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
