TY - JOUR
T1 - Hepatic steatosis, metabolic dysfunction and risk of mortality
T2 - findings from a multinational prospective cohort study
AU - Mayén, Ana-Lucia
AU - Sabra, Mirna
AU - Aglago, Elom K
AU - Perlemuter, Gabriel
AU - Voican, Cosmin
AU - Ramos, Ines
AU - Debras, Charlotte
AU - Blanco, Jessica
AU - Viallon, Vivian
AU - Ferrari, Pietro
AU - Olsen, Anja
AU - Tjønneland, Anne
AU - Langmann, Fie
AU - Dahm, Christina C
AU - Rothwell, Joseph
AU - Laouali, Nasser
AU - Marques, Chloé
AU - Schulze, Matthias B
AU - Katzke, Verena
AU - Kaaks, Rudolf
AU - Palli, Domenico
AU - Macciotta, Alessandra
AU - Panico, Salvatore
AU - Tumino, Rosario
AU - Agnoli, Claudia
AU - Farràs, Marta
AU - Molina-Montes, Esther
AU - Amiano, Pilar
AU - Chirlaque, María-Dolores
AU - Castilla, Jesús
AU - Werner, Mårten
AU - Bodén, Stina
AU - Heath, Alicia K
AU - Tsilidis, Kostas
AU - Aune, Dagfinn
AU - Weiderpass, Elisabete
AU - Freisling, Heinz
AU - Gunter, Marc J
AU - Jenab, Mazda
N1 - © 2024. World Health Organization.
PY - 2024/6/3
Y1 - 2024/6/3
N2 - 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.
AB - 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.
KW - Humans
KW - Male
KW - Female
KW - Middle Aged
KW - Prospective Studies
KW - Metabolic Syndrome/mortality
KW - Non-alcoholic Fatty Liver Disease/mortality
KW - Adult
KW - Aged
KW - Risk Factors
KW - Cohort Studies
KW - Fatty Liver/mortality
KW - Hepatic steatosis
KW - Metabolic syndrome
KW - Mortality
KW - Phenotypic NASH
KW - MAFLD
UR - http://www.scopus.com/inward/record.url?scp=85195008961&partnerID=8YFLogxK
U2 - 10.1186/s12916-024-03366-3
DO - 10.1186/s12916-024-03366-3
M3 - Journal article
C2 - 38825687
SN - 1741-7015
VL - 22
JO - BMC Medicine
JF - BMC Medicine
IS - 1
M1 - 221
ER -