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

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

Ana-Lucia Mayén  1 , Mirna Sabra  1 , Elom K Aglago  2 , Gabriel Perlemuter  3   4   5 , Cosmin Voican  3   4   5 , Ines Ramos  1 , Charlotte Debras  1 , Jessica Blanco  1 , Vivian Viallon  1 , Pietro Ferrari  1 , Anja Olsen  6   7 , Anne Tjønneland  6   7 , Fie Langmann  7 , Christina C Dahm  7 , Joseph Rothwell  8 , Nasser Laouali  8 , Chloé Marques  8 , Matthias B Schulze  9 , Verena Katzke  10 , Rudolf Kaaks  10 , Domenico Palli  11 , Alessandra Macciotta  12 , Salvatore Panico  13 , Rosario Tumino  14 , Claudia Agnoli  15 , Marta Farràs  16 , Esther Molina-Montes  17   18   19   20 , Pilar Amiano  18   21   22 , María-Dolores Chirlaque  18   23 , Jesús Castilla  18   24 , Mårten Werner  25 , Stina Bodén  26 , Alicia K Heath  2 , Kostas Tsilidis  2 , Dagfinn Aune  2   27   28 , Elisabete Weiderpass  29 , Heinz Freisling  1 , Marc J Gunter  2 , Mazda Jenab  30
Affiliations
Multicenter Study

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

Ana-Lucia Mayén et al. BMC Med. .

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.

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Conflict of interest statement

The authors declare that they have no competing interests.

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