The relationships between MASLD, extrahepatic multimorbidity and all-cause mortality in UK Biobank cohort
File(s)
Published version (corrected proof)
Author(s)
Type
Journal Article
Abstract
Context
Metabolic dysfunction–associated steatotic liver disease (MASLD) affects one third of the world's population, but its associations with extrahepatic multimorbidity and mortality remain unclear.
Objective
This study aimed to estimate the impact of MASLD, with and without multimorbidity, on all-cause mortality.
Methods
We analyzed data from the UK Biobank. MASLD was identified as a fatty liver index ≥60 and presence of cardiometabolic risk factors. Multimorbidity was defined as ≥2 of the long-term conditions (LTCs) in a prespecified list of 47 extrahepatic conditions. Hazard ratios (HRs) from adjusted Cox models quantified the association between MASLD, multimorbidity and all-cause mortality.
Results
Of the 438 840 participants, 131 020 (29.9%) had MASLD at baseline. The participants with MASLD at baseline had a higher prevalence of multimorbidity than those without (21.3% vs 14.4%). In addition to cardiometabolic risk factors, MASLD was strongly associated with several LTCs, particularly metabolic, cardiovascular, cancers, kidney, mental/behavioral, and respiratory diseases. During a median follow-up of 13 years, MASLD was associated with higher mortality (HR 1.16; 95% CI 1.13, 1.19), with stronger associations in females and in those with low LTC counts (≤3 LTCs). Each additional LTC at baseline was associated with 30% and 38% higher mortality in MASLD (HR 1.30; 1.29, 1.32) and non-MASLD (HR 1.38; 1.37, 1.40) populations, respectively. Among the 47 LTCs, 16 were associated with increased mortality in people with MASLD.
Conclusion
Those with MASLD exhibited a higher prevalence of extrahepatic multimorbidity and a 16% higher rate of mortality than those without, underscoring the impact of liver steatosis on mortality and highlighting the need to target LTCs to improve outcomes and reduce health care burdens.
Metabolic dysfunction–associated steatotic liver disease (MASLD) affects one third of the world's population, but its associations with extrahepatic multimorbidity and mortality remain unclear.
Objective
This study aimed to estimate the impact of MASLD, with and without multimorbidity, on all-cause mortality.
Methods
We analyzed data from the UK Biobank. MASLD was identified as a fatty liver index ≥60 and presence of cardiometabolic risk factors. Multimorbidity was defined as ≥2 of the long-term conditions (LTCs) in a prespecified list of 47 extrahepatic conditions. Hazard ratios (HRs) from adjusted Cox models quantified the association between MASLD, multimorbidity and all-cause mortality.
Results
Of the 438 840 participants, 131 020 (29.9%) had MASLD at baseline. The participants with MASLD at baseline had a higher prevalence of multimorbidity than those without (21.3% vs 14.4%). In addition to cardiometabolic risk factors, MASLD was strongly associated with several LTCs, particularly metabolic, cardiovascular, cancers, kidney, mental/behavioral, and respiratory diseases. During a median follow-up of 13 years, MASLD was associated with higher mortality (HR 1.16; 95% CI 1.13, 1.19), with stronger associations in females and in those with low LTC counts (≤3 LTCs). Each additional LTC at baseline was associated with 30% and 38% higher mortality in MASLD (HR 1.30; 1.29, 1.32) and non-MASLD (HR 1.38; 1.37, 1.40) populations, respectively. Among the 47 LTCs, 16 were associated with increased mortality in people with MASLD.
Conclusion
Those with MASLD exhibited a higher prevalence of extrahepatic multimorbidity and a 16% higher rate of mortality than those without, underscoring the impact of liver steatosis on mortality and highlighting the need to target LTCs to improve outcomes and reduce health care burdens.
Date Issued
2025-01-01
Date Acceptance
2025-06-09
Citation
Journal of Clinical Endocrinology and Metabolism, 2025, 111 (1), pp.e58-e69
ISSN
0021-972X
Publisher
Oxford University Press
Start Page
e58
End Page
e69
Journal / Book Title
Journal of Clinical Endocrinology and Metabolism
Volume
111
Issue
1
Copyright Statement
© The Author(s) 2025. Published by Oxford University Press on behalf of the Endocrine Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. See the journal About page for add itional terms.
License URL
Identifier
10.1210/clinem/dgaf342
Subjects
MASLD, NAFLD, multimorbidity, all-cause mortality, UK Biobank, long-term conditions, sexual dimorphism Abbreviations: BMI, body mass index
BP, blood pressure
CKD, chronic kidney disease
COPD, chronic obstructive pulmonary disease
FLI, fatty liver index
HbA1c, glycated hemoglobin
HDL, high-density lipoprotein
HSI, hepatic steatotic index
IHD, ischemic heart disease
LTC, long-term condition
MASLD, metabolic dysfunction-associated steatotic liver disease
NAFLD, nonalcoholic fatty liver disease
TG, triglyceride
Publication Status
Published
Article Number
dgaf342
Date Publish Online
2025-06-10