Unveiling the burden of steatotic liver disease: mortality risks by subtype and fibrosis stage in a nationwide cohort
Author(s)
Type
Journal Article
Abstract
Background and Aims
We investigated the associations between SLD, fibrosis stage, and all-cause and cause-specific mortality, with a focus on SLD subtypes.
Methods
We analysed 486 156 UK Biobank participants. SLD cases were identified using fatty liver index ≥ 60. Causes of death were confirmed via death registries. Multivariable Cox models estimated associations between SLD, SLD subtypes, FIB4 score and mortality outcomes, including all-cause mortality, mortality from liver-related diseases, cardiovascular disease (CVD) and extrahepatic cancers.
Results
SLD was identified in 178 336 participants (36.7%): 73.5% with MASLD, 19.0% with MetALD and 6.4% with ALD. Over a median follow-up of 13.8 years, 20 766 (11.6%) deaths occurred among people with SLD and 21 754 among those without (307 820; 7.1%), suggesting a higher mortality rate in SLD than in non-SLD (8.78 vs. 5.25/1000 person-years). All SLD subtypes were associated with higher all-cause mortality: MASLD (HR (95% CI): 1.32 (1.29–1.35)), MetALD (1.16 (1.12–1.20)) and ALD (1.36 (1.29–1.44)). Excess mortality was primarily driven by extrahepatic cancer (42.5%) and cardiovascular disease (24.2%), while liver-related deaths were concentrated among those with ALD and fibrosis. A strong dose–response relationship was observed between FIB4 stratification and mortality, particularly for liver-related deaths. These associations were independent of socioeconomic status, lifestyle and cardiometabolic risk factors.
Conclusion
SLD is independently associated with increased all-cause and cause-specific mortality, with substantial variation across subtypes and fibrosis severity. Extrahepatic cancer and cardiovascular disease are the leading contributors to excess mortality. These findings underscore the need for integrated care strategies targeting metabolic risk, fibrosis progression and cancer prevention in the SLD population.
We investigated the associations between SLD, fibrosis stage, and all-cause and cause-specific mortality, with a focus on SLD subtypes.
Methods
We analysed 486 156 UK Biobank participants. SLD cases were identified using fatty liver index ≥ 60. Causes of death were confirmed via death registries. Multivariable Cox models estimated associations between SLD, SLD subtypes, FIB4 score and mortality outcomes, including all-cause mortality, mortality from liver-related diseases, cardiovascular disease (CVD) and extrahepatic cancers.
Results
SLD was identified in 178 336 participants (36.7%): 73.5% with MASLD, 19.0% with MetALD and 6.4% with ALD. Over a median follow-up of 13.8 years, 20 766 (11.6%) deaths occurred among people with SLD and 21 754 among those without (307 820; 7.1%), suggesting a higher mortality rate in SLD than in non-SLD (8.78 vs. 5.25/1000 person-years). All SLD subtypes were associated with higher all-cause mortality: MASLD (HR (95% CI): 1.32 (1.29–1.35)), MetALD (1.16 (1.12–1.20)) and ALD (1.36 (1.29–1.44)). Excess mortality was primarily driven by extrahepatic cancer (42.5%) and cardiovascular disease (24.2%), while liver-related deaths were concentrated among those with ALD and fibrosis. A strong dose–response relationship was observed between FIB4 stratification and mortality, particularly for liver-related deaths. These associations were independent of socioeconomic status, lifestyle and cardiometabolic risk factors.
Conclusion
SLD is independently associated with increased all-cause and cause-specific mortality, with substantial variation across subtypes and fibrosis severity. Extrahepatic cancer and cardiovascular disease are the leading contributors to excess mortality. These findings underscore the need for integrated care strategies targeting metabolic risk, fibrosis progression and cancer prevention in the SLD population.
Date Issued
2026-02-01
Date Acceptance
2025-12-10
Citation
Liver International, 2026, 46 (2)
ISSN
1478-3223
Publisher
Wiley
Journal / Book Title
Liver International
Volume
46
Issue
2
Copyright Statement
© 2025 The Author(s). Liver International published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/41460581
Subjects
ALD
MASLD
MetALD
cancers
cardiovascular diseases
fibrosis
mortality
steatotic liver disease
Humans
Male
Female
Middle Aged
Liver Cirrhosis
Aged
United Kingdom
Cause of Death
Proportional Hazards Models
Cardiovascular Diseases
Fatty Liver
Risk Factors
Non-alcoholic Fatty Liver Disease
Severity of Illness Index
Adult
Cohort Studies
Publication Status
Published
Coverage Spatial
United States
Article Number
e70485
Date Publish Online
2025-12-29