Unequal mortality risks in steatotic liver disease beyond liver: influence of disease subtypes and fibrosis
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Published version (article in press)
Author(s)
Feng, Qi
Izzi-Engbeaya, Chioma
Woodward, Mark
Manousou, Pinelopi
Type
Journal Article
Abstract
Background and aims
To examine mortality risks associated with steatotic liver disease (SLD), focusing on how disease subtypes (MASLD, MetALD, ALD), and fibrosis severity shape cause-specific mortality across a broad spectrum of diseases.
Methods
We analysed 486156 UK Biobank participants. Causes of death were summarised by SLD subtypes. Multivariable Cox models estimated associations between SLD, its subtypes, and fibrosis severity (FIB4 score), with cause-specific mortality outcomes across ICD10 disease categories.
Results
Among 178336 participants with SLD, 20766 died over a median follow up of 13.8 years. The leading causes of deaths were neoplasm (46.4%), circulatory disease (24.2%), respiratory disease (7.0%), and digestive disease (4.8%). Compared to participants without SLD (n = 307820), those with SLD had significantly higher mortality from neoplasm (HR 1.24 (1.20, 1.28)), circulatory (1.57 (1.50, 1.64)), and digestive diseases (1.85 (1.67, 2.05)), as well as from metabolic, and genitourinary diseases, across all FIB4 score levels. Elevated risks were also observed for mortality from diabetes (3.40 (2.59, 4.46)), Covid-19 (1.97 (1.76, 2.21)), myocardial infarction (1.69 (1.53, 1.86)), stroke (1.24 (1.04, 1.48)), and several cancers, such as breast (1.50 (1.35, 1.68)), colorectal (1.22 (1.11, 1.34)), and prostate cancer (1.22 (1.09, 1.37)). Importantly, SLD subtypes exhibited distinct and unequal patterns of cause-specific mortality, with further stratification by fibrosis severity revealing graded risk differentials.
Conclusion
SLD is associated with unequal mortality risks across a wide range of disease categories, driven by substantial heterogeneity across subtypes, fibrosis severity and outcomes. Extrahepatic cancers and circulatory diseases contribute most to overall mortality, but the magnitude of risk varies markedly. These findings highlight the need for risk-stratified, multidisciplinary management strategies that account for both subtypes and fibrosis stage, targeting liver progression, cardiometabolic burden, and cancer prevention.
To examine mortality risks associated with steatotic liver disease (SLD), focusing on how disease subtypes (MASLD, MetALD, ALD), and fibrosis severity shape cause-specific mortality across a broad spectrum of diseases.
Methods
We analysed 486156 UK Biobank participants. Causes of death were summarised by SLD subtypes. Multivariable Cox models estimated associations between SLD, its subtypes, and fibrosis severity (FIB4 score), with cause-specific mortality outcomes across ICD10 disease categories.
Results
Among 178336 participants with SLD, 20766 died over a median follow up of 13.8 years. The leading causes of deaths were neoplasm (46.4%), circulatory disease (24.2%), respiratory disease (7.0%), and digestive disease (4.8%). Compared to participants without SLD (n = 307820), those with SLD had significantly higher mortality from neoplasm (HR 1.24 (1.20, 1.28)), circulatory (1.57 (1.50, 1.64)), and digestive diseases (1.85 (1.67, 2.05)), as well as from metabolic, and genitourinary diseases, across all FIB4 score levels. Elevated risks were also observed for mortality from diabetes (3.40 (2.59, 4.46)), Covid-19 (1.97 (1.76, 2.21)), myocardial infarction (1.69 (1.53, 1.86)), stroke (1.24 (1.04, 1.48)), and several cancers, such as breast (1.50 (1.35, 1.68)), colorectal (1.22 (1.11, 1.34)), and prostate cancer (1.22 (1.09, 1.37)). Importantly, SLD subtypes exhibited distinct and unequal patterns of cause-specific mortality, with further stratification by fibrosis severity revealing graded risk differentials.
Conclusion
SLD is associated with unequal mortality risks across a wide range of disease categories, driven by substantial heterogeneity across subtypes, fibrosis severity and outcomes. Extrahepatic cancers and circulatory diseases contribute most to overall mortality, but the magnitude of risk varies markedly. These findings highlight the need for risk-stratified, multidisciplinary management strategies that account for both subtypes and fibrosis stage, targeting liver progression, cardiometabolic burden, and cancer prevention.
Date Issued
2026-08-21
Date Acceptance
2026-08-16
Citation
Diabetology and Metabolic Syndrome, 2026
ISSN
1758-5996
Publisher
BMC
Journal / Book Title
Diabetology and Metabolic Syndrome
Copyright Statement
© The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
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Publication Status
Published online
Date Publish Online
2026-08-21