Daniel J. Cuthbertson , Oliver J. Kennedy , Josh Bilson , Theresa J. Hydes , Giovanni Targher , Kate Glyn-Owen , Ryan Buchanan , Paul Roderick , Christopher D. Byrne
{"title":"脂肪变性肝病代谢功能障碍严重程度及其与肝纤维化的相互作用对全因死亡率和多肝及肝外预后的影响","authors":"Daniel J. Cuthbertson , Oliver J. Kennedy , Josh Bilson , Theresa J. Hydes , Giovanni Targher , Kate Glyn-Owen , Ryan Buchanan , Paul Roderick , Christopher D. Byrne","doi":"10.1016/j.metabol.2025.156306","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>In metabolic dysfunction-associated steatotic liver disease (MASLD) and in MASLD with alcohol consumption (MetALD), we investigated the effect of severity of metabolic dysfunction on incident major adverse liver outcomes (MALO), major cardiovascular events (MACE), obesity-related cancers, and all-cause mortality (ACM).</div></div><div><h3>Methods</h3><div>SLD was identified among 502,381 UK Biobank participants using the Hepatic Steatosis Index (HSI) (>36 <em>vs.</em><30). Metabolic syndrome (MetS) traits and MetS (≥3 traits) using MASLD/MetALD criteria. Cox regression was used to estimate adjusted hazard ratios and 95%CIs [aHR(95%CIs)] of MASLD or MetALD <em>plus</em> 1 to 5 MetS traits with incident MALO, MACE, obesity-related cancers and 5-year/10-year incidence rates <em>versus</em> reference (no SLD/MetS traits).</div></div><div><h3>Results</h3><div>Median follow-up was 148 to 149 months. Comparing MASLD with one <em>versus</em> five MetS traits, respectively, to the reference; for MALO, [aHRs (95%CIs)] were 2.27 (1.03–5.00) and 9.19 (4.98–16.95); for MetALD, aHRs were 1.65 (0.53–5.11) and 8.54 (3.65–19.95) respectively. For MACE, with MASLD; aHRs were 1.51 (1.19–1.92) and 4.81 (4.06–5.69) respectively; with MetALD, aHRs were 1.46 (1.00–2.13) and 4.64 (3.51–6.14) respectively. For obesity-related cancers; with MASLD, aHRs were 1.04 (0.87–1.23) and 1.46 (1.29–1.66) respectively; with MetALD, aHRs were 1.01 (0.79–1.29) and 1.51 (1.24–1.83) respectively. 5-year and 10-year incidence rates also increased progressively with increasing MetS traits. Combining SLD, MetS and high liver fibrosis risk (defined by FIB-4 ≥ 2.67) was strongly associated with MALO in both MASLD and MetALD (aHRs 27.48, (17.72–42.61); 43.36, 20.53–91.58 respectively).</div></div><div><h3>Conclusion</h3><div>In MASLD or MetALD, the numbers of MetS traits markedly influence risk and incidence of liver-related outcomes, MACE, obesity-related cancers and ACM.</div></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"170 ","pages":"Article 156306"},"PeriodicalIF":10.8000,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Impact of metabolic dysfunction severity in steatotic liver disease and its interaction with liver fibrosis on all-cause mortality and multiple hepatic and extra-hepatic outcomes\",\"authors\":\"Daniel J. Cuthbertson , Oliver J. Kennedy , Josh Bilson , Theresa J. Hydes , Giovanni Targher , Kate Glyn-Owen , Ryan Buchanan , Paul Roderick , Christopher D. Byrne\",\"doi\":\"10.1016/j.metabol.2025.156306\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>In metabolic dysfunction-associated steatotic liver disease (MASLD) and in MASLD with alcohol consumption (MetALD), we investigated the effect of severity of metabolic dysfunction on incident major adverse liver outcomes (MALO), major cardiovascular events (MACE), obesity-related cancers, and all-cause mortality (ACM).</div></div><div><h3>Methods</h3><div>SLD was identified among 502,381 UK Biobank participants using the Hepatic Steatosis Index (HSI) (>36 <em>vs.</em><30). Metabolic syndrome (MetS) traits and MetS (≥3 traits) using MASLD/MetALD criteria. Cox regression was used to estimate adjusted hazard ratios and 95%CIs [aHR(95%CIs)] of MASLD or MetALD <em>plus</em> 1 to 5 MetS traits with incident MALO, MACE, obesity-related cancers and 5-year/10-year incidence rates <em>versus</em> reference (no SLD/MetS traits).</div></div><div><h3>Results</h3><div>Median follow-up was 148 to 149 months. Comparing MASLD with one <em>versus</em> five MetS traits, respectively, to the reference; for MALO, [aHRs (95%CIs)] were 2.27 (1.03–5.00) and 9.19 (4.98–16.95); for MetALD, aHRs were 1.65 (0.53–5.11) and 8.54 (3.65–19.95) respectively. For MACE, with MASLD; aHRs were 1.51 (1.19–1.92) and 4.81 (4.06–5.69) respectively; with MetALD, aHRs were 1.46 (1.00–2.13) and 4.64 (3.51–6.14) respectively. For obesity-related cancers; with MASLD, aHRs were 1.04 (0.87–1.23) and 1.46 (1.29–1.66) respectively; with MetALD, aHRs were 1.01 (0.79–1.29) and 1.51 (1.24–1.83) respectively. 5-year and 10-year incidence rates also increased progressively with increasing MetS traits. Combining SLD, MetS and high liver fibrosis risk (defined by FIB-4 ≥ 2.67) was strongly associated with MALO in both MASLD and MetALD (aHRs 27.48, (17.72–42.61); 43.36, 20.53–91.58 respectively).</div></div><div><h3>Conclusion</h3><div>In MASLD or MetALD, the numbers of MetS traits markedly influence risk and incidence of liver-related outcomes, MACE, obesity-related cancers and ACM.</div></div>\",\"PeriodicalId\":18694,\"journal\":{\"name\":\"Metabolism: clinical and experimental\",\"volume\":\"170 \",\"pages\":\"Article 156306\"},\"PeriodicalIF\":10.8000,\"publicationDate\":\"2025-05-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Metabolism: clinical and experimental\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0026049525001751\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Metabolism: clinical and experimental","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0026049525001751","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
Impact of metabolic dysfunction severity in steatotic liver disease and its interaction with liver fibrosis on all-cause mortality and multiple hepatic and extra-hepatic outcomes
Background
In metabolic dysfunction-associated steatotic liver disease (MASLD) and in MASLD with alcohol consumption (MetALD), we investigated the effect of severity of metabolic dysfunction on incident major adverse liver outcomes (MALO), major cardiovascular events (MACE), obesity-related cancers, and all-cause mortality (ACM).
Methods
SLD was identified among 502,381 UK Biobank participants using the Hepatic Steatosis Index (HSI) (>36 vs.<30). Metabolic syndrome (MetS) traits and MetS (≥3 traits) using MASLD/MetALD criteria. Cox regression was used to estimate adjusted hazard ratios and 95%CIs [aHR(95%CIs)] of MASLD or MetALD plus 1 to 5 MetS traits with incident MALO, MACE, obesity-related cancers and 5-year/10-year incidence rates versus reference (no SLD/MetS traits).
Results
Median follow-up was 148 to 149 months. Comparing MASLD with one versus five MetS traits, respectively, to the reference; for MALO, [aHRs (95%CIs)] were 2.27 (1.03–5.00) and 9.19 (4.98–16.95); for MetALD, aHRs were 1.65 (0.53–5.11) and 8.54 (3.65–19.95) respectively. For MACE, with MASLD; aHRs were 1.51 (1.19–1.92) and 4.81 (4.06–5.69) respectively; with MetALD, aHRs were 1.46 (1.00–2.13) and 4.64 (3.51–6.14) respectively. For obesity-related cancers; with MASLD, aHRs were 1.04 (0.87–1.23) and 1.46 (1.29–1.66) respectively; with MetALD, aHRs were 1.01 (0.79–1.29) and 1.51 (1.24–1.83) respectively. 5-year and 10-year incidence rates also increased progressively with increasing MetS traits. Combining SLD, MetS and high liver fibrosis risk (defined by FIB-4 ≥ 2.67) was strongly associated with MALO in both MASLD and MetALD (aHRs 27.48, (17.72–42.61); 43.36, 20.53–91.58 respectively).
Conclusion
In MASLD or MetALD, the numbers of MetS traits markedly influence risk and incidence of liver-related outcomes, MACE, obesity-related cancers and ACM.
期刊介绍:
Metabolism upholds research excellence by disseminating high-quality original research, reviews, editorials, and commentaries covering all facets of human metabolism.
Consideration for publication in Metabolism extends to studies in humans, animal, and cellular models, with a particular emphasis on work demonstrating strong translational potential.
The journal addresses a range of topics, including:
- Energy Expenditure and Obesity
- Metabolic Syndrome, Prediabetes, and Diabetes
- Nutrition, Exercise, and the Environment
- Genetics and Genomics, Proteomics, and Metabolomics
- Carbohydrate, Lipid, and Protein Metabolism
- Endocrinology and Hypertension
- Mineral and Bone Metabolism
- Cardiovascular Diseases and Malignancies
- Inflammation in metabolism and immunometabolism