脂肪性肝病中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及多种肝脏和肝外结局的影响

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.

作者信息

Cuthbertson Daniel J, Kennedy Oliver J, Bilson Josh, Hydes Theresa J, Targher Giovanni, Glyn-Owen Kate, Buchanan Ryan, Roderick Paul, Byrne Christopher D

机构信息

Department of Cardiovascular and Metabolic Medicine, University of Liverpool, Liverpool, Merseyside, UK; Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside, UK; Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside, UK.

Primary Care and Population Sciences, Faculty of Medicine, University of Southampton, Southampton, UK; Division of Cancer Sciences, The University of Manchester, Manchester M13 9PL, UK.

出版信息

Metabolism. 2025 Sep;170:156306. doi: 10.1016/j.metabol.2025.156306. Epub 2025 May 23.

DOI:10.1016/j.metabol.2025.156306

PMID:40414560

Abstract

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.

摘要

背景

在代谢功能障碍相关脂肪性肝病（MASLD）以及伴有酒精摄入的MASLD（MetALD）中，我们研究了代谢功能障碍的严重程度对主要不良肝脏结局（MALO）、主要心血管事件（MACE）、肥胖相关癌症以及全因死亡率（ACM）的影响。

方法

在502381名英国生物银行参与者中，使用肝脂肪变性指数（HSI）（>36对<30）来识别脂肪性肝病（SLD）。采用MASLD/MetALD标准确定代谢综合征（MetS）特征和MetS（≥3个特征）。使用Cox回归估计MASLD或MetALD加1至5个MetS特征与MALO、MACE、肥胖相关癌症的发生以及5年/10年发病率的调整风险比和95%置信区间[aHR(95%CIs)]，并与对照组（无SLD/MetS特征）进行比较。

结果

中位随访时间为148至149个月。分别将具有1个和5个MetS特征的MASLD与对照组进行比较；对于MALO而言，[aHRs(95%CIs)]分别为2.27（1.03 - 5.00）和9.19（4.98 - 16.95）；对于MetALD，aHRs分别为1.65（0.53 - 5.11）和8.54（3.65 - 19.95）。对于MACE，在MASLD中，aHRs分别为1.51（1.19 - 1.92）和4.81（4.06 - 5.69）；在MetALD中，aHRs分别为1.46（1.00 - 2.13）和4.64（3.51 - 6.14）。对于肥胖相关癌症，在MASLD中，aHRs分别为1.04（0.87 - 1.23）和1.46（1.29 - 1.66）；在MetALD中，aHRs分别为1.01（0.79 - 1.29）和1.51（1.24 - 1.83）。5年和10年发病率也随着MetS特征数量的增加而逐渐升高。在MASLD和MetALD中，将SLD、MetS和高肝纤维化风险（由FIB-4≥2.67定义）相结合与MALO密切相关（aHRs分别为27.48，(17.72 - 42.61)；43.36，20.53 - 91.58）。