Time-Varying Impact of Steatosis and Alcohol on Mortality: A Marginal Structural Model of the Canadian Longitudinal Study on Aging

IF 6.2 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Liver International Pub Date : 2026-08-06 DOI:10.1111/liv.70833

Carmela Rapino, Giada Sebastiani, Jessica Burnside, Cindy Wen, Alnoor Ramji, Mark Swain, Keyur Patel, Sahar Saeed

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引用次数: 0

Abstract

Background and Aims

Subclassifications of steatotic liver disease (SLD) are intended to provide a clinically meaningful framework for management. However, steatosis, cardiometabolic comorbidities and alcohol consumption are known to change over time. We investigated the association of the dynamic classification of SLD subtypes and all-cause mortality.

Methods

We analysed data from the Canadian Longitudinal Study on Aging, a cohort of adults aged 45–85 years that is followed every 3 years or until death. Hepatic steatosis was identified using the NAFLD Ridge Score, and alcohol consumption was used to classify MASLD, MetALD and ALD. Marginal structural Cox proportional hazards models estimated associations between time-varying SLD subtypes and mortality. Models were adjusted for socio-demographic, lifestyle and cardiometabolic factors, and stratified by sex.

Results

Among 16 560 participants (52.1% female; median age 58 [IQR 51–66] years), 1041 deaths occurred within a median of 7.8 years. Within the first 3 years, 35.4%, 23.7% and 22.6% of participants with ALD, MetALD and MASLD, respectively, transitioned to different SLD subtypes. Mortality risk increased with increasing levels of alcohol among people with and without steatosis, and ALD demonstrated the highest mortality risk (aHR 6.11; 95% CI 1.76–21.19). Sex-stratified analyses suggested higher mortality among females, with the highest mortality rate in females with ALD compared to males (11.37 vs. 5.60 per 1000 person-years).

Conclusions

SLD phenotypes are dynamic, with substantial transitions between disease subtypes over time. Reliance on static classifications may therefore misclassify risk. Longitudinal, time-varying approaches better capture disease evolution and may improve prognostic assessment and risk stratification.

查看原文本刊更多论文

脂肪变性和酒精对死亡率的时变影响：加拿大老龄化纵向研究的边际结构模型。

背景和目的：脂肪变性肝病（SLD）的亚分类旨在为治疗提供一个有临床意义的框架。然而，脂肪变性、心脏代谢合并症和饮酒是随着时间而改变的。我们研究了SLD亚型的动态分类与全因死亡率的关系。方法：我们分析了来自加拿大老龄化纵向研究的数据，这是一组年龄在45-85岁之间的成年人，每3年随访一次，直到死亡。肝脂肪变性采用NAFLD Ridge评分进行鉴定，酒精摄入量用于对MASLD、MetALD和ALD进行分类。边际结构Cox比例风险模型估计时变SLD亚型与死亡率之间的关联。模型根据社会人口统计学、生活方式和心脏代谢因素进行调整，并按性别分层。结果：在16560名参与者中（52.1%为女性，中位年龄58岁[IQR 51-66]岁），1041例死亡发生在中位7.8年内。在前3年内，35.4%、23.7%和22.6%的ALD、MetALD和MASLD参与者分别转变为不同的SLD亚型。在有脂肪变性和没有脂肪变性的人群中，死亡风险随着酒精水平的增加而增加，ALD显示出最高的死亡风险（aHR 6.11; 95% CI 1.76-21.19）。性别分层分析显示，女性的死亡率更高，与男性相比，ALD患者的女性死亡率最高（11.37 vs. 5.60 / 1000人年）。结论：SLD表型是动态的，随着时间的推移，疾病亚型之间存在实质性的转变。因此，依赖静态分类可能会错误地对风险进行分类。纵向、时变方法能更好地捕捉疾病演变，并可能改善预后评估和风险分层。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Liver International 医学-胃肠肝病学

CiteScore

13.90

自引率

4.50%

发文量

348

审稿时长

2 months

期刊介绍： Liver International promotes all aspects of the science of hepatology from basic research to applied clinical studies. Providing an international forum for the publication of high-quality original research in hepatology, it is an essential resource for everyone working on normal and abnormal structure and function in the liver and its constituent cells, including clinicians and basic scientists involved in the multi-disciplinary field of hepatology. The journal welcomes articles from all fields of hepatology, which may be published as original articles, brief definitive reports, reviews, mini-reviews, images in hepatology and letters to the Editor.