Sex, Metabolic Profiles, and Alcohol: Evaluating the Prognostic Significance of Steatotic Liver Disease Classifications in the Canadian Longitudinal Study on Aging (CLSA)
Year: 2026
Type: dissertation
Abstract: Background: The subclassifications of Steatotic Liver Disease (SLD) were intended to provide a clinically meaningful framework for assessing prognosis and guiding intervention that encompasses a spectrum of mixed aetiologies combining metabolic dysfunction and increasing levels of alcohol consumption. However, little consideration is given to the disease's dynamic nature over time. We aimed to evaluate the association between increasing levels of alcohol consumption and all-cause mortality in those with and without steatosis. Methodology: We analyzed data from the Canadian Longitudinal Study on Aging, a prospective cohort study following adults aged 45-85 years between baseline (2012-2015), 3 years later for follow-up 1 (FUP1), and until 2021(follow-up 2). Hepatic steatosis was identified using the NAFLD Ridge Score, with cardiometabolic factors determined from laboratory and medication data. Alcohol consumption was quantified using self-reported weekly intake and used to define SLD subclasses (MASLD, MetALD and ALD). Time-varying, and Marginal Structural Model Cox proportional hazards models were used to estimate the association between increasing levels of alcohol consumption and mortality among those with and without steatosis, overall and sex-stratified, adjusting for age, income, physical activity, diet, smoking, binge drinking, sex, and the cumulative number of cardiometabolic factors. Results: Between 2012 and 2021, 16,560 participants (52.1% female, median age 58 (IQR: 51-66)) were included. At baseline, MASLD was the most prevalent subtype at baseline (n = 8430 | 33.9%). Between baseline to FUP1, 35.4% of people with ALD, 23.7% MetALD, and 22.6% MASLD transitioned to different SLD subtypes. Over a median follow-up of 7.8 years, 1041 deaths occurred. Overall, steatosis increased the risk of death and after accounting for time-varying exposures and confounders, ALD had the highest risk of all-cause mortality (adjusted hazard ratio (aHR) 6.11 | 95% CI: 1.76-21.19). Conclusion: SLD is dynamic, with evolving mortality risks that cannot be captured by baseline classifications alone. Incorporating time-varying covariates yields a more accurate understanding of prognosis.
Author: Rapino, Carmela
Institution: Queen's University
Language: English
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1310812557, G6227940160, G8059889987
OpenAlex ID: W7213382104