S2487 Comparative Analysis of Mortality and Clinical Outcomes in MASLD Patients: Active Smokers vs Former Smokers Using the TriNetX Database—A Propensity-Matched Cohort Study

Introduction: Metabolic dysfunction associated liver disease (MASLD) is a leading cause of chronic liver disease worldwide, with smoking status potentially influencing disease progression and clinical outcomes. This study aimed to compare mortality and cardiovascular outcomes between MASLD patients who are active smokers versus former smokers. Methods: We performed a retrospective cohort study using the TriNetX Research Network, a global federated health research platform providing access to electronic medical records across 145 healthcare organizations. Patients with MASLD (International Classification of Diseases, Tenth Revision code K76.0) were stratified by smoking status: active smokers versus former smokers. After propensity score matching, cohorts of 5,650 patients each were analyzed. Primary outcome was all-cause mortality. Secondary outcomes included heart failure, chronic kidney disease, atrial fibrillation and flutter, cerebrovascular disease, coronary artery disease, diabetes mellitus, liver cirrhosis, and hypertension. Outcomes were analyzed using risk analysis and Kaplan-Meier survival analysis with hazard ratios (HR) and 95% confidence intervals (CI) over 5 years. Results: Active smokers with MASLD demonstrated similar all-cause mortality compared to former smokers (10.0% vs 9.6%; HR 1.073, 95% CI 0.953-1.207; P = 0.154). However, active smokers had significantly higher rates of heart failure (7.6% vs 6.3%; HR 1.220, 95% CI 1.045-1.424; P = 0.012), cerebrovascular disease (9.6% vs 7.7%; HR 1.284, 95% CI 1.116-1.478; P < 0.001), coronary artery disease (10.5% vs 9.1%; HR 1.188, 95% CI 1.034-1.365; P = 0.015), diabetes mellitus (10.3% vs 8.9%; HR 1.188, 95% CI 1.023-1.379; P = 0.023), liver cirrhosis (4.8% vs 3.6%; HR 1.375, 95% CI 1.135-1.666; P = 0.001), and hypertension (22.5% vs 18.1%; HR 1.292, 95% CI 1.127- 1.481; P < 0.001). No significant differences were observed in chronic kidney disease, atrial fibrillation and flutter, or pulmonary embolism. Conclusion: Among MASLD patients, active smoking is associated with significantly higher rates of cardiovascular complications, liver cirrhosis, and diabetes mellitus compared to former smoking, despite similar overall mortality. These findings underscore the importance of smoking cessation interventions in MASLD patients to reduce disease-related complications and support the need for comprehensive cardiovascular risk management in this population.