Abstract
BACKGROUND AND AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent, and smoking is associated with greater disease severity. We investigated whether documented smoking cessation attempts among adults with MASLD were associated with liver-related outcomes, cardiovascular outcomes, and all-cause mortality. METHODS: We performed a retrospective cohort study using the TriNetX Research Network. Adults (≥ 18 years) with MASLD and documented smoking history were included. A smoking cessation attempt was defined by cessation counseling and/or cessation pharmacotherapy; comparators had no documented cessation attempt. Patients with depressive disorders and competing liver etiologies were excluded. Cohorts were matched 1:1 using propensity scores, and outcomes were analyzed using Cox proportional hazards models. Sensitivity analyses were performed at fixed follow-up horizons of 6 months, 1 year, and 2 years. RESULTS: Among 418,784 eligible patients, 85,639 had a documented cessation attempt and 333,145 did not; after matching, 83,315 patients remained in each cohort. In the matched cohort, cessation attempt was associated with lower hazards of cirrhosis progression (1.7% vs. 2.1%; HR 0.87, 95% CI 0.81-0.93), hepatocellular carcinoma (0.2% vs. 0.3%; HR 0.58, 95% CI 0.48-0.70), portal hypertension (0.8% vs. 1.1%; HR 0.77, 95% CI 0.70-0.86), and MASH progression (2.2% vs. 2.9%; HR 0.76, 95% CI 0.71-0.81). The cessation attempt was also associated with higher hazards of MACE (13.6% vs. 11.4%; HR 1.24, 95% CI 1.20-1.28), peripheral artery disease (4.1% vs. 3.2%; HR 1.33, 95% CI 1.26-1.40), and all-cause mortality (8.5% vs. 7.3%; HR 1.23, 95% CI 1.18-1.27). Fixed-horizon analyses showed similar patterns over time. CONCLUSIONS: In adults with MASLD and smoking history, documented smoking cessation attempts were associated with lower hazards of several liver outcomes but higher cardiovascular event rates and mortality, findings likely influenced by residual confounding and clinical risk clustering in patients receiving cessation interventions.