Abstract
BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is an increasingly prevalent liver disorder. OBJECTIVES: This study investigated the effect of smoking status on various clinical outcomes in MASLD and metabolic dysfunction and alcohol-associated liver disease (MetALD). DESIGN: This study is a retrospective cohort analysis utilizing data from the UK Biobank (Application ID: 117214). Participants were categorized as current, previous, or never smokers, and outcomes were analyzed using inverse probability of treatment weighting to adjust for confounders. METHODS: The primary outcomes were all-cause mortality and liver-related mortality. Secondary outcomes included incidence of liver cirrhosis, hepatic decompensation, cardio-cerebrovascular diseases (CVD), and hepatocellular carcinoma (HCC). Multivariate Cox proportional hazards models were employed to evaluate associations. RESULTS: Previous and never smokers had significantly lower hazard ratios (HRs) for mortality compared to current smokers in all cohorts (HR: 0.33, 95% confidence interval (CI): 0.31-0.35, p < 0.001 for never smokers in No SLD cohort, HR: 0.43, 95% CI: 0.41-0.44, p < 0.001 for never smokers in MASLD cohort, and HR: 0.41, 95% CI: 0.38-0.45, p < 0.001 for never smokers in MetALD cohort). Previous and never smokers showed significantly lower incidences of liver cirrhosis compared to current smokers across all cohorts, except for MetALD. Previous and never smokers showed lower incidences of CVD compared to current smokers. In the MASLD cohort, never smokers had the lowest incidence of hepatic decompensation and HCC. In the MetALD cohort, no significant differences were observed in the risk of hepatic decompensation and HCC between different smoking statuses. CONCLUSION: Smoking is related to worse survival outcomes and higher incidences of liver cirrhosis and CVD in MASLD and MetALD cohorts. Therefore, smoking cessation and prevention are crucial strategies for reducing the burden of liver disease and improving patient prognosis.