Smoking and the Risk of Non-Alcoholic Fatty Liver Disease: A Cohort Study

OBJECTIVES: The role of smoking in the development of non-alcoholic fatty liver disease (NAFLD) remains controversial. We assessed the risk of incident NAFLD according to smoking status and urinary cotinine levels. METHODS: We performed a cohort study of 199,468 Korean adults without NAFLD at baseline who were followed annually or biennially for a median of 4.1 years. The presence of fatty liver was determined using ultrasound. NAFLD severity was assessed using NAFLD fibrosis score (NFS), a non-invasive fibrosis marker. RESULTS: During 1,070,991 person-years of follow-up, 45,409 participants developed NAFLD. Self-reported current smoking, pack-years, and urinary cotinine level were significantly associated with increased risk for NAFLD. For men, the multivariable-adjusted hazard ratios (aHR) (95% confidence intervals (CI)) for incident NAFLD comparing 10-19.9, and ≥20 pack-years to 0 pack-years were 1.25 (1.21- 1.29), and 1.36 (1.30-1.42), respectively; for women, aHR (95% CI) for NAFLD comparing 5-9.9, and ≥10 pack-years to 0 pack-years were 1.25 (1.04-1.50), and 1.46 (1.17-1.81), respectively. Smoking pack-years were also associated with increased risk for NAFLD plus intermediate or high fibrosis score. For men, the aHR (95% CI) for NAFLD plus intermediate or high NFS comparing ≥20 pack-years to 0 pack-years was 1.29 (1.18-1.42); for women, the aHR (95% CI) comparing ≥10 pack-years to 0 pack-years was 1.75 (1.12-2.73). CONCLUSIONS: In a large cohort of young and middle-aged men and women, current smoking, pack-years, and urinary cotinine levels were positively associated with the risk of incident NAFLD, suggesting that smoking contributes to the development of NAFLD.