Cigarette Smoking Increased Risk of Overall Mortality in Patients With Non-alcoholic Fatty Liver Disease: A Nationwide Population-Based Cohort Study

Background: The evidence suggests a detrimental effect of cigarette smoking on the progression of chronic liver disease. However, the impact of cigarette smoking on mortality among patients with nonalcoholic fatty liver disease (NAFLD) remain unclear. Methods: We used the National Health Examination Survey data collected during 2008-2009 to link the National Death Index to follow-up respondent survival. Diagnosis of NAFLD was based on a lipid accumulation product in participants without significant alcohol use or other liver diseases. Results: During 64,116 person-years of follow-up, 928 of 7,529 participants with NAFLD died, and the cumulative all-cause mortality was 14.5 per 1,000 person-years. In a Cox regression model adjusted for age, body mass index, alcohol intake, exercise, comorbidities, lipid profiles, and handgrip strength, current smoking increased the risk of mortality by 109% (adjusted hazard ratio (aHR): 2.09, 95% confidence interval [CI]: 1.18-3.71) compared with never smoker status in women, but showed only a trend toward harm among men (aHR: 1.41, 95% CI: 0.96-2.08). After controlling for potential confounders, smoking ≥10 pack-years continued to show a significant harmful effect on all-cause mortality among women (aHR: 5.40, 95% CI: 2.19-13.4), but not in men. Among women who drink alcohol ≥10 grams per day, current smoking (aHR: 13.8, 95% CI: 1.66-145) and smoking ≥10 pack-years (aHR: 310, 95% CI: 78-1,296) also significantly increased risk of death. Conclusion: This nationwide population-based study highlight a detrimental effect of cigarette smoking on mortality, with a similar but more definite association in women than in men with NAFLD.