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 non-alcoholic 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.