Abstract
BACKGROUND & AIMS: Although many predictors of disease severity of nonalcoholic fatty liver disease (NAFLD) have been proposed, studies of the potential effects of specific environmental exposures on human NAFLD are lacking. Smoking increases insulin resistance. Given the pathophysiological role of insulin resistance in NAFLD, characterization of the influence of smoking in NAFLD is warranted. The aim of this paper was to study the potential association between cigarette smoking and advanced fibrosis in NAFLD. METHODS: All adults enrolled in the NASH CRN studies, between October 2004 and February 2008, who had liver biopsies, were included (n=1091). Advanced fibrosis was defined as stages 3-4. Analyses were performed. RESULTS: Significant bivariate associations were demonstrated between advanced fibrosis and age, gender, ethnicity, diabetes, and smoking history. History of smoking ≥ 10 pack-years was more common (p <0.0001) among patients with advanced fibrosis. Multivariate analysis demonstrated an association between smoking history of ≥ 10 pack-years and advanced fibrosis (OR=1.63). Among non-diabetics, history of ≥ 10 pack-years was associated with an OR of 2.48 for advanced fibrosis. High frequencies of advanced fibrosis were observed among diabetics (with or without ≥ 10 pack-years history) and non-diabetics with ≥ 10 pack-years history as compared to non-diabetics without significant smoking history. CONCLUSIONS: Smoking history was associated with advanced liver fibrosis in this large multicenter cohort of NAFLD patients. The results indicate that smoking may enhance the progression of NAFLD partly through its effect on insulin resistance. Our results are consistent with recent animal studies suggesting that cigarette smoke may aggravate fatty liver. To our knowledge, this is the first study to show that cigarette smoking is associated with increased fibrosis severity in human NALFD, suggesting it may accelerate disease progression. These results may support a formal recommendation of smoking cessation in patients with NAFLD.