Smoking and severity of hepatic fibrosis in nonalcoholic fatty liver disease☆

Articles in Press

Claudia O. Zein 12, Aynur Unalp 3, Ryan Colvin 3, Yao-Chang Liu 2, Arthur J. McCullough 12, for the Nonalcoholic Steatohepatitis Clinical Research Network

Received 22 March 2010; received in revised form 8 July 2010; accepted 16 July 2010. published online 18 November 2010.
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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.

Abbreviations: NAFLD, nonalcoholic fatty liver disease, NASH CRN, nonalcoholic steatohepatitis clinical research network, DM, type 2 diabetes mellitus, BMI, body mass index, SD, standard deviation, OR, odds ratio

Keywords: Smoking, Alcohol, Nonalcoholic fatty liver disease, Liver fibrosis, Predictors

1 Cleveland Clinic, Cleveland, OH, USA
2 Case Western Reserve University, Cleveland, OH, USA
3 Johns Hopkins University, Baltimore, MD, USA

Corresponding author at: Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, 9500 Euclid Ave., Cleveland, OH 44915, USA.

☆ This work was presented, in part, at the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), November 2007, Boston, MA.

PII: S0168-8278(10)00833-0
doi:10.1016/j.jhep.2010.07.040
© 2010 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.

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