Is cigarette smoking an independent risk factor or a cofactor for nonalcoholic fatty liver disease?

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Is Cigarette Smoking an Independent Risk Factor or a Cofactor for Nonalcoholic Fatty Liver Disease?

To the Editor:

We read with great interest the article by Azzalini et al. showing that cigarette smoking causes significant oxidative stress and worsens the severity of nonalcoholic fatty liver disease (NAFLD) in obese Zucker rats. Their results indeed provide important data for improving our understanding of the relationship between cigarette smoking and NAFLD. However, whether this association also holds true in humans remains unclear, nor is it clear whether cigarette smoking independently increases the risk for NAFLD.

Recently, we conducted a cross-sectional study to analyze the association of cigarette smoking with NAFLD. We included 8442 employees (5369 males; mean age = 46.6 years) of Zhenhai Refining and Chemical Company, Ltd. (Ningbo, China), who were attending their annual health examination between January 1, 2008 and December 31, 2008. Most of the subjects were also included in our previous studies.1, 2 Here we observed that the prevalence rate of NAFLD was significantly higher among cigarette smokers versus nonsmokers (28.27% versus 19.18%, P < 0.001). We further classified all the subjects into four groups according to their smoking severity. In comparison with nonsmokers, the prevalence ratios for mild (1-10 cigarettes daily), moderate (11-20 cigarettes daily), and severe smokers (>20 cigarettes daily) were 1.33, 1.51, and 1.71, respectively (P for trend < 0.001). These results suggest that cigarette smokers are more likely to develop NAFLD than nonsmokers, and the likelihood increases with increasing severity of cigarette smoking.

Metabolic syndrome is a well-established risk factor for NAFLD.3, 4 An analysis of the relationship between cigarette smoking and metabolic syndrome may indirectly reflect the relationship between cigarette smoking and NAFLD. Therefore, the impact of cigarette smoking on the prevalence ratio of metabolic syndrome and its components was studied. We observed that the prevalence ratios of metabolic syndrome, central obesity, hypertriglyceridemia, elevated blood pressure, and elevated fasting plasma glucose all tended to increase with increases in cigarette smoking severity (Fig. 1). These results not only confirm that cigarette smoking is an important factor for metabolic syndrome5, 6 but also indirectly indicate that cigarette smoking may be a significant factor for NAFLD, which is closely related to metabolic syndrome.

Figure 1.

Prevalence rate of metabolic syndrome with different severities of cigarette smoking. The prevalence rates of metabolic syndrome and its components, including central obesity, hypertriglyceridemia, elevated blood pressure (BP) and elevated fasting plasma glucose (FPG), all showed increasing trends with increasing severity of cigarette smoking.

Finally, we performed logistic regression analysis to evaluate whether cigarette smoking is an independent risk factor for NAFLD. In a univariate model, cigarette smoking was observed to be a significant risk factor for NAFLD with an odds ratio of 1.31 (95% confidence interval = 1.23-1.40). However, adjustments for age, gender, and body mass index significantly attenuated the odds ratio to 1.09 (1.00-1.18). In a multivariate model, cigarette smoking was not significantly statistically associated with the risk for NAFLD. This analysis indicated that the relationship between cigarette smoking and NAFLD may be somehow influenced by other variables.

Together, our results provide evidence that the association between cigarette smoking and NAFLD observed in rats may also hold true in humans. Our results also indicate that cigarette smoking may act as a cofactor but not as an independent factor for NAFLD.

Cheng-Fu Xu M.D.*, Chao-Hui Yu M.D., Ph.D.*, Lei Xu M.D.* †, Min Miao M.D.‡, You-Ming Li M.D.*, * Department of Gastroenterology, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China, † Department of Gastroenterology, Ningbo No. 1 Hospital, Ningbo, China, ‡ Department of Internal Medicine, Hospital of Zhenhai Refining and Chemical Company, Ningbo, China.

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