Reply to: “Smoking and NASH: A hidden message from the GREACE trial”
Authors: Claudia O. Zein, Arthur J. McCullough, Aynur Unalp
Journal: Journal of Hepatology (2011)

Smoking and severity of hepatic fibrosis in nonalcoholic fatty liver diseaseJournal of HepatologyVol. 54Issue 4PreviewAlthough 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. Full-Text PDF Smoking and NASH: A hidden message from the GREACE trialJournal of HepatologyVol. 56Issue 1PreviewThe article by Zein et al. in the April issue of this Journal adds to a growing body of evidence that tobacco use may be linked to progression of non-alcoholic fatty liver disease (NAFLD) [1]. However, while there was an association between the degree of fibrosis and tobacco use among the 1091 patients studied, the authors mention that they could not, surprisingly, find an association between NASH and current tobacco use. Another recent trial may provide some data regarding this. Full-Text PDF Open AccessSmoking and non-alcoholic steatohepatitis (NASH): The GREek Atorvastatin and Coronary heart disease Evaluation (GREACE) trialJournal of HepatologyVol. 57Issue 2PreviewAs the authors of the GREek Atorvastatin and Coronary heart disease Evaluation (GREACE) trial [1], we appreciate the comments made by Babu et al. [2] and Zein et al. [3] regarding the role of smoking on non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). A few comments may be of interest. Full-Text PDF Open Access We appreciate the interest shown in our work by Drs. Babu and Paul. In their Letter to the Editor, they comment on a higher frequency of smoking reported by Athyros et al. among patients in the GREACE trial with presumed NAFLD compared to patients with normal liver tests [[1]Athyros V.G. Tziomalos K. Gossios D. et al.Safety and efficacy of long-term statin treatment for cardiovascular events in patients with coronary heart disease and abnormal liver tests in the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) Study: a post-hoc analysis.Lancet. 2010; 376: 1916-1922Abstract Full Text Full Text PDF PubMed Scopus (575) Google Scholar]. Interestingly, a previous study by Suzuki et al. also reported an association between current smoking and increase in serum ALT in subjects with presumed NAFLD [[2]Suzuki A. Lindor K. St. Saver J. et al.Effect of changes on body weight and lifestyle in nonalcoholic fatty liver disease.J Hepatol. 2011; 43: 1060-1066Abstract Full Text Full Text PDF Scopus (267) Google Scholar]. Drs. Babu and Paul point out that, fitting with our earlier report [[3]Zein C.O. Unalp A. Colving R. et al.Smoking and severity of hepatic fibrosis in nonalcoholic fatty liver disease.J Hepatol. 2011; 54: 753-759Abstract Full Text Full Text PDF PubMed Scopus (159) Google Scholar], a history of smoking was more frequent among subjects in the GREACE trial with presumed NAFLD compared to those with normal liver tests, and that in addition, current smoking was more frequent among subjects with presumed NAFLD compared to subjects with normal liver tests. These are interesting observations, and we agree with Drs. Babu and Paul that the available experimental and clinical evidence to date supports that smoking aggravates liver injury in NAFLD. However, although our conclusions and those of their analysis of the GREACE data undoubtedly point in the same direction, there are important differences between the observations of Drs. Babu and Paul and our original study. The report by Athyros et al. is based on a post hoc analysis of the GREACE trial data looking at the impact of treatment with statins on cardiovascular events in patients with mild to moderately elevated liver tests. The first important difference between the studies is that, as correctly stated by Drs. Babu and Paul in their letter, the GREACE trial used liver enzymes and ultrasound results as suggestive criteria for NAFLD diagnosis but lacked histopathological diagnosis confirmation and characterization. In contrast, the diagnosis of NAFLD in our cohort was well documented and characterized by histology. The second important difference is that our study aimed at investigating the association between smoking and severity of liver fibrosis in NAFLD in a cohort of NAFLD patients. In contrast, Drs. Babu and Paul looked at the frequency of smoking history and current smoking in patients in the GREACE trial with presumed NAFLD compared to those without NAFLD. These are fundamentally different comparisons. In conclusion, we agree with Drs. Babu and Paul and value their contribution to this important discussion. We support their opinion that smoking cessation should be recommended in patients with NAFLD. Future studies with careful prospective data collection on smoking and other predictors of disease severity in biopsy confirmed NAFLD are warranted. The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript. The underlying research reported in the study was funded by the National Institutes of Health grants to the NASH Clinical Research Network. Dr. Claudia O. Zein is supported by Grant No. KL2 RR024990 from the National Center for Research Resources, a component of the NIH Roadmap for Medical Research.