Smoking and non-alcoholic steatohepatitis (NASH): The GREek Atorvastatin and Coronary heart disease Evaluation (GREACE) trial
Authors: Niki Katsiki, Vasilios G. Athyros, Asterios Karagiannis, Dimitri P. Mikhailidis
Journal: Journal of Hepatology (2012)

As the authors of the GREek Atorvastatin and Coronary heart disease Evaluation (GREACE) trial [[1]Athyros V.G. Tziomalos K. Gossios T.D. Griva T. Anagnostis P. Kargiotis K. et al.GREACE Study Collaborative Group. 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 (516) Google Scholar], we appreciate the comments made by Babu et al. [[2]Babu M. Paul N. Smoking and NASH: a hidden message from the GREACE trial.J Hepatol. 2012; 56: 300-301Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar] and Zein et al. [[3]Zein C.O. McCullough A.J. Reply to: smoking and NASH: a hidden message from the GREACE trial.J Hepatol. 2012; 56: 301Abstract Full Text Full Text PDF Scopus (2) Google Scholar] regarding the role of smoking on non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). A few comments may be of interest. First, we assessed changes in vascular risk and the safety of statins [[1]Athyros V.G. Tziomalos K. Gossios T.D. Griva T. Anagnostis P. Kargiotis K. et al.GREACE Study Collaborative Group. 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 (516) Google Scholar]. We could not analyse every possible relationship. Second, in order to interpret the results of GREACE in terms of NAFLD/NASH, there is a need to know how many patients were smokers at the end of this trial. Essentially, the numbers were similar to baseline values. Third, it would be interesting to know the transaminase status at the end of the GREACE study. In the NAFLD + not on statin group, alanine aminotransferase (ALT) activity in smokers (n = 19) was 70 ± 7 vs. 61 ± 9 U/L in non-smokers (n = 191), p<0.0001. Therefore, smokers maintained a raised ALT activity over the 3-year duration of the trial. In the NAFLD + on statin group, ALT activity in smokers (n = 23) was 37 ± 6 vs. 37 ± 5 U/L in non-smokers (n = 204), p = 0.10. This suggests that statins improved ALT activity in smokers. These findings are limited because they are based on a post hoc analysis and the number of patients is small. Our findings support the hypothesis discussed by Babu et al. [[2]Babu M. Paul N. Smoking and NASH: a hidden message from the GREACE trial.J Hepatol. 2012; 56: 300-301Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar] and Zein et al. [[3]Zein C.O. McCullough A.J. Reply to: smoking and NASH: a hidden message from the GREACE trial.J Hepatol. 2012; 56: 301Abstract Full Text Full Text PDF Scopus (2) Google Scholar] regarding the adverse effect of smoking on NAFLD and NASH. More work is needed in this field. This letter was written independently. The authors did not receive financial or professional help with the preparation of the manuscript. DPM has given talks, attended conferences, and participated in advisory boards and trials sponsored by various pharmaceutical companies (MSD, Genzyme, and Abbott). 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 AccessReply to: "Smoking and NASH: A hidden message from the GREACE trial"Journal of HepatologyVol. 56Issue 1PreviewWe 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]. 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]. Drs. Babu and Paul point out that, fitting with our earlier report [3], 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. Full-Text PDF Open Access