Treatment of Non Alcoholic Fatty Liver Disease terol, and Insulin. All drugs had large effects on ALT and AST. In a Meta-analysis study to assess Metformin, eleven RCTs (671 participants, 27% diabetic; six RCTs in NASH with post-treatment histology, three with a low bias risk), the results showed that anorexigenic and weight-loss, de- creases gastrointestinal glucose absorption and increas- es insulin sensitivity, and AMP kinase-mediated oxidative glucose and lipid metabolism have been accrued in these patients. Liver histology compared to placebo was not improved but body weight, waist circumference, HOMA, FBS, HbA1c, increased HDL-C, and adiponectin significant- ly reduced (11). In one study, the effects of pioglitazone and placebo were examined on patients with NASH for a 12-month period and weight increase was observed in the group being treated with pioglitazone (12). In a Meta- analysis study about pioglitazone, results showed that pioglitazone did not further improve treatment of any diabetic patient with NASH, fatty liver, and liver histol- ogy. However HOMA and transaminases improved over two and three years, respectively (11). In present study a significant decrease was observed in mean fasting blood glucose and serum insulin level in all groups, and also differences in average changes were significant between the groups. The most reduction in blood glucose level was observed in pioglitazone group. The least decrease in blood sugar was observed in silymarin group and the dif- ference in average changes was significant between this and two other groups. In one study, there was no signifi- cant decrease in fasting blood glucose level before and after treatment with silymarin compared to placebo (13). However, in another study, silymarin was associated with decrease in resistance to insulin and serum insulin level in patients with cirrhosis and diabetes (14). Given the role played by pioglitazone and metformin in treatment of di- abetes, results obtained from the study were expectable but the noticeable point was the effect of silymarin on de- creasing blood sugar and insulin level, and HOMA index. In this study a significant reduction in serum choles- terol and triglyceride was observed in all three treatment groups. The most reduction in triglyceride was observed in pioglitazone group and the least average change was observed in silymarin group. The most reduction in cho- lesterol was observed in metformin group and difference in average changes in cholesterol also was not significant between pioglitazone and silymarin groups. In one study in Miami University of U.S.A comparing pioglitazone and placebo effects in patients with NASH, no changes were observed in lipid profile after the intervention (1). In the present study, decrease in AST and ALT levels was observed in all three groups but in silymarin group it was more than that of other groups. In previous studies, decrease in hepatic transaminases was reported after taking silymarin (13, 15, 16). In some studies on metfor- min and pioglitazone, decrease in hepatic transaminases level and histological improvement were reported in patients with NASH. In present study patients tolerated Hepat Mon. 2012;12(8):e6099 Hajiaghamohammadi AA et al. the drugs very well, and except for weight gain, no spe- cific disorders were observed in relation to pioglitazone drug, although due to cardiac side effect it is not an is- sue for long term treatment of NAFLD. The probability of weight gain increases with long-term consumption of pioglitazone which can lead to weakening of its ben- eficial effects on treatment of NAFLD and it seems that more studies in this field are necessary to conduct before recommending this drug. In summary, results show that all drugs decrease ALT and AST but pioglitazone and met- formin can reduce lipid profile as well as improve insu- lin and glucose parameters. Moreover, Silymarin is well tolerated and seems to be with no side effects when used for two months. Given the increasing incidence of non-al- coholic fatty liver disease and its subsequent outcomes in the form of cirrhosis and hepatocellular carcinoma and given the relationship between this disease and increase in resistance to insulin and oxidative stress, it seems nec- essary to conduct longer period studies on silymarin, metformin, and pioglitazone, and examine the effects of other antioxidants and drugs reducing resistance to in- sulin. Acknowledgements The authors thank the participants involved in this study and the Department of research of Qazvin Univer- sity of Medical Science for endorsing the project. Authors’ Contribution The work presented here was carried out in collabora- tion between all authors. AAH and AZ defined the re- search theme, carried out the laboratory experiments, discussed analyses, interpretation, and presentation. SO designed methods and experiments, analyzed the data, interpreted the results and wrote the paper. HM co-worked on associated data collection and their inter- pretation. All authors have contributed to, seen and ap- proved the manuscript. Financial Disclosure None declared. Funding/Support None declared. References 1. Al-Gharabally A, O’Brien CB, Acosta RC. A pilot study of pio- glitazon for treatment of non-alcholic fatty liver disease. Hepat Mon. 2007;7(3):131-7. 2. Serfaty L, Lemoine M. Definition and natural history of meta- bolic steatosis: clinical aspects of NAFLD, NASH and cirrhosis. Diabetes Metab. 2008;34(6 Pt 2):634-7. 3. Farrell GC, van Rooyen D, Gan L, Chitturi S. NASH is an Inflamma- tory Disorder: Pathogenic, Prognostic and Therapeutic Implica- tions. Gut Liver. 2012;6(2):149-71. 4. Glueck CJ, Moreira A, Goldenberg N, Sieve L, Wang P. Piogli- tazone and metformin in obese women with polycystic ovary 5