J Gastrointestin Liver Dis, March 2017 Vol. 26 No 1: 1: 59-67 1) Faculty of Medicine, Al Azhar University, Cairo; 2) Ain Shams University, Faculty of Medicine; 3) Kasr-AlAiny Medical School, Cairo University; 4) Faculty of Pharmacy, Alexandria University; 5) Genetic Engineering & Biotechnology Research Institute, University of Sadat City; 6) Faculty of Veterinary Medicine, Cairo University; 7) Faculty of Medicine, Beni Suef University; 8) Department of Pharmaceutics and Pharmaceutical Sciences, Faculty of Pharmacy, Alexandria University, Egypt Address for correspondence: Ahmed Saber Elgebaly Faculty of Medicine, Al-Azhar University, Madinet Nasr, Abbassia, Cairo, Egypt Ahmedelgebaly94@azhar.edu.eg Received: 07.11.2016 Accepted: 25.02.2017 Resveratrol Supplementation in Patients with Non-Alcoholic Fatty Liver Disease: Systematic Review and Meta-analysis Ahmed Elgebaly 1 , Ibrahim A. I. Radwan 2 , Mohamed M. AboElnas 3 , Hamza H. Ibrahim 4 , Moutaz F. M. Eltoomy 5 , Ahmed A. Atta 6 , Hend A. Mesalam 1 , Alaa A. Sayed 7 , Amr A. Othman 8 INTRODUCTION Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease worldwide. It refers to a broad spectrum of liver diseases which vary from non- alcoholic steatohepatitis (NASH) to progressive fibrosis and cirrhosis with portal hypertension [1, 2]. Te clinical defnition of NAFLD depends on the presence of hepatic fat accumulation more than 5% of the liver weight and SYSTEMATIC REVIEW AND META-ANALYSIS ABSTRACT Background: Resveratrol is a potential treatment option for management of non-alcoholic fatty liver disease (NAFLD) due to its anti-infammatory, antioxidant properties, and calorie restriction-like efects. We aimed to synthesise evidence from published randomized clinical trials (RCTs) about the efcacy of resveratrol in the management of NAFLD. Methods: A computer literature search of PubMed, Scopus, Web of Science, and Cochrane Central was conducted using relevant keywords. Records were screened for eligible studies and data were extracted and synthesized using Review Manager Version 5.3 for windows. Subgroup analysis and sensitivity analysis were conducted. Results: Four RCTs (n=158 patients) were included in the fnal analysis. Te overall efect estimates did not favor resveratrol group in terms of: serum ALT (MD -2.89, 95%CI [-15.66, 9.88], p=0.66), serum AST (MD -3.59, 95%CI [-13.82, 6.63], p=0.49), weight (MD -0.18, 95%CI [-0.92, 0.55], p=0.63), BMI (MD -0.10, 95 %CI [-0.43, 0.24], p=0.57), blood glucose level (MD -0.27, 95%CI [-0.55, 0.01], p=0.05), insulin level (MD -0.12, 95%CI [-0.69, 0.46], p=0.69), triglyceride level (MD 0.04, 95%CI [-0.45, 0.53], p=0.87), and LDL level (MD 0.21, 95%CI [-0.41, 0.83], p=0.51). Pooled studies were heterogeneous. Conclusion: Current evidence is insufcient to support the efcacy of resveratrol in the management of NAFLD. Resveratrol does not attenuate the degree of liver fbrosis or show a signifcant decrease in any of its parameters. Key words: Non-alcoholic fatty liver disease – Resveratrol – steatosis – meta-analysis. Abbreviations: ALT: Alanine aminotransferase; AMPK: AMP-activated protein kinase; AST: Aspartate aminotransferase; BMI: Body mass index; CK-18: Cytokeratin-18; CRP: C-reactive protein; HC: Head circumference; HDL: High density lipoprotein; IL-6: Interleukin-6; LDL: Low density lipoprotein; MD: Mean diference; NAFLD: Non-alcoholic fatty liver disease; NASH: Non-alcoholic steatohepatitis; RCT: Randomized Controlled Trial; RR: Relative risk; SIRT1: Silent information regulation 2 homologue 1; TNF-α: Tumor necrosis factor α; WC: Waist circumference; WHR: Waist hip ratio. Available from: www.jgld.ro/wp/archive/y2017/n1/a12 DOI: http://dx.doi.org/10.15403/jgld.2014.1121.261.ely the exclusion of other causes of lipid infltration in the liver (absence of signifcant alcohol intake, hepatic viral infections, or other specifc causes of liver disease) [1]. Diferent theories have tried to identify the pathogenesis of progressive infammation and fbrosis in NAFLD. Previously, Day and colleagues proposed the “two-hit theory”, in which there is an impairment in fatty acid metabolism in hepatocytes, leading to a net accumulation of triglycerides within the liver, combined with peroxidation of lipid accumulated within hepatocytes [3]. Recently, Tilg and colleagues [4] suggested the “Multiple Parallel Hits Hypothesis” as a pathogenesis of NASH. Factors as excessive lipolysis, lipopolysaccharide accumulation in the liver, stimulation of Toll-like receptors, and endocrinal function of adipose tissue, are thought to be linked with the degree of steatosis and fbrosis [4].