Steatohepatitis/Metabolic Liver Disease
Article first published online: 22 OCT 2008
Copyright © 2008 American Association for the Study of Liver Diseases
Volume 49, Issue 1, pages 80–86, January 2009
How to Cite
Harrison, S. A., Fecht, W., Brunt, E. M. and Neuschwander-Tetri, B. A. (2009), Orlistat for overweight subjects with nonalcoholic steatohepatitis: A randomized, prospective trial. Hepatology, 49: 80–86. doi: 10.1002/hep.22575
Clinical Trials Government Study Number: NCT00160407.
Disclaimer statement: The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or reflecting the view of the Department of the Army or the Department of Defense.
Potential conflict of interest: Nothing to report.
- Issue published online: 28 DEC 2008
- Article first published online: 22 OCT 2008
- Accepted manuscript online: 22 OCT 2008 12:00AM EST
- Manuscript Accepted: 6 AUG 2008
- Manuscript Received: 30 JUL 2008
The aim of this study was to determine if orlistat, an inhibitor of fat absorption, combined with caloric restriction in overweight subjects with nonalcoholic steatohepatitis results in weight loss and improved liver histology. Fifty overweight subjects (body mass index = ≥27) with biopsy proven nonalcoholic steatohepatitis were randomized to receive a 1,400 Kcal/day diet plus vitamin E (800 IU) daily with or without orlistat (120 mg three times a day) for 36 weeks. Liver biopsies were repeated at week 36. Twenty-three subjects in the orlistat/diet/vitamin E group and 18 in the diet/vitamin E group completed the study. The mean age was 47 ± 9.0 (standard deviation) years and mean body mass index was 36.4 ± 6.3 kg/m2. Four subjects were diabetic. The orlistat group lost a mean of 8.3% body weight compared to 6.0% in the diet plus vitamin E group (not significant). Both groups also had similarly improved serum aminotransferases, hepatic steatosis, necroinflammation, ballooning, and nonalcoholic fatty liver disease activity scores. Stratified according to weight loss instead of treatment group, a loss of ≥5% body weight (n = 24) compared to <5% body weight (n = 17) correlated with improvement in insulin sensitivity (P = 0.001) and steatosis (P = 0.015). Comparing subjects who lost ≥9% of body weight (n = 16), to those that did not (n = 25), improved insulin sensitivity (P < 0.001), adiponectin (P = 0.03), steatosis (P = 0.005), ballooning (P = 0.04), inflammation (P = 0.045), and nonalcoholic fatty liver disease activity score (P = 0.009) were seen. Increases in adiponectin strongly correlated with improved ballooning and nonalcoholic fatty liver disease activity score (P = 0.03). Orlistat did not enhance weight loss or improve liver enzymes, measures of insulin resistance, and histopathology. However, subjects who lost ≥5% of body weight over 9 months improved insulin resistance and steatosis, and those subjects who lost ≥9% also achieved improved hepatic histologic changes. (HEPATOLOGY > 2009;49:80-86.)