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/m 2 . 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.)
Hepatocellular carcinoma is a significant cause of mortality worldwide and a growing problem in the United States. Treatment options are often limited, and median survival is less than 1 year. Thus, prevention may provide the best opportunity to alter the natural history of this disease. Primary prevention is best exemplified by the successes of such public health measures as universal hepatitis B vaccination. Such antiviral therapies as interferon may also have a role. Lessons can be learned from complementary and alternative medicine. Nevertheless, more work is needed in understanding hepatocarcinogenesis and in developing models to assess potential chemopreventive agents.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
334 Leonard St
Brooklyn, NY 11211
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.