Orlistat for overweight subjects with nonalcoholic steatohepatitis: A randomized, prospective trial

Abstract

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.)

The diagnosis and management of non-alcoholic fatty liver disease: Practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association

“…7% weight loss had significant improvement in steatosis, lobular inflammation, ballooning, and NAFLD Activity Score (NAS). 101 There was a similar pattern in the study by Harrison et al, 100 where participants who lost > 5% body weight improved steatosis, whereas individuals with ! 9% weight loss had significant improvement in steatosis, lobular inflammation, ballooning, and NAS.…”

“…In the study by ZieglerSagi et al, 99 orlistat reportedly improved ALT and steatosis by US, but its effect on liver histology could not be evaluated because the majority of patients did not undergo a follow-up liver biopsy. However, in the study by Harrison et al, 100 orlistat did not improve body weight or liver histology.…”

Impact of current treatments on liver disease, glucose metabolism and cardiovascular risk in non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of randomised trials

“…Two RCTs also showed an improvement in plasma adiponectin [8,12]. Among drugs inducing weight loss, orlistat was safe, well-tolerated with minor adverse gastrointestinal complaints not requiring discontinuation of therapy, but conferred no additional cardio-metabolic or histological benefit over lifestyle intervention alone [7,12].…”

“…Eight RCTs (373 participants, 39% diabetic; six RCTs with a low risk of bias, four RCTs with post-treatment histology) assessed the effect of lifestyle-or drug-induced weight loss in NAFLD [6][7][8][9][10][11][12][13] (ESM Table 1). …”

EASL–EASD–EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease

“…Available data on pentoxifylline and orlistat are limited or inconclusive [86,91,97]. Also, data on lipidlowering drugs are poor; recent trials with ezetimibe were negative [101,103], whereas statins have not been adequately tested.…”