Our data suggest that overweight or obese patients with NASH can successfully achieve a weight reduction of 7% to 10% of initial body weight and maintain it through 1 year of study participation. In the current study, participants in the lifestyle selleck kinase inhibitor intervention group lost an average of 9.3% from baseline weight as compared with 0.2% in the control group. Importantly, the results from this study suggest that lifestyle modifications focusing on diet, exercise, and behavioral changes can successfully

lead to improvements in overall NASH histological activity, degree of steatosis, and liver chemistry. Published studies on weight reduction as a treatment for NASH have several major limitations.30, 31 Most notably, there has yet to be a rigorously conducted randomized controlled trial to address the efficacy of weight reduction in adult patients with NASH. Most published studies have been either small retrospective or prospective case series without inclusion of a comparison group.32, 33 Many studies did not stratify patients according to histological criteria34 and thus may have included not only patients with NASH but also patients with simple steatosis who have a different natural history and clinical outcomes. In addition, these studies used primary outcomes that are not well accepted, such as serum aminotransferases

or sonographic findings.35–38 Another important shortcoming of earlier studies is that they used weight reduction strategies such as prolonged fasting39 or very-low-calorie AZD5363 dieting40 that cannot be sustained over a long period. Several recent pharmaceutical trials for NASH have included dietary intervention for comparison.8, 41 Although the effects www.selleck.co.jp/products/lonafarnib-sch66336.html of nutritional counseling in these studies appeared to be inferior to the investigational drugs, these dietary interventions produced minimal or no weight loss and thus cannot address the question of whether weight loss leads to improvements in NASH. This study had a number of strengths, including

the selection of patients with well-characterized NASH both clinically and histologically, the randomized design, the high completion rate (97%, only one dropout), and the use of the current histological scoring criteria by NASH Clinical Research Network. In addition, our study used a standardized, protocol-based lifestyle intervention similar to the programs implemented in the Diabetes Prevention Program15 and Look AHEAD, an ongoing study with overweight individuals with type 2 diabetes.18 The effect sizes for overall NASH disease activity (Cohen’s d = .82) and steatosis (Cohen’s d = .97) were large, and thus differences between lifestyle and control were statistically significant even with the relatively small sample size.