Nonalcoholic steatohepatitis (NASH) is a chronic liver disease characterized by accumulation of fat in the liver accompanied by necroinflammation and hepatocellular injury(1). Despite being one of the most common chronic liver diseases in the U.S., there is currently no approved pharmacologic therapy for this condition(2). An effective medical treatment of NASH is clearly needed since without treatment this disease can progress to cirrhosis and liver failure in a significant proportion of cases(3). Several pharmaceutical interventions have been evaluated but none has been approved for general use(4, 5). Clinical trials of insulin-sensitizing agents such as thiazolidinediones have shown promising results(6-8) but side effects and the need for long term therapy may limit widespread acceptance(9). Obesity is considered one of the most important risk factors for this condition(10). Weight reduction is generally recommended as an initial step in the management of NASH(11). However, the efficacy of weight reduction for the treatment of NASH has not been carefully evaluated(12, 13). Prior studies of the effects of weight reduction on NASH have been uncontrolled, used poorly defined patient populations and non-standardized weight loss interventions, and lacked a well-accepted primary outcome for NASH(12, 13). The objective of this study was to conduct a randomized controlled trial of a year-long weight reduction in the management of NASH using a standardized state-of-the-art lifestyle intervention program. Overweight or obese individuals with biopsy-proven NASH were randomized to receive either standard medical care and educational sessions related to NASH, healthy eating, weight loss, and exercise (control group); or to an intensive weight management with a goal of at least 7-10 % weight reduction (lifestyle intervention group). The weight loss intervention was modeled on interventions that have been successful in other overweight populations(14) and was similar to the programs implemented in DPP (Diabetes Prevention Program)(15, 16) and Look AHEAD(17, 18), an ongoing study with overweight individuals with type 2 diabetes. We hypothesized that a 7-10% weight reduction through intensive lifestyle intervention would lead to improvements of biochemical and histological features of NASH. The primary outcome measure was improvement in NASH activity score (NAS) of at least 3 points or post treatment-NAS of 2 points or less.