Nonalcoholic Steatohepatitis (NASH) is one of the most common chronic liver diseases. The cause of NASH is not completely understood and currently there is no effective treatment for this disease. An effective approach to treatment is needed since without treatment this disease may progress to fibrosis and cirrhosis. Obesity is one of the most important risk factors for NASH and weight reduction is generally recommended as an initial step in its management. However, there has never been a randomized controlled trial evaluating the efficacy of weight reduction as a treatment for NASH. Data from uncontrolled trials using poorly defined primary outcome measures and patient populations and nonstandardized weight loss interventions suggest that modest weight loss may improve liver histology. The objective of this R03 application is to conduct a pilot study in preparation for a randomized controlled trial of weight reduction in the management of NASH. In the proposed pilot study, 20 overweight or obese individuals with biopsy-proven NASH will be enrolled to receive 48 weeks of intensive weight management using a combination of diet, exercise and behavior modification with a goal of 7-10% weight reduction. This weight loss program is similar to programs used successfully in other overweight populations and to the intensive lifestyle program of the Diabetes Prevention Progam and Look AHEAD. At the end of the 48-week study, patients will have a repeat liver biopsy that will be compared to their baseline biopsy. The pilot study will establish the feasibility of recruiting this population, producing sustained weight loss and performing repeat liver biopsies. It will also provide the data for a power analysis for a full-scale trial using changes in liver histology as the primary outcome measure. The proposed project represents an exciting collaboration between a new physician researcher with experience in NASH and a behavioral psychologist experienced in clinical trials of weight control. Based on the outcomes of this preliminary trial, this program will be further refined and readied for a larger-scale clinical trial.
| Promrat, Kittichai; Longato, Lisa; Wands, Jack R et al. (2011) Weight loss amelioration of non-alcoholic steatohepatitis linked to shifts in hepatic ceramide expression and serum ceramide levels. Hepatol Res 41:754-62 |
| Promrat, Kittichai; Kleiner, David E; Niemeier, Heather M et al. (2010) Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology 51:121-9 |
