Serum leptin levels, hepatic leptin receptor transcription, and clinical predictors of non-alcoholic steatohepatitis in obese bariatric surgery patients.

ABSTRACT

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a major cause of liver disease in morbidly obese patients. Clinical predictors of NASH remain elusive, as do molecular mechanisms of pathogenesis. METHODS: A series of 35 morbidly obese patients undergoing bariatric surgery had a liver biopsy performed for standard histologic analysis. In addition, RNA was obtained from liver tissue and analyzed for leptin receptor gene expression. Regression analysis was used to correlate clinical variables, including serum leptin levels and hepatic leptin receptor gene expression, with the presence of histologically confirmed NASH. RESULTS: Of the 35 subjects enrolled, 29% had steatosis only, 60% had NASH, and 11% had normal liver histology. Among the clinical variables studied, only diabetes mellitus was an independent predictor of NASH. There was a trend toward lower levels of mRNA encoding the long form of the leptin receptor in hepatic tissue from patients with NASH compared to those with steatosis only. CONCLUSIONS: Diabetes mellitus is associated with an increased risk of NASH in obese patients. Downregulation of hepatic leptin receptor may play a role in the pathogenesis of NASH.