Leptin, insulin resistance, and liver fibrosis in human nonalcoholic fatty liver disease

Data from animal models of fibrosis and fatty liver suggest that leptin may mediate the profibrogenic responses in the liver, but the association of leptin and liver fibrosis in human nonalcoholic fatty liver disease (NAFLD) remains undefined. We aimed at determining the relation between leptin and liver fibrosis in human NAFLD. Human plasma leptin and several indicators of insulin resistance were measured in 88 NAFLD patients and matched controls. Leptin levels were significantly greater in patients with more advanced fibrosis (P=0.005). By multivariate analysis, the significant association between leptin and fibrosis was abolished (adjusted P=0.3) when controlling for confounders including age, gender, BMI, diabetes and insulin resistance. Only age (adjusted P=0.006) and insulin sensitivity (adjusted P=0.04) correlated significantly with fibrosis stage. A second liver biopsy was performed in 39 out of the 88 patients at 27.9±16 months. Leptin levels were not significantly different between patients who had fibrosis progression (n=10) and those who did not (n=29). In human NAFLD, no relationship between leptin levels and fibrosis stage was demonstrated. The correlation of leptin and fibrosis severity seems to be an indicator of the factors that determine leptin production.