The association of leptin with severity of non-alcoholic fatty liver disease: A population-based study

Background/Aims: Leptin is associated with metabolic disorders, which predispose one to non-alcoholic fatty liver disease (NAFLD). The role of leptin in NAFLD pathogenesis is not fully understood. We aim to investigate the association between serum leptin level and severity of NAFLD using U.S. nationally representative data. Methods: Data were obtained from the United States Third National Health and Nutrition Examination Survey. NAFLD was defined by ultrasound detection and severity of hepatic steatosis in the absence of other liver diseases. The severity of hepatic fibrosis was determined by NAFLD fibrosis score (NFS). We used multivariate survey-weighted generalized logistic regression to evaluate the association between leptin level and the degree of NAFLD. We also performed subgroup analyses by body mass index (lean vs. classic NAFLD). Results: Among 4,571 people, 1,610 (35%) had NAFLD. By ultrasound findings, there were 621 people with mild, 664 with moderate, and 325 with severe steatosis. There were 885 people with low NFS (<-1.455, no significant fibrosis), 596 with intermediate NFS, and 129 with high NFS (>0.676, advanced fibrosis). Leptin levels for normal, mild, moderate and severe steatosis were $10.7{\pm}0.3ng/mL$, $12.1{\pm}0.7ng/mL$, $15.6{\pm}0.8ng/mL$, $16{\pm}1.0ng/mL$, respectively (trend P-value<0.001). Leptin levels for low, intermediate, and high NFS were $11.8{\pm}0.5ng/mL$, $15.6{\pm}0.8ng/mL$, $28.5{\pm}3.5ng/mL$, respectively (trend P-value<0.001). This association remained significant even after adjusting for known demographic and metabolic risk factors. In the subgroup analysis, this association was only prominent in classic NAFLD, but not in lean NAFLD. Conclusions: Serum leptin level is associated with the severity of NAFLD, especially in classic NAFLD patients.