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Adipose tissue contributes to nonalcoholic fatty liver disease (NAFLD), being a source of fatty acids and cytokines such as leptin and adiponectin, and regulating ghrelin production. Their role in NAFLD pathogenesis remains controversial. We aimed to study the influence of those cytokines on the severity of NAFLD.Morbidly obese individuals with biopsy-proven NAFLD were recruited. The NAFLD activity score was applied to liver histology. Serum concentrations of adiponectin, leptin, and ghrelin were determined.Eighty-two patients were included, 13% with nonalcoholic steatohepatitis (NASH). Hypertriglyceridemia (P=0.018) and metabolic syndrome (P=0.040) were independent factors associated with NASH. Leptin associated positively and ghrelin associated negatively with BMI; adiponectin associated negatively with the waist to hip ratio. Adiponectin associated negatively with insulin resistance, hypertension, and metabolic syndrome; ghrelin associated positively with diabetes mellitus. Adiponectin below 23 ng/ml associated with NASH (odds ratio 12.95, P<0.001). Leptin increased progressively (P=0.032) and adiponectin decreased (P=0.004) with increasing severity of steatosis. Also, leptin increased progressively with more severe fibrosis (P=0.053). A formula incorporating the three cytokines yielded an AUROC of 0.789 (P=0.002), a sensitivity of 81.8%, and a specificity of 76.1% for NASH.An imbalance in adiponectin, leptin, and ghrelin seems to be associated with more severe NAFLD. A formula combining the three cytokines showed good accuracy for NASH.