Increased serum FGF21 levels in patients with nonalcoholic fatty liver disease

BACKGROUND: The fibroblast growth factor 21 (FGF21) hormonal pathway is a metabolic signalling cascade and has been recently identified as the master hormonal regulator of glucose, lipids and overall energy balance. In this observational, case-control study, we assayed serum levels of FGF21 in patients with nonalcoholic fatty liver disease (NAFLD), a hepatic manifestation of the metabolic syndrome, and examined their association with clinical, biochemical and histological phenotypes. MATERIALS AND METHODS: Serum levels of FGF21 were assayed by ELISA in 82 patients with biopsy-proven NAFLD and 77 controls. We analysed associations between FGF21 and the characteristics of patients with NAFLD by multiple linear regression analysis. RESULTS: Levels of FGF21 were significantly higher in patients with NAFLD (median 200 pg mL(-1) ; interquartile range: 87-410 pg mL(-1)) than in healthy controls (median 93 pg mL(-1) ; interquartile range: 70-180 pg mL(-1) , Mann-Whitney U-test, P<0·001). There was a stepwise increase in serum FGF21 levels according to the liver steatosis score (median level in subjects with score 1: 170 pg mL(-1) ; score 2: 220 pg mL(-1) ; score 3: 280 pg mL(-1) , P for trend <0·01). After stepwise linear regression analysis, serum FGF21 levels were the only independent predictor of hepatic steatosis scores in patients with NAFLD (β=0·26; t=2·659, P<0·01). CONCLUSIONS: Serum FGF21 levels are increased in patients with NAFLD regardless of potential confounders and represent an independent predictor of liver steatosis. These findings support further investigation of this molecule in metabolic liver diseases.