• Diana Barb, Fernando Bril, Srilaxmi Kalavalapalli, and Kenneth Cusi.
• Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Florida College of Medicine, Gainesville, Florida.
• J. Clin. Endocrinol. Metab. 2019 Aug 1; 104 (8): 3327-3336.

ContextThe relationship between plasma fibroblast growth factor 21 (FGF21), insulin resistance, and steatohepatitis has not been systematically assessed.ObjectiveTo determine if higher plasma FGF21 is associated with worse steatohepatitis on liver biopsy in patients with nonalcoholic fatty liver disease (NAFLD).Design And SettingCross-sectional study in a university hospital.Patients Interventions And Main Outcome MeasuresPatients with a body mass index >25 (n = 187) underwent: (i) euglycemic hyperinsulinemic clamp to assess tissue-specific insulin resistance (IR); (ii) liver magnetic resonance spectroscopy for intrahepatic triglyceride quantification, (iii) liver biopsy (if NAFLD present; n = 146); and (iv) fasting plasma FGF21 levels.Methods And ResultsPatients were divided into three groups: (i) No NAFLD (n = 41); (ii) No nonalcoholic steatohepatitis (NASH) (patients with isolated steatosis or borderline NASH; n = 52); and (iii) NASH (patients with definite NASH; n = 94). Groups were well-matched for age/sex, prevalence of type 2 diabetes mellitus, and hemoglobin A1c. During euglycemic hyperinsulinemic insulin clamp, insulin sensitivity in skeletal muscle and adipose tissue worsened from No NAFLD to NASH (both P < 0.001). Plasma FGF21 levels correlated inversely with insulin sensitivity in adipose tissue (r = -0.17, P = 0.006) and skeletal muscle (r = -0.23, P = 0.007), but not with liver insulin sensitivity. Plasma FGF21 was higher in patients with NASH (453 ± 262 pg/mL) when compared with the No NASH (341 ± 198 pg/mL, P = 0.03) or No NAFLD (325 ± 289 pg/mL, P = 0.02) groups. Plasma FGF21 increased with the severity of necroinflammation (P = 0.02), and most significantly with worse fibrosis (P < 0.001), but not with worsening steatosis (P = 0.60).ConclusionsPlasma FGF21 correlates with severity of steatohepatitis, in particular of fibrosis, in patients with NASH. Measurement of FGF21 may help identify patients at the highest risk of disease progression.Copyright © 2019 Endocrine Society.

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