Author information
1 Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Florida College of Medicine, Gainesville, FL.
2 Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Malcom Randall Veterans Affairs Medical Center, Gainesville, Florida.
Abstract
CONTEXT:
The relationship between plasma FGF21, insulin resistance and steatohepatitis has not been systematically assessed.
OBJECTIVE:
To determine if higher plasma FGF21 is associated with worse steatohepatitis on liver biopsy in patients with NAFLD.
DESIGN AND SETTING:
Cross-sectional study in a University Hospital.Patients Interventions and Main Outcome MeasuresPatients with BMI>25 (n=187) underwent: (a) euglycemic hyperinsulinemic clamp to assess tissue specific insulin resistance; (b) liver magnetic resonance spectroscopy (1H-MRS) for intrahepatic triglyceride (IHTG) quantification, (c) liver biopsy (if NAFLD present; n=146); and (d) fasting plasma FGF21 levels.
METHODS AND RESULTS:
Patients were divided into three groups: (a) No NAFLD (n=41); (b) No NASH: patients with isolated steatosis or borderline NASH (n=52); and (c) NASH: patients with definite NASH (n=94). Groups were well-matched for age/gender, prevalence of T2DM and 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 to No NASH (341±198pg/ml, p=0.03) or No NAFLD (325±289 pg/ml, p=0.02). 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).
CONCLUSIONS:
Plasma 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.