Serum FGF21 increases with hepatic fat accumulation in pediatric onset intestinal failure

Abstract

Background & aims: Previously, FGF21 has been related to glucose and lipid metabolism and liver steatosis. Our aim was to evaluate serum FGF21 levels in pediatric onset intestinal failure (IF).

Methods: Serum FGF21 was measured in 35 IF patients at median age of 7.8 years (range 0.2-27) and 59 matched healthy controls. Thirty patients underwent liver biopsy.

Results: Serum FGF21 levels were increased in patients compared to controls [229 pg/ml (21-20,345) vs. 133 pg/ml (7-1607), p=0.018]. Frequency of liver steatosis (60% vs. 50%, p=0.709) was similar during (6/10) and after (10/20) weaning off parenteral nutrition (PN). Patients with steatosis had markedly higher serum FGF21 concentration [626 pg/ml (21-20,345) vs. 108 pg/ml (32-568), p=0.002] and more advanced liver fibrosis [Metavir stage 1.6 (0-4) vs. 0.7 (0-3), p=0.020] without associated inflammation or Mallory body formation. Serum FGF21 levels reflected the degree of steatosis [FGF21 in grade 3 vs. grades 0-2, p<0.001; grade 1 vs. controls, p=0.002], and correlated with steatosis grade (r=0.589, p=0.001). Hepatic steatosis and serum FGF21 showed similar associations with duration of PN and remaining small bowel length (p<0.05 for all). In a multivariate regression model, liver steatosis grade (β=0.630, p=0.001) predicted serum FGF21 concentration.

Conclusions: In pediatric IF increased serum FGF21 levels reflect liver steatosis, while both are exclusively associated with duration of PN and extent of small intestinal resection. Liver steatosis is coupled with progression of fibrosis without accompanying inflammation. Serum FGF21 assay may be useful for diagnosing liver steatosis in IF patients.

Keywords: ALT; APRI; AST; AST-to-platelet ratio index; BMI; Children; FGF21; GT; Glucose homeostasis; HDL; HOMA-IR; HbA1c; IF; IFALD; INR; ISO-BMI; Intestinal failure; LDL; Liver steatosis; NASH; P-TT; PN; Serum lipids; alanine aminotransferase; aspartate aminotransferase; body mass index; body mass index-for-age; fibroblast growth factor 21; glutamyl transferase; glycosylated hemoglobin; high-density lipoprotein; homeostasis model assessment; international normalized ratio; intestinal failure; intestinal failure associated liver disease; low-density lipoprotein; nonalcoholic steatohepatitis; parenteral nutrition; plasma tromboplastin time.