title: Loss of ileum decreases serum fibroblast growth factor 19 in relation to liver inflammation and fibrosis in pediatric onset intestinal failure.
abstract: OBJECTIVE
  The pathogenesis of intestinal failure (IF) associated liver disease (IFALD) is uncertain, we therefore investigated the role of FGF19 and pro-inflammatory cytokines has on this disease state.
  
  
  METHODS
  Serum FGF19, IL-6 and, TNF-α were measured in 52 IF patients at median age 6.0 years (IQR 2.2-13) after 10 months (4.1-39) on parenteral nutrition (PN). Thirty-nine patients underwent liver biopsies.
  
  
  RESULTS
  In IF patients, FGF19 concentrations were lower and those of IL-6 and TNF-α higher compared to healthy matched controls (p ⩽ 0.001 for all). FGF19 concentrations were further decreased in patients without a remaining ileum [37 pg/ml (IQR 30-68) vs. 74 (35-135) p=0.028], and correlated with remaining ileum length (r = 0.333, p = 0.018) and markers of cholesterol synthesis (r = -0.552 to -0.643, p < 0.001). Patients with histological portal inflammation [30 pg/ml (28-45) vs. 48 (33-100), p = 0.019] or fibrosis [35 pg/ml (30-66) vs. 99 (38-163), p = 0.013] had lower serum FGF19 concentrations than others. FGF19 negatively correlated with portal inflammation grade (r = -0.442, p = 0.005), serum TNF-α (r = -0.318, p = 0.025), METAVIR fibrosis stage (r = -0.441, p = 0.005) and APRI (r = -0.328, p = 0.028). IL-6 was higher during PN [6 pg/ml (2-31)] than after weaning off PN [2 pg/ml (1-5), p = 0.009], correlated weakly with cholestasis grade (r = 0.328, p = 0.044), and tended to associate with histological cholestasis [n = 5, 5 pg/ml (5-267) vs. n=34, 2 pg/ml (1-7), p = 0.058].
  
  
  CONCLUSIONS
  In pediatric onset of IF, total or partial loss of ileum decreases serum FGF19 concentration corresponding to hepatic inflammation and fibrosis, along with increased cholesterol synthesis. In contrast, serum IL-6 increases during PN and may associate with concurrent cholestasis. These data suggests that FGF19 may contribute to the pathogenesis of IFALD.
authors.affiliation: Section of Pediatric Surgery, Pediatric Liver and Gut Research Group Helsinki, Children's Hospital, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland. Electronic address: annika.mutanen@helsinki.fi.
authors.forename: Annika
authors.initials: A
authors.lastname: Mutanen
authors.affiliation: Department of Pathology, HUSLAB, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.
authors.forename: Jouko
authors.initials: J
authors.lastname: Lohi
authors.affiliation: Department of Pathology, HUSLAB, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.
authors.forename: Päivi
authors.initials: P
authors.lastname: Heikkilä
authors.affiliation: Department of Pediatric Nephrology and Transplantation, Children's Hospital, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.
authors.forename: Hannu
authors.initials: H
authors.lastname: Jalanko
authors.affiliation: Section of Pediatric Surgery, Pediatric Liver and Gut Research Group Helsinki, Children's Hospital, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.
authors.forename: Mikko P
authors.initials: MP
authors.lastname: Pakarinen
mesh_terms: D002648:Child; D002675:Child, Preschool; D002784:Cholesterol / Q000096:biosynthesis; D005260:Female; D005346:Fibroblast Growth Factors / Q000097:blood* / Q000172:deficiency; D006505:Hepatitis / Q000473:pathology; D006801:Humans; D007082:Ileum / Q000473:pathology*; D015850:Interleukin-6 / Q000097:blood; D007410:Intestinal Diseases / Q000097:blood* / Q000473:pathology*; D008099:Liver / Q000293:injuries / Q000473:pathology*; D008103:Liver Cirrhosis / Q000473:pathology; D008107:Liver Diseases / Q000097:blood / Q000209:etiology / Q000473:pathology; D008297:Male; D010288:Parenteral Nutrition; D012778:Short Bowel Syndrome / Q000150:complications; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: C117476:FGF19 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D005346:Fibroblast Growth Factors; D002784:Cholesterol
keywords: Bile acids; Interleukin-6; Liver disease; Parenteral nutrition; Tumor necrosis factor-α