Intestinal failure to produce FGF19: A culprit in intestinal failure-associated liver disease?

K.J. van Erpecum*, Frank G. Schaap

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background & Aims: 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-alpha 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-alpha 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-alpha (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. (C) 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Original languageEnglish
Pages (from-to)1231-1233
JournalJournal of Hepatology
Volume62
Issue number6
DOIs
Publication statusPublished - 1 Jan 2015

Cite this