Annika Mutanen1, Jouko Lohi2, Päivi Heikkilä2, Hannu Jalanko3, Mikko P Pakarinen4. 1. 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. 2. Department of Pathology, HUSLAB, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland. 3. Department of Pediatric Nephrology and Transplantation, Children's Hospital, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland. 4. Section of Pediatric Surgery, Pediatric Liver and Gut Research Group Helsinki, Children's Hospital, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.
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-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.
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-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: Katharina Brandl; Phillipp Hartmann; Lily J Jih; Donald P Pizzo; Josepmaria Argemi; Meritxell Ventura-Cots; Sally Coulter; Christopher Liddle; Lei Ling; Stephen J Rossi; Alex M DePaoli; Rohit Loomba; Wajahat Z Mehal; Derrick E Fouts; Michael R Lucey; Francisco Bosques-Padilla; Philippe Mathurin; Alexander Louvet; Guadalupe Garcia-Tsao; Elizabeth C Verna; Juan G Abraldes; Robert S Brown; Victor Vargas; Jose Altamirano; Juan Caballería; Debbie Shawcross; Peter Stärkel; Samuel B Ho; Ramon Bataller; Bernd Schnabl Journal: J Hepatol Date: 2018-04-12 Impact factor: 25.083
Authors: Naureen Memon; Ian J Griffin; Chris W Lee; Aimee Herdt; Barry I Weinberger; Thomas Hegyi; Mary O Carayannopoulos; Lauren M Aleksunes; Grace L Guo Journal: J Matern Fetal Neonatal Med Date: 2018-10-29