title: Portal inflammation is independently associated with fibrosis and metabolic syndrome in pediatric nonalcoholic fatty liver disease.
abstract: Pediatric nonalcoholic fatty liver disease (NAFLD) histology demonstrates variable amounts of portal inflammation, which may be associated with more severe liver disease and fibrosis. We assessed the relationship between portal inflammation, hepatic fibrosis, and the metabolic syndrome in pediatric NAFLD. Children with biopsy-proven NAFLD were eligible for inclusion. Histology was assessed using Kleiner fibrosis stage and the Nonalcoholic Steatohepatitis Clinical Research Network system for portal inflammation. Patients were divided by histology into type 1, type 2, and overlap NAFLD. Multivariable ordinal logistic regression was used to determine factors associated with fibrosis and portal inflammation. The 430 Caucasian children were divided into 52 with type 1, 95 with type 2, and 283 with overlap NAFLD. Those with type 2 had a more severe metabolic phenotype, with higher body mass index z score (2.0 versus 1.6, P < 0.0001), waist circumference centile (96th versus 90th, P < 0.0001), and triglycerides (84 versus 77 mg/dL, P = 0.01) and lower high-density lipoprotein (46 versus 60 mg/dL, P = 0.004) than those with type 1. Similarly, those with overlap NAFLD had a more severe phenotype. Stage 2-3 fibrosis was present in 69/283 (24%) with overlap NAFLD. Portal inflammation was associated with stage 2-3 fibrosis on multivariable analysis (95% confidence interval 1.4-5.2, odds ratio = 3.7). Waist circumference centile was associated with portal inflammation (95% confidence interval 1.2-3.4, odds ratio = 2.0).
  
  
  CONCLUSIONS
  Portal inflammation is associated with more advanced pediatric NAFLD and features of the metabolic syndrome.
authors.affiliation: Department of Paediatrics, University of Cambridge, Cambridge, UK.
authors.forename: Jake P
authors.initials: JP
authors.lastname: Mann
authors.affiliation: Histopathology Unit, Bambino Gesu Hospital, IRCCS, Rome, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: De Vito
authors.affiliation: Hepatometabolic Unit, Bambino Gesu Hospital, IRCCS, Rome, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Mosca
authors.affiliation: Liver Research Unit, Bambino Gesu Hospital, IRCCS, Rome, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Alisi
authors.affiliation: National Institute for Health Research, Birmingham Liver Biomedical Research Unit and Centre for Liver Research, University of Birmingham, Birmingham, UK.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Armstrong
authors.affiliation: Medical Directorate, Bambino Gesu Hospital, IRCCS, Rome, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Raponi
authors.affiliation: Paediatric Gastroenterology and Hepatology, Children's Hospital, Hannover Medical School, Hannover, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Baumann
authors.affiliation: Hepatometabolic Unit, Bambino Gesu Hospital, IRCCS, Rome, Italy.|Liver Research Unit, Bambino Gesu Hospital, IRCCS, Rome, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: Nobili
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D005355:Fibrosis; D006801:Humans; D008099:Liver / Q000473:pathology*; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications*; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D011169:Portal Vein / Q000276:immunology / Q000473:pathology*