title: Increased circulating zonulin in children with biopsy-proven nonalcoholic fatty liver disease.
abstract: OBJECTIVE
  To investigate the potential association of circulating zonulin with the stage of liver disease in obese children with biopsy-confirmed nonalcoholic fatty liver disease (NAFLD).
  
  
  METHODS
  A case-control study was performed. Cases were 40 obese children with NAFLD. The diagnosis of NAFLD was based on magnetic resonance imaging (MRI) with high hepatic fat fraction (HFF ≥ 5%), and confirmed by liver biopsy with ≥ 5% of hepatocytes containing macrovesicular fat. Controls were selected from obese children with normal levels of aminotransferases, and without MRI evidence of fatty liver as well as of other causes of chronic liver diseases. Controls were matched (1-to 1) with the cases on age, gender, pubertal stage and as closely as possible on body mass index- standard deviation score. All participants underwent clinical examination, laboratory tests including zonulin, inflammatory and metabolic parameters, and MRI for measurement of HFF and visceral adipose tissue.
  
  
  RESULTS
  Zonulin values were significantly greater in obese subjects with NAFLD than in those without NAFLD [median (interquartile range), 4.23 (3.18-5.89) vs 3.31 (2.05-4.63), P < 0.01]. In patients with NAFLD, zonulin concentrations increased significantly with the severity of steatosis and the Spearman's coefficient revealed a positive correlation between zonulin values and steatosis (r = 0.372, P < 0.05); however, we did not find a significant correlation between zonulin and lobular inflammation (P = 0.23), ballooning (P = 0.10), fibrosis score (P = 0.18), or presence of nonalcoholic steatohepatitis (P = 0.17). Within the entire study population, zonulin levels were positively associated with gamma-glutamyl transferase, 2-h insulin, HFF, and negatively associated with whole-body insulin sensitivity index (WBISI), after adjustment for age, gender and pubertal status. When the associations were restricted to the group of NAFLD patients, 2-h insulin, hepatic fat, and WBISI retained statistical significance.
  
  
  CONCLUSIONS
  Circulating zonulin is increased in children and adolescents with NAFLD and correlates with the severity of steatosis.
authors.affiliation: Lucia Pacifico, Sara Romaggioli, Stefano Bascetta, Department of Pediatrics and Child Neuropsychiatry, Sapienza University of Rome, 00161 Rome, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Pacifico
authors.affiliation: Lucia Pacifico, Sara Romaggioli, Stefano Bascetta, Department of Pediatrics and Child Neuropsychiatry, Sapienza University of Rome, 00161 Rome, Italy.
authors.forename: Enea
authors.initials: E
authors.lastname: Bonci
authors.affiliation: Lucia Pacifico, Sara Romaggioli, Stefano Bascetta, Department of Pediatrics and Child Neuropsychiatry, Sapienza University of Rome, 00161 Rome, Italy.
authors.forename: Lidia
authors.initials: L
authors.lastname: Marandola
authors.affiliation: Lucia Pacifico, Sara Romaggioli, Stefano Bascetta, Department of Pediatrics and Child Neuropsychiatry, Sapienza University of Rome, 00161 Rome, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Romaggioli
authors.affiliation: Lucia Pacifico, Sara Romaggioli, Stefano Bascetta, Department of Pediatrics and Child Neuropsychiatry, Sapienza University of Rome, 00161 Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Bascetta
authors.affiliation: Lucia Pacifico, Sara Romaggioli, Stefano Bascetta, Department of Pediatrics and Child Neuropsychiatry, Sapienza University of Rome, 00161 Rome, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Chiesa
mesh_terms: D000293:Adolescent; D000367:Age Factors; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D016022:Case-Control Studies; D002648:Child; D002772:Cholera Toxin / Q000097:blood*; D005260:Female; D006242:Haptoglobins; D006801:Humans; D008099:Liver / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000175:diagnosis* / Q000209:etiology / Q000473:pathology; D063766:Pediatric Obesity / Q000150:complications; D011237:Predictive Value of Tests; D011498:Protein Precursors; D012307:Risk Factors; D012720:Severity of Illness Index; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D006242:Haptoglobins; D011498:Protein Precursors; C408043:zonulin; D002772:Cholera Toxin
keywords: Children; Intestinal permeability; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; Zonulin