title: Early interplay of intra-hepatic iron and insulin resistance in children with non-alcoholic fatty liver disease.
abstract: OBJECTIVE
  The liver is a crucial organ at the crossroads of iron and glucose metabolism. The aim of the study was to assess intra-hepatic iron in young patients with non-alcoholic fatty liver disease (NAFLD) and its association with insulin resistance and severity of liver damage.
  
  
  METHODS
  Intrahepatic iron content was assessed (Pearl's stain grade) in 66 patients (41 males, age 3.3-17.6years) with biopsy-proven NAFLD. Mutations of the Hereditary Hemochromatosis (HFE) gene were determined by sequence allele-specific polymerase chain reaction. Insulin resistance was estimated by means of the Oral Glucose Tolerance Test and the Insulin Sensitivity Index (ISI); the Insulino-Genic Index was also calculated. Tumor necrosis factor-alpha and interleukin-6 were measured.
  
  
  RESULTS
  Low-mild intra-hepatic iron deposition was observed in one out of five children (n=15, 22%), and it was not associated with HFE mutations, carried by 17 patients (26%). Among carriers of HFE mutations, four had siderosis. No abnormalities were observed in systemic indices of iron balance. Serum ferritin was within normal adult ranges in all patients (33.6±7.6ng/ml), but it was correlated with ISI (r(o)=-0.361; p=0.003). No significant difference was observed in insulin sensitivity, iron balance, inflammatory milieu, and liver histology between patients with and without hepatic siderosis.
  
  
  CONCLUSIONS
  In young obese individuals with NAFLD, despite normal peripheral iron parameters, mild intra-hepatic iron deposition is a frequent finding, but it is not associated with insulin resistance or severity of liver damage. Longitudinal studies are required to define the long-term relevance of these findings.
authors.affiliation: Laboratorio di Malattie Epatiche Auto-Immuni e Metaboliche, Ospedale Pediatrico Bambino Gesù, IRCCS, Roma, Italy. Electronic address: melania.manco@opbg.net.
authors.forename: Melania
authors.initials: M
authors.lastname: Manco
authors.affiliation: Laboratorio di Malattie Epatiche Auto-Immuni e Metaboliche, Ospedale Pediatrico Bambino Gesù, IRCCS, Roma, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Alisi
authors.affiliation: Section of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomédica de Girona and CIBER Fisiopatología de la Obesidad y Nutrición, Girona, Spain.
authors.forename: Jose-Manuel Fernandez
authors.initials: JF
authors.lastname: Real
authors.affiliation: Unità di Medicina Trasfusionale ed Immuno-Ematologia, Ospedale Santa Maria Goretti, Latina, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Equitani
authors.affiliation: Laboratorio di Malattie Epatiche Auto-Immuni e Metaboliche, Ospedale Pediatrico Bambino Gesù, IRCCS, Roma, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: DeVito
authors.affiliation: Dipartimento di Medicina Interna, Università degli Studi di Milano, Ospedale Maggiore "Ca' Granda", IRCCS, Milano, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Valenti
authors.affiliation: Laboratorio di Malattie Epatiche Auto-Immuni e Metaboliche, Ospedale Pediatrico Bambino Gesù, IRCCS, Roma, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: Nobili
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005234:Fatty Liver / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005293:Ferritins / Q000097:blood; D005951:Glucose Tolerance Test; D000071020:Hemochromatosis Protein; D006486:Hemosiderosis / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D007333:Insulin Resistance; D007501:Iron / Q000378:metabolism*; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D065626:Non-alcoholic Fatty Liver Disease
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D005293:Ferritins; D007501:Iron