title: Insulin-like growth factor-I and -II levels are associated with the progression of nonalcoholic fatty liver disease in obese children.
abstract: OBJECTIVE
  To correlate circulating levels of insulin-like growth factor (IGF)-I, IGF-II, and IGF binding protein (IGFBP)-3 in a population of obese children with biopsy-proven nonalcoholic fatty liver disease (NAFLD) with clinical, biochemical, and histological features.
  
  
  METHODS
  We conducted a cross-sectional study at the Hepatometabolic Unit of the Bambino Gesù Children's Hospital, Rome, Italy. Obese children (42 girls and 57 boys) underwent liver biopsy, anthropometry, biochemical assessment, and IGF system evaluation. Serum concentrations of IGF-I, IGF-II, and IGFBP-3 were measured. The liver biopsy features of each case were graded according to the NAFLD Activity Scoring system. The degrees of steatosis, inflammation, ballooning, and fibrosis were calculated.
  
  
  RESULTS
  Nonalcoholic steatohepatitis was diagnosed in 14/99 obese subjects. Stepwise regression analysis revealed that IGF-I was the major predictor of ballooning (β = -0.463; P < .0001) and NAFLD activity score (β = -0.457; P < .0001), IGF-I/IGFBP-3 ratio was the major predictor of liver inflammation (β = -0.285; P = .005), and IGF-II was the major predictor of liver fibrosis (β = 0.343; P < .005).
  
  
  CONCLUSIONS
  Circulating levels of IGF-I and IGF-II are associated with the histological stages of NAFLD and may represent novel markers of liver damage progression in obese children.
authors.affiliation: Department of Pediatrics, University Hospital, Bambino Gesù Children's Hospital, Tor Vergata University, Rome, Italy; Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden. Electronic address: stefano.cianfarani@opbg.net.
authors.forename: Stefano
authors.initials: S
authors.lastname: Cianfarani
authors.affiliation: Department of Pediatrics, University Hospital, Bambino Gesù Children's Hospital, Tor Vergata University, Rome, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Inzaghi
authors.affiliation: Hepatometabolic Disease Unit, Bambino Gesù Children's Hospital, Rome, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Alisi
authors.affiliation: Department of Systems Medicine, Tor Vergata University, Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Germani
authors.affiliation: Department of Systems Medicine, Tor Vergata University, Rome, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Puglianiello
authors.affiliation: Hepatometabolic Disease Unit, Bambino Gesù Children's Hospital, Rome, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: Nobili
mesh_terms: D015415:Biomarkers / Q000097:blood*; D001706:Biopsy; D002648:Child; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005234:Fatty Liver / Q000175:diagnosis* / Q000378:metabolism; D005260:Female; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D008099:Liver / Q000473:pathology; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease; D063766:Pediatric Obesity / Q000175:diagnosis* / Q000378:metabolism; D012044:Regression Analysis
chemical_list: D015415:Biomarkers; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II