Insulin-Like Growth Factor-I and -II Levels Are Associated with the Progression of Nonalcoholic Fatty Liver Disease in Obese Children

• Published in: The Journal of pediatrics Vol. 165; no. 1; pp. 92 - 98
• Main Authors: Cianfarani, Stefano, Inzaghi, Elena, Alisi, Anna, Germani, Daniela, Puglianiello, Antonella, Nobili, Valerio
• Format: Journal Article
• Language: English
• Published: United States Mosby, Inc 01.07.2014
• Subjects: Biomarkers - blood; Biopsy; Child; Cross-Sectional Studies; Disease Progression; Fatty Liver - diagnosis; Fatty Liver - metabolism; Female; Humans; Insulin-Like Growth Factor Binding Protein 3 - blood; Insulin-Like Growth Factor I - metabolism; Insulin-Like Growth Factor II - metabolism; Liver - pathology; Male; Non-alcoholic Fatty Liver Disease; Pediatric Obesity - diagnosis; Pediatric Obesity - metabolism; Pediatrics; Regression Analysis; CRP; GH; NAS; NAFLD; IL; IGF; IR; NASH; WC; TNF; apoB; IGFBP; HOMA-IR; CV; OGTT; ISI; BMI; Oral glucose tolerance test; C-reactive protein; Interleukin; Insulin-like growth factor; Coefficient of variation; Apolipoprotein B; Nonalcoholic fatty liver disease activity score; Body mass index; Nonalcoholic steatohepatitis; Nonalcoholic fatty liver disease; Insulin receptor; Insulin-like growth factor binding protein; Insulin sensitivity index; Waist circumference; Homeostasis model assessment for insulin resistance; Tumor necrosis factor; Growth hormone
• ISSN: 0022-3476; 1097-6833; 1097-6833
• DOI: 10.1016/j.jpeds.2014.01.052

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. 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. 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). 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.