title: High Prevalence of Nonalcoholic Fatty Liver Disease in Adolescents Undergoing Bariatric Surgery.
abstract: OBJECTIVE
  Little is known about the prevalence of nonalcoholic fatty liver disease (NAFLD) among severely obese adolescents or factors that determine its development. We investigated the prevalence of NAFLD in a multicenter cohort of adolescents undergoing bariatric surgery and the factors associated with it.
  
  
  METHODS
  We enrolled 242 adolescents undergoing bariatric surgery between March 2007 and February 2012 at 5 tertiary care centers into a multicenter, prospective observational cohort study. Intraoperative core liver biopsies were collected from 165 subjects; 17 were excluded because of insufficient liver tissue or use of hepatotoxic medications, so 148 remained in the study (mean age, 16.8 ± 1.6 years; median body mass index = 52 kg/m(2)). Liver tissues were analyzed by histology using validated criteria. Hepatic gene expression was analyzed in 67 samples.
  
  
  RESULTS
  NAFLD was present in 59% of this predominantly female (72%), white (68%), non-Hispanic (91%) cohort. Of subjects with NAFLD, 24% had borderline and 10% had definite nonalcoholic steatohepatitis (NASH). Mild fibrosis (stage 2 or lower) was observed in 18% of liver biopsies and stage 3 was observed in 0.7%, but cirrhosis was not detected. Dyslipidemia was present in 78% of subjects, hypertension in 44%, and diabetes in 14%. More severe NAFLD was associated with increasing levels of alanine aminotransferase, fasting glucose level, hypertension (each P < .01), and white blood cell count (P = .04). Only diabetes was associated with detection of fibrosis (odds ratio = 3.56; 95% confidence interval: 1.93-6.56). Microarray analysis associated presence of NASH with altered expression of genes that regulate macrophage chemotaxis, cholesterol absorption, and fatty acid binding.
  
  
  CONCLUSIONS
  More than half of adolescents undergoing bariatric surgery in this cohort had NAFLD, yet the prevalence of severe or fibrotic NASH was low. Increasing severity of NAFLD was associated with level of alanine aminotransferase and cardiometabolic risk factors, but not body mass index. Based on gene expression analysis, borderline and definite NASH were associated with abnormal immune function, intestinal cholesterol absorption, and lipid metabolism.
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio. Electronic address: Stavra.xanthakos@cchmc.org.
authors.forename: Stavra A
authors.initials: SA
authors.lastname: Xanthakos
authors.affiliation: Division of Pediatric Surgery, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Todd M
authors.initials: TM
authors.lastname: Jenkins
authors.affiliation: Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: David E
authors.initials: DE
authors.lastname: Kleiner
authors.affiliation: University of New Mexico Cancer Center, Biostatistics Shared Resource, Albuquerque, New Mexico.
authors.forename: Tawny W
authors.initials: TW
authors.lastname: Boyce
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Reena
authors.initials: R
authors.lastname: Mourya
authors.affiliation: Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Rebekah
authors.initials: R
authors.lastname: Karns
authors.affiliation: Division of Pediatric Surgery, Texas Children's Hospital, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas.
authors.forename: Mary L
authors.initials: ML
authors.lastname: Brandt
authors.affiliation: Division of Pediatric Surgery, Women & Children's Hospital of Buffalo, University of Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York.
authors.forename: Carroll M
authors.initials: CM
authors.lastname: Harmon
authors.affiliation: Division of Pediatric Surgery, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Helmrath
authors.affiliation: Department of Pediatric Surgery, The Ohio State University College of Medicine and Nationwide Children's Hospital, Columbus, Ohio.
authors.forename: Marc P
authors.initials: MP
authors.lastname: Michalsky
authors.affiliation: Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
authors.forename: Anita P
authors.initials: AP
authors.lastname: Courcoulas
authors.affiliation: Division of Behavioral Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Meg H
authors.initials: MH
authors.lastname: Zeller
authors.affiliation: Division of Pediatric Surgery, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Inge
mesh_terms: D000293:Adolescent; D017677:Age Distribution; D000367:Age Factors; D000410:Alanine Transaminase / Q000097:blood; D050110:Bariatric Surgery; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008103:Liver Cirrhosis / Q000453:epidemiology; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D015999:Multivariate Analysis; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D016017:Odds Ratio; D063766:Pediatric Obesity / Q000175:diagnosis / Q000453:epidemiology / Q000601:surgery*; D011237:Predictive Value of Tests; D015995:Prevalence; D011446:Prospective Studies; D012333:RNA, Messenger / Q000032:analysis; D012307:Risk Factors; D012720:Severity of Illness Index; D014481:United States / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D000410:Alanine Transaminase
keywords: Inflammation; Microarray; Pediatric; Severe Obesity