CoChat
Sign Up
Cited by 151Liver Disease Diagnosis and TreatmentBariatric Surgery and OutcomesOrgan Transplantation Techniques and Outcomes

High Prevalence of Nonalcoholic Fatty Liver Disease in Adolescents Undergoing Bariatric Surgery

Open access
Xanthakos, Stavra A., Jenkins, Todd M., Kleiner, David E., Boyce, Tawny W., Mourya, Reena, Karns, Rebekah, Brandt, Mary L., Harmon, Carroll M. +5 more·2015·Gastroenterology
DOI 10.1053/j.gastro.2015.05.039PMC PMC4654456
Open this paper in CoChat — free accountOpen PDF

Abstract

Background & aims 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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1053/j.gastro.2015.05.039

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • PNPLA3, CPEB4, and ASPG are linked to hepatic steatosis, steatohepatitis, and/or fibrosis.

    “PNPLA3, CPEB4, and ASPG, which are linked to hepatic steatosis, steatohepatitis, and/or fibrosis33,39–41”

    From Spatial transcriptomics of healthy and fibrotic human liver at single-cell resolution (2025) · cites this paper as [41]

    The Results (Hepatic Gene Expression Profiles; page unavailable) report gene-expression differences across NAFLD and NASH groups but do not identify PNPLA3, CPEB4, or ASPG. Searches for those three gene names found no passage in our copy linking them to steatosis, steatohepatitis, or fibrosis. (LLM, conf=0.72)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

No references could be resolved yet.

Research works printed but not linked: 40

  1. [1]Patton HM Lavine JE Van Natta ML Schwimmer JB Kleiner D Molleston J Clinical correlates of histopathology in pediatric nonalcoholic steatohepatitis Gastroenterology 12 2008 135 6 1961 1971 e1962 19013463 PMC2628583
  2. [2]Patton HM Yates K Unalp-Arida A Association between metabolic syndrome and liver histology among children with nonalcoholic Fatty liver disease Am J Gastroenterol 9 2010 105 9 2093 2102 20372110 PMC3070291
  3. [3]Lavine JE Schwimmer JB Van Natta ML Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial JAMA 27 4 2011 305 16 1659 1668 21521847 PMC3110082
  4. [4]Schwimmer JB Zepeda A Newton KP Longitudinal assessment of high blood pressure in children with nonalcoholic fatty liver disease PLoS One 2014 9 11 e112569 25419656 PMC4242611
  5. [5]Carter-Kent C Yerian LM Brunt EM Nonalcoholic steatohepatitis in children: a multicenter clinicopathological study Hepatology 10 2009 50 4 1113 1120 19637190 PMC2775705
  6. [7]Chalasani N Younossi Z Lavine JE The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology Gastroenterology 6 2012 142 7 1592 1609 22656328
  7. [8]Michalsky M Reichard K Inge T Pratt J Lenders C ASMBS pediatric committee best practice guidelines Surg Obes Relat Dis Jan-Feb 2012 8 1 1 7 22030146
  8. [9]Pratt JS Lenders CM Dionne EA Best practice updates for pediatric/adolescent weight loss surgery Obesity (Silver Spring) 5 2009 17 5 901 910 19396070 PMC3235623
  9. [10]Nobili V Vajro P Dezsofi A Indications and Limitations of Bariatric Intervention in Severely Obese Children and Adolescents With and Without Non-alcoholic Steatohepatitis: the ESPGHAN Hepatology Committee Position Statement J Pediatr Gastroenterol Nutr 2 2 2015 25591123
  10. [11]Xanthakos S Miles L Bucuvalas J Daniels S Garcia V Inge T Histologic spectrum of nonalcoholic fatty liver disease in morbidly obese adolescents Clin Gastroenterol Hepatol 2 2006 4 2 226 232 16469684
  11. [12]Inge TH Zeller MH Jenkins TM Perioperative outcomes of adolescents undergoing bariatric surgery: the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) study JAMA Pediatr 1 2014 168 1 47 53 24189578 PMC4060250
  12. [13]Kleiner DE Brunt EM Van Natta M Design and validation of a histological scoring system for nonalcoholic fatty liver disease Hepatology 6 2005 41 6 1313 1321 15915461
  13. [14]Brunt EM Kleiner DE Wilson LA Belt P Neuschwander-Tetri BA Nonalcoholic fatty liver disease (NAFLD) activity score and the histopathologic diagnosis in NAFLD: distinct clinicopathologic meanings Hepatology 3 2011 53 3 810 820 21319198 PMC3079483
  14. [15]Zou G A modified poisson regression approach to prospective studies with binary data American journal of epidemiology 1 4 2004 159 7 702 706 15033648
  15. [16]Spiegelman D Hertzmark E Easy SAS calculations for risk or prevalence ratios and differences American journal of epidemiology 1 8 2005 162 3 199 200 15987728
  16. [17]Schwimmer JB Dunn W Norman GJ SAFETY study: alanine aminotransferase cutoff values are set too high for reliable detection of pediatric chronic liver disease Gastroenterology 4 2010 138 4 1357 1364 1364 e1351-1352 20064512 PMC2846968
  17. [18]Chen J Bardes EE Aronow BJ Jegga AG ToppGene Suite for gene list enrichment analysis and candidate gene prioritization Nucleic Acids Res 7 2009 37 W305 311 Web Server issue 19465376 PMC2703978
  18. [19]Rockey DC Caldwell SH Goodman ZD Nelson RC Smith AD Liver biopsy Hepatology 3 2009 49 3 1017 1044 19243014
  19. [20]Loomba R Abraham M Unalp A Association between diabetes, family history of diabetes, and risk of nonalcoholic steatohepatitis and fibrosis Hepatology 9 2012 56 3 943 951 22505194 PMC3407289
  20. [21]Lee YJ Lee HR Shim JY Moon BS Lee JH Kim JK Relationship between white blood cell count and nonalcoholic fatty liver disease Digestive and liver disease: official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 12 2010 42 12 888 894 20472517
  21. [22]Angulo P Keach JC Batts KP Lindor KD Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis Hepatology 1999 30 6 1356 1362 10573511
  22. [23]Schwimmer JB Behling C Newbury R Histopathology of pediatric nonalcoholic fatty liver disease Hepatology 22 8 2005 42 3 641 649 16116629
  23. [24]Moylan CA Pang H Dellinger A Hepatic gene expression profiles differentiate presymptomatic patients with mild versus severe nonalcoholic fatty liver disease Hepatology 2 2014 59 2 471 482 23913408 PMC3982589
  24. [25]Schwimmer JB Deutsch R Kahen T Lavine JE Stanley C Behling C Prevalence of fatty liver in children and adolescents Pediatrics 10 2006 118 4 1388 1393 17015527
  25. [26]Abrams GA Kunde SS Lazenby AJ Clements RH Portal fibrosis and hepatic steatosis in morbidly obese subjects: A spectrum of nonalcoholic fatty liver disease Hepatology 8 2004 40 2 475 483 15368453
  26. [27]Gholam PM Flancbaum L Machan JT Charney DA Kotler DP Nonalcoholic fatty liver disease in severely obese subjects Am J Gastroenterol 2 2007 102 2 399 408 17311652
  27. [28]Kleiner DE Berk PD Hsu JY Hepatic pathology among patients without known liver disease undergoing bariatric surgery: observations and a perspective from the longitudinal assessment of bariatric surgery (LABS) study Semin Liver Dis 2 2014 34 1 98 107 24782263 PMC4139971
  28. [29]Porter SA Massaro JM Hoffmann U Vasan RS O'Donnel CJ Fox CS Abdominal subcutaneous adipose tissue: a protective fat depot Diabetes Care 6 2009 32 6 1068 1075 19244087 PMC2681034
  29. [30]Tran TT Yamamoto Y Gesta S Kahn CR Beneficial effects of subcutaneous fat transplantation on metabolism Cell metabolism 5 2008 7 5 410 420 18460332 PMC3204870
  30. [31]Zhu L Baker SS Liu W Lipid in the livers of adolescents with nonalcoholic steatohepatitis: combined effects of pathways on steatosis Metabolism 7 2011 60 7 1001 1011 21075404
  31. [32]Zhang Y Baker SS Baker RD Zhu R Zhu L Systematic analysis of the gene expression in the livers of nonalcoholic steatohepatitis: implications on potential biomarkers and molecular pathological mechanism PLoS One 2012 7 12 e51131 23300535 PMC3530598
  32. [33]Sreekumar R Rosado B Rasmussen D Charlton M Hepatic gene expression in histologically progressive nonalcoholic steatohepatitis Hepatology 7 2003 38 1 244 251 12830008
  33. [34]Younossi ZM Baranova A Ziegler K A genomic and proteomic study of the spectrum of nonalcoholic fatty liver disease Hepatology 9 2005 42 3 665 674 16116632
  34. [35]Bertola A Bonnafous S Anty R Hepatic expression patterns of inflammatory and immune response genes associated with obesity and NASH in morbidly obese patients PLoS One 2010 5 10 e13577 21042596 PMC2962651
  35. [36]Neuschwander-Tetri BA Loomba R Sanyal AJ Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial Lancet 7 11 2014 PMC4447192 25468160
  36. [37]Myronovych A Kirby M Ryan KK Vertical sleeve gastrectomy reduces hepatic steatosis while increasing serum bile acids in a weight-loss-independent manner Obesity (Silver Spring) 2 2014 22 2 390 400 23804416 PMC3836901
  37. [38]Kohli R Bradley D Setchell KD Eagon JC Abumrad N Klein S Weight loss induced by Roux-en-Y gastric bypass but not laparoscopic adjustable gastric banding increases circulating bile acids J Clin Endocrinol Metab 4 2013 98 4 E708 712 23457410 PMC3615197
  38. [39]Ryan KK Tremaroli V Clemmensen C FXR is a molecular target for the effects of vertical sleeve gastrectomy Nature 8 5 2014 509 7499 183 188 24670636 PMC4016120
  39. [40]Nalbantoglu IL Brunt EM Role of liver biopsy in nonalcoholic fatty liver disease World J Gastroenterol 21 7 2014 20 27 9026 9037 25083076 PMC4112884
  40. [41]Larson SP Bowers SP Palekar NA Ward JA Pulcini JP Harrison SA Histopathologic variability between the right and left lobes of the liver in morbidly obese patients undergoing Roux-en-Y bypass Clin Gastroenterol Hepatol 11 2007 5 11 1329 1332 17702661

Cited by

Sorted by citations

Authors
Xanthakos, S. A., Jenkins, T. M., Kleiner, D. E., Boyce, T. W., Mourya, R., Karns, R., Brandt, M. L., Harmon, C. M., Helmrath, M. A., Michalsky, M. P., Courcoulas, A. P., Zeller, M. H., & Inge, T. H.
Affiliations
  • Cincinnati Children's Hospital Medical Center (US)
  • National Institutes of Health (US)
  • UNM Comprehensive Cancer Center (US)
  • Baylor College of Medicine (US)
  • Women & Children's Hospital of Buffalo (US)
  • Nationwide Children's Hospital (US)
  • University of Pittsburgh Medical Center (US)
Corresponding author
Xanthakos, Stavra A.
ORCID
Venue
Gastroenterology
Publisher
Elsevier BV
Published
2015-09
Volume
149
Issue
3
Pages
623-634.e8
ISSN
0016-5085 (ISSN-L)
DOI
10.1053/j.gastro.2015.05.039
PMC
PMC4654456
OpenAlex
W1700352558
Cited by
151
References
0
Citations by year
2026: 9 · 2025: 11 · 2024: 22 · 2023: 14 · 2022: 10 · 2021: 18 · 2020: 11 · 2019: 15 · 2018: 13 · 2017: 14 · 2016: 10 · 2015: 3
FWCI
10.46
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Gastroenterology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Cincinnati Children's Hospital Medical Center (P30DK078392)
  • University of Cincinnati (P30 DK078392)
  • National Institutes of Health (UL1TR001425, UL1TR000005, DK100429, DK078392)
  • National Cancer Institute
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK 078392, UM1DK095710, U01DK066557, DK066557, U01DK072493/UM1 DK072493, R01DK100429, UM1DK072493, K23DK080888, U01DK072493, P30DK078392)
  • National Center for Advancing Translational Sciences
Topics
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Health Sciences › Medicine › Surgery › Bariatric Surgery and Outcomes
  • Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
Keywords
non-alcoholic fatty liver disease, adolescents, bariatric surgery, nonalcoholic steatohepatitis, liver fibrosis, obesity, prevalence, cardiometabolic risk factors, hypertension, diabetes mellitus, dyslipidemia, alanine aminotransferase, hepatic gene expression, macrophage chemotaxis, cholesterol absorption, fatty acid binding, liver biopsy histology
MeSH terms
Adolescent, Age Factors, Alanine Transaminase, Biopsy, Female, Gene Expression Regulation, Humans, Liver, Liver Cirrhosis, Longitudinal Studies, Male, Predictive Value of Tests, Prospective Studies, Risk Factors, RNA, Messenger, Severity of Illness Index, United States, Biomarkers, Prevalence, Multivariate Analysis, Logistic Models, Odds Ratio, Age Distribution, Gene Expression Profiling, Bariatric Surgery, Pediatric Obesity, Non-alcoholic Fatty Liver Disease

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review