Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Pediatric Highlight
  • Published:

Obese boys at increased risk for nonalcoholic liver disease: evaluation of 16 390 overweight or obese children and adolescents

International Journal of Obesity volume 34, pages 1468–1474 (2010)Cite this article

Subjects

Abstract

Objective:

Comorbidities of childhood obesity challenge health-care systems in Europe. Further, there is a lack of population-specific prevalence data and diagnostic strategies available, especially for obesity-related disturbances of liver function. Therefore, the prevalence of elevated liver enzymes and their relationship to biological parameters were studied in a large pediatric obesity cohort.

Methods:

In 111 specialized pediatric obesity centers in Germany, Austria and Switzerland, 16 390 children and adolescents (age 12.4±2.6 years, 58% boys) were categorized as overweight (body mass index (BMI) >90th percentile) and obese (>97th percentile) and studied for related comorbidities, especially nonalcoholic fatty liver disease (NAFLD; as defined by aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >50 U l−1). Data were collected using a standardized software program (APV) for longitudinal multicenter documentation. Pseudonymized data were transmitted for central statistical analysis.

Results:

In this pediatric cohort, 16% of the study population was overweight, 46% obese and 35% extremely obese (>99.5th percentile extreme obesity (Xob)). NAFLD was present in 11% of the study population, but predominantly in boys (boys vs girls; 14.4:7.4%; P<0.001), in Xob (obese vs Xob; 9.5:17.0%; P<0.001) and in older age (< 12 vs ⩾12 years; 8:12%; P<0.001; adjusted for BMI). ALT >50 U l−1 was significantly associated with fasting insulin and BMI-SDS. In multiple logistic regression models, Xob and male gender were strongly associated with NAFLD (odds ratio Xob vs normal weight=3.2; boys vs girls OR=2.3).

Conclusion:

In a large cohort of overweight and obese European children and adolescents, markers of nonalcoholic liver disease, especially ALT, are frequent and predicted by Xob and male gender. The results underline the epidemiological dimension of this obesity-related morbidity even in childhood. Therefore, at least ALT is recommended as a screening parameter in basic care.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

References

  1. Wang Y, Lobstein T . Worldwide trends in childhood overweight and obesity. Int J Pediatr Obes 2006; 1: 11–25.

    Article  Google Scholar 

  2. Weiss R, Dziura J, Burgert TS, Tamborlane WV, Taksali SE, Yeckel CW et al. Obesity and the metabolic syndrome in children and adolescents. N Engl J Med 2004; 350: 2362–2374.

    Article  CAS  Google Scholar 

  3. Baranowski T, Cooper DM, Harrell J, Hirst K, Kaufman FR, Goran M et al. Presence of diabetes risk factors in a large U.S. eighth-grade cohort. Diabetes Care 2006; 29: 212–217.

    Article  CAS  Google Scholar 

  4. Wiegand S, Maikowski U, Blankenstein O, Biebermann H, Tarnow P, Gruters A . Type 2 diabetes and impaired glucose tolerance in European children and adolescents with obesity—a problem that is no longer restricted to minority groups. Eur J Endocrinol 2004; 151: 199–206.

    Article  CAS  Google Scholar 

  5. I’Allemand D, Wiegand S, Reinehr T, Müller J, Wabitsch M, Widhalm K et al. Cardiovascular risk in 26 008 European overweight children as established by a multicenter database. Obesity (Silver Spring) 2008; 16: 1672–1679.

    Article  Google Scholar 

  6. Moran JR, Ghishan FK, Halter SA, Greene HL . Steatohepatitis in obese children: a cause of chronic liver dysfunction. Am J Gastroenterol 1983; 78: 374–377.

    CAS  PubMed  Google Scholar 

  7. Patton HM, Sirlin C, Behling C, Middleton M, Schwimmer JB, Lavine JE . Pediatric nonalcoholic fatty liver disease: a critical appraisal of current data and implications for future research. J Pediatr Gastroenterol Nutr 2006; 43: 413–427.

    Article  Google Scholar 

  8. De Lèdinghen V, Le Bail B, Rebouissoux L, Fournier C, Foucher J et al. Liver stiffness measurement in children with fibroscan. Feasibility study and comparison with fibrotest, aspartate transaminase to platelets ratio index, and liver biopsy. J Pediatr Gastroenterol Nutr 2007; 45: 443–450.

    Article  Google Scholar 

  9. Patton HM, Lavine JE, Van Natta ML, Schwimmer JB, Kleiner D, Molleston J . Nonalcoholic Steatohepatitis Clinical Research Network. Clinical correlates of histopathology in pediatric nonalcoholic steatohepatitis. Gastroenterology 2008; 135: 1961–1971.

    Article  Google Scholar 

  10. Fraser A, Longnecker MP, Lawlor DA . Prevalence of elevated alanine aminotransferase among US adolescents and associated factors: NHANES 1999–2004. Gastroenterology 2007; 133: 1814–1820.

    Article  CAS  Google Scholar 

  11. van Vliet M, von Rosenstiel IA, Schindhelm RK, Brandjes DP, Beijnen JH, Diamant M . The association of elevated alanine aminotransferase and the metabolic syndrome in an overweight and obese pediatric population of multi-ethnic origin. Eur J Pediatr 2009; 168: 585–591.

    Article  CAS  Google Scholar 

  12. Wedemeyer H, Hofmann WP, Lueth S, Malinski P, Thimme R, Tacke F et al. ALT als Screeningparameter für Lebererkrankungen: eine kritische Evaluation der Evidenz. ALT screening for chronic liver diseases: scrutinizing the evidence. Z Gastroenterol 2010; 48: 46–55.

    Article  CAS  Google Scholar 

  13. Guidelines of the German Working Group of Childhood obesity. Available from www.a-g-a.de.

  14. Reinehr T, Wabitsch M, Andler W, Beyer P, Bottner A, Chen-Stute A et al. Medical care of obese children and adolescents. APV: a standardised multicentre documentation derived to study initial presentation and cardiovascular risk factors in patients transferred to specialised treatment institutions. Eur J Pediatr 2004; 163: 308–312.

    Article  Google Scholar 

  15. Kromeyer-Hauschild K, Wabitsch M, Kunze D . Perzentile für den Body-mass-Index für das Kindes- und Jugendalter unter Heranziehung verschiedener deutscher Stichproben. Monatsschr Kinderheilk 2001; 149: 807–818.

    Article  Google Scholar 

  16. Cole TJ, Bellizzi MC, Flegal KM, Dietz WH . Establishing a standard definition for child overweight and obesity worldwide: international survey. BMJ 2000; 320: 1240–1243.

    Article  CAS  Google Scholar 

  17. Cole TJ . The LMS method for constructing normalized growth standards. Eur J Clin Nutr 1990; 44: 45–60.

    CAS  Google Scholar 

  18. de Man SA, André JL, Bachmann H, Grobbee DE, Ibsen KK, Laaser U et al. Blood pressure in childhood: pooled findings of six European studies. J Hypertens 1991; 9: 109–114.

    Article  CAS  Google Scholar 

  19. Kavey REW, Daniels SR, Lauer RM, Atins DL, Hayman LL, Taubert K . American Heart Association Guidelines for primary prevention of atherosclerotic cardiovascular disease beginning in childhood. Circulation 2003; 107: 1562–1566.

    Article  Google Scholar 

  20. Alberti KG, Zimmet PZ . Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 1998; 15: 539–553.

    Article  CAS  Google Scholar 

  21. Dmitrienko EA . Analysis of Clinical Trials Using SAS. SAS Press: Cary, NC, 2005.

    Google Scholar 

  22. Kawasaki T, Hashimoto N, Kikuchi T, Takahashi H, Uchiyama M . The relationship between fatty liver and hyperinsulinemia in obese Japanese children. J Pediatr Gastroenterol Nutr 1997; 24: 317–321.

    Article  CAS  Google Scholar 

  23. Manton ND, Lipsett J, Moore DJ, Davidson GP, Bourne AJ, Couper RT . Non-alcoholic steatohepatitis in children and adolescents. Med J Aust 2000; 173: 476–479.

    CAS  PubMed  Google Scholar 

  24. Franzese A, Vajro P, Argenziano A, Puzziello A, Iannucci MP, Saviano MC et al. Liver involvement in obese children. Ultrasonography and liver enzyme levels at diagnosis and during follow-up in an Italian population. Dig Dis Sci 1997; 42: 1428–1432.

    Article  CAS  Google Scholar 

  25. Nobili V, Reale A, Alisi A, Morino G, Trenta I, Pisani M et al. Elevated serum ALT in children presenting to the emergency unit: relationship with NAFLD. Dig Liver Dis 2009; 41: 749–752.

    Article  CAS  Google Scholar 

  26. Schwimmer JB, Deutsch R, Kahen T, Lavine JE, Stanley C, Behling C . Prevalence of fatty liver in children and adolescents. Pediatrics 2006; 118: 1388–1393.

    Article  Google Scholar 

  27. Di Bonito P, Sanguigno E, Di Fraia T, Forziato C, Boccia G, Saitta F et al. Association of elevated serum alanine aminotransferase with metabolic factors in obese children: sex-related analysis. Metabolism 2009; 58: 368–372.

    Article  CAS  Google Scholar 

  28. Kim HC, Nam CM, Jee SH, Han KH, Oh DK, Suh I . Normal serum aminotransferase concentration and risk of mortality from liver diseases: prospective cohort study. BMJ 2004; 328: 983.

    Article  CAS  Google Scholar 

  29. A-Kader HH, Henderson J, Vanhoesen K, Ghishan F, Bhattacharyya A . Nonalcoholic fatty liver disease in children: a single center experience. Clin Gastroenterol Hepatol 2008; 6: 799–802.

    Article  Google Scholar 

  30. Roberts EA . Pediatric nonalcoholic fatty liver disease (NAFLD): a ‘growing’ problem? J Hepatol 2007; 46: 1133–1142.

    Article  CAS  Google Scholar 

  31. Schwimmer JB, Khorram O, Chiu V, Schwimmer WB . Abnormal aminotransferase activity in women with polycystic ovary syndrome. Fertil Steril 2005; 83: 494–497.

    Article  CAS  Google Scholar 

  32. Brzozowska MM, Ostapowicz G, Weltman MD . An association between non-alcoholic fatty liver disease and polycystic ovarian syndrome. J Gastroenterol Hepatol 2009; 24: 243–247.

    Article  CAS  Google Scholar 

  33. Clark JM, Brancati FL, Diehl AM . Nonalcoholic fatty liver disease. Gastroenterology 2002; 122: 1649–1657.

    Article  Google Scholar 

  34. Anezaki Y, Ohshima S, Ishii H, Kinoshita N, Dohmen T, Kataoka E et al. Sex difference in the liver of hepatocyte-specific Pten-deficient mice: a model of nonalcoholic steatohepatitis. Hepatol Res 2009; 39: 609–618.

    Article  CAS  Google Scholar 

  35. Reinehr T, Toschke AM . Onset of puberty and cardiovascular risk factors in untreated obese children and adolescents: a 1-year follow-up study. Arch Pediatr Adolesc Med 2009; 163: 709–715.

    Article  Google Scholar 

  36. Reinehr T, Schmidt C, Toschke AM, Andler W . Lifestyle intervention in obese children with non-alcoholic fatty liver disease: 2-year follow-up study. Arch Dis Child 2009; 94: 437–442.

    Article  CAS  Google Scholar 

  37. McCullough AJ . Pathophysiology of nonalcoholic steatohepatitis. J Clin Gastroenterol 2006; 40: S17–S29.

    CAS  PubMed  Google Scholar 

  38. Farrell GC, Larter CZ . Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology 2006; 43: S99–S112.

    Article  CAS  Google Scholar 

  39. Manco M, Marcellini M, Devito R, Comparcola D, Sartorelli MR, Nobili V . Metabolic syndrome and liver histology in paediatric non-alcoholic steatohepatitis. Int J Obes (Lond) 2008; 32: 381–387.

    Article  CAS  Google Scholar 

  40. Burgert TS, Taksali SE, Dziura J, Goodman TR, Yeckel CW, Papademetris X et al. Alanine aminotransferase levels and fatty liver in childhood obesity: associations with insulin resistance, adiponectin, and visceral fat. J Clin Endocrinol Metab 2006; 91: 4287–4294.

    Article  CAS  Google Scholar 

  41. Denzer C, Thiere D, Muche R, Koenig W, Mayer H, Kratzer W et al. Gender-specific prevalences of fatty liver in obese children and adolescents: roles of body fat distribution, sex steroids, and insulin resistance. J Clin Endocrinol Metab 2009; 94: 3872–3881.

    Article  CAS  Google Scholar 

  42. Kleiser C, Schaffrath Rosario A, Mensink GB, Prinz-Langenohl R, Kurth BM . Potential determinants of obesity among children and adolescents in Germany: results from the cross-sectional KiGGS Study. BMC Public Health 2009; 2: 9–46.

    Google Scholar 

Download references

Acknowledgements

The APV program was supported by the German Federal Ministry of Health and by the German ‘Competence Network Adipositas,’ which is initiated by the German Federal Ministry of Education and Research (Grant Number 01 GI0839). We thank all patients, obesity centers, investigators, and staff who participated in the APV initiative. A full listing of the participating centers has recently been published elsewhere.5 SW, TR and RH received grant support from of the German ‘Competence Network Adipositas,’ which is supported by the German Federal Ministry of Education and Research (Grant Number 01 GI0839).

Author information

Authors and Affiliations

  1. Department of Pediatric Endocrinology and Diabetology, Charité Children's Hospital, Universitätsmedizin Berlin, Germany

    S Wiegand

  2. Department of Pediatrics, German Clinic for Diagnostics, Wiesbaden, Germany

    K-M Keller

  3. Social Pediatric Center, University of Göttingen, Göttingen, Germany

    M Röbl

  4. Children's Hospital of Eastern Switzerland, St Gall, Switzerland

    D l'Allemand

  5. Department of Pediatric Nutrition Medicine, Vestische Children's Hospital University of Witten/Herdecke, Datteln, Germany

    T Reinehr

  6. Division of Clinical Nutrition, Department of Pediatrics, Obesity and Lipid Disorders, Medical University of Vienna, Vienna, Austria

    K Widhalm

  7. Department of Epidemiology, University of Ulm, Ulm, Germany

    R W Holl

Authors
  1. S Wiegand
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K-M Keller
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M Röbl
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D l'Allemand
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. T Reinehr
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. K Widhalm
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. R W Holl
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

on behalf of the APV-Study Group and the German Competence Network Adipositas

Corresponding author

Correspondence to S Wiegand.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wiegand, S., Keller, KM., Röbl, M. et al. Obese boys at increased risk for nonalcoholic liver disease: evaluation of 16 390 overweight or obese children and adolescents. Int J Obes 34, 1468–1474 (2010). https://doi.org/10.1038/ijo.2010.106

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ijo.2010.106

Keywords

This article is cited by

Search

Advanced search

Quick links