Abstract
Objective:
Our aim was to estimate prevalence of metabolic syndrome (MS), obesity and comorbidities in a cohort of 120 children (3–18 years) with biopsy-proven non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) and to evaluate correlations between clinical or biochemical variables and liver histology.
Research methods and procedures:
MS was diagnosed according to the adapted National Cholesterol Education Program criteria. Homeostatic model assessment of insulin resistance (HOMA-IR), quantitative insulin-sensitivity check index (QUICKI); and ISI composite, insulin secretion (insulin response at 30 min after a glucose load; HOMA-β cell; insulinogenic index) were all estimated. BMI z-score and total body fat (dual-energy X-ray absorptiometry) were evaluated as indexes of obesity.
Results:
MS was diagnosed in 66% of children. About 92% had weight above the 85th percentile, of which 42% were obese with weight above 97th percentile. Prevalence of hypertriglyceridaemia was 63%, low HDL cholesterol 45%, hypertension 40% and impaired glucose tolerance 10%. Levels of aminotransferases were higher as the number of comorbidities increased, the highest values being found in subjects with MS (P⩽0.05). Prevalence of a grade of steatosis ⩾2 (P=0.05) and fibrosis (P⩽0.01) was higher in subjects with MS. Histology was associated significantly with higher values of a number of clinical and biochemical parameters (steatosis ⩾2 with BMI z-score (P=0.04), fasting insulin (P=0.02), HOMA-IR (P=0.03), β-cell secretion (P=0.04); necroinflammation with BMI z-score (P=0.007), glucose (P⩽0.0001), cholesterol (P⩽0.04) and white blood cells (P=0.025); fibrosis with body weight (P=0.05), BMI z-score (P=0.03), cholesterol (P=0.05), triglycerides (P=0.05), fasting insulin (P⩽0.0001) and mean values of the hormone at the OGTT (P=0.03), HOMA-IR (P⩽0.0001)).
Conclusion:
Presence of MS or clinical and biochemical variables associated with the syndrome seems to be strictly related to histological features of NASH in paediatric fatty liver disease. Thus, routinely liver biopsy should be encouraged in these children.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Executive summary of the third report of The National Cholesterol Education Program (NCEP) Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA 2001; 285: 2486–2497.
Angulo P . Non-alcoholic fatty liver disease. N Engl J Med 2002; 346: 1221–1231.
Marchesini G, Brizi M, Bianchi G, Tomassetti S, Bugianesi E, Lenzi M et al. Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes 2001; 50: 1844–1850.
Oh SY, Cho YK, Kang MS, Yoo TW, Park JH, Kim HJ et al. The association between increased alanine aminotransferase activity and metabolic factors in nonalcoholic fatty liver disease. Metabolism 2006; 55: 1604–1609.
Hanley AJ, Williams K, Festa A, Wagenknecht LE, D’Agostino Jr RB, Haffner SM . Liver markers and development of the metabolic syndrome: the insulin resistance atherosclerosis study. Diabetes 2005; 54: 3140–3147.
Bedogni G, Miglioli L, Masutti F, Tiribelli C, Marchesini G, Bellentani S . Prevalence of and risk factors for nonalcoholic fatty liver disease: the Dionysos nutrition and liver study. Hepatology 2005; 42: 44–52.
Kang H, Greenson JK, Omo JT, Chao C, Peterman D, Anderson L et al. Metabolic syndrome is associated with greater histologic severity, higher carbohydrate, and lower fat diet in patients with NAFLD. Am J Gastroenterol 2006; 101: 2247–2253.
Haukeland JW, Konopski Z, Linnestad P, Azimy S, Marit Loberg E, Haaland T et al. Abnormal glucose tolerance is a predictor of steatohepatitis and fibrosis in patients with non-alcoholic fatty liver disease. Scand J Gastroenterol 2005; 40: 1469–1477.
Marchesini G, Bugianesi E, Forlani G, Cerrelli F, Lenzi M, Manini R et al. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology 2003; 37: 917–923.
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 2004; 40: 475–483.
Guzzaloni G, Grugni G, Minocci A, Moro D, Morabito F . Liver steatosis in juvenile obesity: correlations with lipid profile, hepatic biochemical parameters and glycemic and insulinemic responses to an oral glucose tolerance test. Int J Obes Relat Metab Disord 2000; 24: 772–776.
Nobili V, Marcellini M, Devito R, Ciampalini P, Piemonte F, Comparcola D et al. Nonalcoholic fatty liver disease in children: a prospective clinical–pathological study and effect of lifestyle advice. Hepatology 2006; 44: 458–465.
Schwimmer JR, Deutsch R, Rauch JB, Behling C, Newbury R, Lavine JE . Obesity, insulin resistance, and other clinicopathological correlates of pediatric nonalcoholic fatty liver disease. J Pediatr 2003; 143: 500–505.
Himes JH . Anthropometric Assessment of Nutritional Status. Wiley-Liss Inc.: New York, 1991.
Cole TJ, Bellizzi MC, Flegal KM, Dietz WH . Establishing a standard definition for child overweight obesity worldwide: International survey. BMJ 2000; 320: 1–6.
Boney CM, Verma A, Tucker R, Vohr BR . Metabolic syndrome in childhood: association with birth weight, maternal obesity, and gestational diabetes mellitus. Pediatrics 2005; 115: e290–e296.
American Academy of Pediatrics, National Cholesterol Education Program: report of the expert panel on blood cholesterol levels in children and adolescents. Pediatrics 1992; 89: 525–584.
Report of the second task force on blood pressure control in children—1987. Task Force on Blood Pressure Control in Children. National Heart, Lung, and Blood Institute, Bethesda, Maryland. Pediatrics 1987; 79: 1–25.
Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 1997; 20: 1183–1197.
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC . Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412–419.
Katz A, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G et al. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab 2000; 85: 2402–2410.
Matsuda M, De Fronzo RA . Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 1999; 22: 1462–1470.
Sluiter WJ, Erkelens DW, Reitsma WD, Doorenbos H . Glucose tolerance and insulin release, a mathematical approach I. Assay of the beta-cell response after oral glucose loading. Diabetes 1976; 25: 241–244.
Phillips DI, Clark PM, Hales CN, Osmond C . Understanding oral glucose tolerance: comparison of glucose or insulin measurements during the oral glucose tolerance test with specific measurements of insulin resistance and insulin secretion. Diabet Med 1994; 11: 286–292.
Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005; 41: 1313–1321.
Searle J, Kerr JRF, Halliday JW . Iron storage disease. In: MacSwwen RNM, Anthony PP, Scheuer PJ (eds). Pathology of the Liver, 2nd edn. Churchill Livingstone: Edinburgh, 1987.
Schwimmer JB, Behling C, Newbury R, Deutsch R, Nievergelt C, Schork NJ et al. Histopathology of pediatric nonalcoholic fatty liver disease. Hepatology 2005; 42: 641–649.
Conwell LS, Trost SG, Brown WJ, Batch JA . Indexes of insulin resistance and secretion in obese children and adolescents: a validation study. Diabetes Care 2004; 27: 314–319.
Cook S, Weitzman M, Auinger P, Nguyen M, Dietz WH . Prevalence of the metabolic syndrome phenotype in adolescents: findings from the Third National Health and Nutrition Examination Survey, 1988–1994. Arch Pediatr Adolesc Med 2003; 157: 821–827.
Kahn SE, Prigeon RL, McCulloch DK, Boyko EJ, Bergman RN, Schwartz MW et al. Quantification of the relationship between insulin sensitivity and beta-cell function in human subjects. Evidence for a hyperbolic function. Diabetes 1993; 42: 1663–1672.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Manco, M., Marcellini, M., DeVito, R. et al. Metabolic syndrome and liver histology in paediatric non-alcoholic steatohepatitis. Int J Obes 32, 381–387 (2008). https://doi.org/10.1038/sj.ijo.0803711
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.ijo.0803711
Keywords
This article is cited by
-
Dietitian-led lifestyle modification programme for obese Chinese adolescents with non-alcoholic fatty liver disease: a randomized controlled study
International Journal of Obesity (2018)
-
Waist-to-height ratio is a useful index for nonalcoholic fatty liver disease in children and adolescents: a secondary data analysis
BMC Public Health (2017)
-
Intensive lifestyle treatment for non-alcoholic fatty liver disease in children with severe obesity: inpatient versus ambulatory treatment
International Journal of Obesity (2016)