Paediatric gastroenterology evaluation of overweight and obese children referred from primary care for suspected non-alcoholic fatty liver disease

J B Schwimmer, K P Newton, H I Awai, L J Choi, M A Garcia, L L Ellis, K Vanderwall, J Fontanesi, J B Schwimmer, K P Newton, H I Awai, L J Choi, M A Garcia, L L Ellis, K Vanderwall, J Fontanesi

Abstract

Background: Screening overweight and obese children for non-alcoholic fatty liver disease (NAFLD) is recommended by paediatric and endocrinology societies. However, gastroenterology societies have called for more data before making a formal recommendation.

Aim: To determine whether the detection of suspected NAFLD in overweight and obese children through screening in primary care and referral to paediatric gastroenterology resulted in a correct diagnosis of NAFLD.

Methods: Information generated in the clinical evaluation of 347 children identified with suspected NAFLD through screening in primary care and referral to paediatric gastroenterology was captured prospectively. Diagnostic outcomes were reported. The diagnostic performance of two times the upper limit of normal (ULN) for alanine aminotransferase (ALT) was assessed.

Results: Non-alcoholic fatty liver disease was diagnosed in 55% of children identified by screening and referral. Liver disease other than NAFLD was present in 18% of those referred. Autoimmune hepatitis was the most common alternative diagnosis. Children with NAFLD had significantly (P < 0.05) higher screening ALT (98 ± 95) than children with liver disease other than NAFLD (86 ± 74). Advanced fibrosis was present in 11% of children. For the diagnosis of NAFLD, screening ALT two times the clinical ULN had a sensitivity of 57% and a specificity of 71%.

Conclusions: Screening of overweight and obese children in primary care for NAFLD with referral to paediatric gastroenterology has the potential to identify clinically relevant liver pathology. Consensus is needed on how to value the risk and rewards of screening and referral, to identify children with liver disease in the most appropriate manner.

© 2013 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Flow chart shows study the application of inclusion and exclusion criteria along with progression to final diagnosis. In the terminal nodes for diagnosis, the cumulative number is greater than the number biopsied because two children had dual diagnosis.
Figure 2
Figure 2
Box and whiskers plot for screening ALT separated by final diagnosis: no liver disease, NAFLD, or liver disease other than NAFLD. Within each diagnostic category, data are shown separately for boys (○) and girls (□).The horizontal lines inside the boxes represent the median, the box edges show the lower and upper quartiles and the whiskers show the minimum and maximum values. The Y axis was truncated at 450 U/L. Only the group of boys with NAFLD included outliers with screening ALT above 450 U/L.

References

    1. Schwimmer JB, Deutsch R, Kahen T, Lavine JE, Stanley C, Behling C. Prevalence of fatty liver in children and adolescents. Pediatrics. 2006;118:1388–93.
    1. Lindback SM, Gabbert C, Johnson BL, et al. Pediatric nonalcoholic fatty liver disease: a comprehensive review. Adv Pediatr. 2010;57:85–140.
    1. Pardee PE, Lavine JE, Schwimmer JB. Diagnosis and treatment of pediatric nonalcoholic steatohepatitis and the implications for bariatric surgery. Semin Pediatr Surg. 2009;18:144–51.
    1. Rubinstein E, Lavine JE, Schwimmer JB. Hepatic, cardiovascular, and endocrine outcomes of the histological subphenotypes of nonalcoholic fatty liver disease. Semin Liver Dis. 2008;28:380–5.
    1. Schwimmer JB, Behling C, Newbury R, et al. Histopathology of pediatric nonalcoholic fatty liver disease. Hepatology. 2005;42:641–9.
    1. Molleston JP, White F, Teckman J, Fitzgerald JF. Obese children with steatohepatitis can develop cirrhosis in childhood. Am J Gastroenterol. 2002;97:2460–2.
    1. Neuschwander-Tetri BA, Caldwell SH. Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference. Hepatology. 2003;37:1202–19.
    1. 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;24:772–6.
    1. Strauss RS, Barlow SE, Dietz WH. Prevalence of abnormal serum aminotransferase values in overweight and obese adolescents. J Pediatr. 2000;136:727–33.
    1. Rashid M, Roberts EA. Nonalcoholic steatohepatitis in children. J Pediatr Gastroenterol Nutr. 2000;30:48–53.
    1. Schwimmer JB, 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;143:500–5.
    1. Schwimmer JB, McGreal N, Deutsch R, Finegold MJ, Lavine JE. Influence of gender, race, and ethnicity on suspected fatty liver in obese adolescents. Pediatrics. 2005;115:e561–5.
    1. Welsh JA, Karpen S, Vos MB. Increasing prevalence of nonalcoholic fatty liver disease among United States adolescents, 1988-1994 to 2007-2010. J Pediatr. 2013;162:496–500 e1.
    1. Riley MR, Bass NM, Rosenthal P, Merriman RB. Underdiagnosis of pediatric obesity and underscreening for fatty liver disease and metabolic syndrome by pediatricians and pediatric subspecialists. J Pediatr. 2005;147:839–42.
    1. Barlow SE, Expert C. Expert committee recommendations regarding the prevention, assessment, and treatment of child and adolescent overweight and obesity: summary report. Pediatrics. 2007;120(Suppl. 4):S164–92.
    1. August GP, Caprio S, Fennoy I, et al. Prevention and treatment of pediatric obesity: an endocrine society clinical practice guideline based on expert opinion. J Clin Endocrinol Metabol. 2008;93:4576–99.
    1. Vajro P, Lenta S, Socha P, et al. Diagnosis of nonalcoholic fatty liver disease in children and adolescents: position paper of the ESPGHAN Hepatology Committee. J Pediatr Gastroenterol Nutr. 2012;54:700–13.
    1. Krebs NF, Himes JH, Jacobson D, Nicklas TA, Guilday P, Styne D. Assessment of child and adolescent overweight and obesity. Pediatrics. 2007;120(Suppl. 4):S193–228.
    1. Chalasani N, Younossi Z, Lavine JE, et al. 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. 2012;142:1592–609.
    1. Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology. 2012;55:2005–23.
    1. Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Am J Gastroenterol. 2012;107:811–26.
    1. D'Agata ID, Balistreri WF. Evaluation of liver disease in the pediatric patient. Pediatr Rev. 1999;20:376–90.
    1. Tsouka A, McLin VA. Complications of chronic liver disease. Clin Res Hepatol Gastroenterol. 2012;36:262–7.
    1. Suchy FJ, Sokol RJ, Balistreri WF. Liver Disease in Children. 3rd ed. New York: Cambridge University Press; 2007.
    1. Ovchinsky N, Moreira RK, Lefkowitch JH, Lavine JE. Liver biopsy in modern clinical practice: a pediatric point-of-view. Adv Anat Pathol. 2012;19:250–62.
    1. Kleiner DE, Brunt EM, Van Natta M, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41:1313–21.
    1. Poynard T, Bedossa P, Opolon P. Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups. Lancet. 1997;349:825–32.
    1. Kleinman R, Goulet O, Mieli-Vergani G, Sanderson I, Sherman P, Shneider B. Walker's Pediatric Gastrointestinal Disease. 5th ed. Shelton: People's Medical Publishing House; 2008.
    1. Burt AD, Portmann BC, Ferrell LD. MacSween's Pathology of the Liver. 6th ed. London: MacSween's Pathology of the Liver; 2011.
    1. Manns MP, Czaja AJ, Gorham JD, et al. Diagnosis and management of autoimmune hepatitis. Hepatology. 2010;51:2193–213.
    1. Schwimmer JB, Dunn W, Norman GJ, et al. SAFETY study: alanine aminotransferase cutoff values are set too high for reliable detection of pediatric chronic liver disease. Gastroenterology. 2010;138:1357–64.
    1. Dowman JK, Tomlinson JW, Newsome PN. Systematic review: the diagnosis and staging of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Aliment Pharmacol Ther. 2011;33:525–40.
    1. Bedogni G, Bellentani S, Miglioli L, et al. The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population. BMC Gastroenterol. 2006;6:33.
    1. Sterling RK, Lissen E, Clumeck N, et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006;43:1317–25.
    1. Shah AG, Lydecker A, Murray K, et al. Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2009;7:1104–12.
    1. Nobili V, Alisi A, Vania A, Tiribelli C, Pietrobattista A, Bedogni G. The pediatric NAFLD fibrosis index: a predictor of liver fibrosis in children with non-alcoholic fatty liver disease. BMC Med. 2009;7:21.
    1. Patton HM, Lavine JE, Van NattaML, et al. Clinical correlates of histopathology in pediatric nonalcoholic steatohepatitis. Gastroenterology. 2008;135:1961–71, e2.
    1. Kistler KD, Molleston J, Unalp A, Abrams SH, Behling C, Schwimmer JB. Symptoms and quality of life in obese children and adolescents with nonalcoholic fatty liver disease. Aliment Pharmacol Ther. 2009;31:396–406.
    1. Feldstein AE, Charatcharoenwitthaya P, Treeprasertsuk S, Benson JT, Enders FB, Angulo P. The natural history of non-alcoholic fatty liver disease in children: a follow-up study for up to 20 years. Gut. 2009;58:1538–44.
    1. Schwimmer JB, Pardee PE, Lavine JE, Blumkin AK, Cook S. Cardiovascular risk factors and the metabolic syndrome in pediatric nonalcoholic fatty liver disease. Circulation. 2008;118:277–83.
    1. Pardee PE, Dunn W, Schwimmer JB. Non-alcoholic fatty liver disease is associated with low bone mineral density in obese children. Aliment Pharmacol Ther. 2012;35:248–54.

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