A clinically relevant method to screen for hepatic steatosis in overweight adolescents: a cross sectional study

BMC Pediatrics

Jonathan McGavock¹  Lori Berard²  Lawrence Ryner²  Niranjan Venugopal²  Andrea MacIntosh²  Jacqueline Hay²  Kristy Wittmeier¹  Brandy Wicklow¹  Vera Saad² 

[1] Diabetes Research Envisioned and Accomplished in Manitoba Theme, 715 McDermot Avenue, Winnipeg R3E 3P4, Mb, Canada;The Diabetes Research Group, Department of Internal Medicine, Faculty of Medicine, University of Manitoba, 835 McDermot Avenue, Winnipeg R3E 0 T8, MB, Canada

关键词: Lipotoxicity;    Obesity;    Adolescents;    Magnetic resonance spectroscopy;    ALT;    Fatty liver;   

Others  :  1231036
DOI  :  10.1186/s12887-015-0465-x

 received in 2014-12-31, accepted in 2015-09-25,  发布年份 2015

【 摘 要 】

Background

To develop a screening algorithm to detect hepatic steatosis in overweight and obese adolescents.

Methods

We performed a cross sectional study of 129 overweight adolescents 13–18 yrs. The primary outcome, hepatic steatosis was defined as an intracellular triglyceride content > 5.5 mg/g and quantified using¹ H-magenetic resonance spectroscopy. Primary predictor variables included, alanine and aspartate transaminases (ALT/AST) and features of the metabolic syndrome.

Results

Hepatic steatosis was present in 33 % of overweight and obese adolescents. Adolescents with hepatic steatosis were more likely to be boys (adjusted OR: 4.8; 95 % CI: 2.5–10.5), display a higher waist circumference (111 ± 12 vs 100 ± 13 cm, p < 0.001) and have metabolic syndrome (adjusted OR: 5.1; 95 % CI: 1.6–16.4). Serum ALT predicted hepatic steatosis in boys (AUC: 0.82; 95 % CI: 0.70–0.95; p < 0.001) but not girls (AUC = 0.63; 95 % CI: 0.46–0.75, p = 0.16). An ALT >20 U/L, combined with the presence of metabolic syndrome, male gender and an elevated waist circumference provided the best model (AUC 0.85) with high sensitivity (72 %) and specificity (82 %) and positive and negative predictive values of 61 % and 89 % respectively.

Conclusions

Serum transaminases provide modest predictive value for hepatic steatosis in youth. The ALT threshold for predicting hepatic steatosis is significantly lower than current clinical thresholds for predicting non-alcoholic fatty liver disease. The addition of ALT, presence of the metabolic syndrome and male gender significant improve the ability to predict hepatic steatosis.

【 授权许可】

   
2015 Saad et al.

【 图 表 】

Fig. 1.

Fig. 2.

【 参考文献 】

• [1]Alisi A, Feldstein AE, Villani A, Raponi M, Nobili V. Pediatric nonalcoholic fatty liver disease: a multidisciplinary approach. Nat Rev Gastroenterol Hepatol. 2012; 9:152-61.
• [2]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.
• [3]Marion AW, Baker AJ, Dhawan A. Fatty liver disease in children. Arch Dis Child. 2004; 89:648-52.
• [4]Wittmeier KD, Wicklow BA, MacIntosh AC, Sellers EA, Ryner LN, Serrai H et al.. Hepatic steatosis and low cardiorespiratory fitness in youth with type 2 diabetes. Obesity (Silver Spring). 2012; 20:1034-40.
• [5]Koot BG, van der Baan-Slootweg OH, Bohte AE, Nederveen AJ, van Werven JR, Tamminga-Smeulders CL et al.. Accuracy of prediction scores and novel biomarkers for predicting nonalcoholic fatty liver disease in obese children. Obesity (Silver Spring). 2013; 21:583-90.
• [6]Barlow SE. 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.
• [7]Alisi A, Nobili V. Sensitive non-invasive circulating markers in paediatric non-alcoholic fatty liver disease. Pediatr Obes. 2012; 7:89-91.
• [8]Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K 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.
• [9]Schwimmer JB, Dunn W, Norman GJ, Pardee PE, Middleton MS, Kerkar N 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.
• [10]Wicklow BA, Wittmeier KD, MacIntosh AC, Sellers EA, Ryner L, Serrai H et al.. Metabolic consequences of hepatic steatosis in overweight and obese adolescents. Diabetes Care. 2012; 35:905-10.
• [11]Nobili V, Bedogni G, Berni Canani R, Brambilla P, Cianfarani S, Pietrobelli A et al.. The potential role of fatty liver in paediatric metabolic syndrome: a distinct phenotype with high metabolic risk? Pediatr Obes. 2012; 7:e75-80.
• [12]Fintini D, Pietrobattista A, Morino G, Cafiero G, Calzolari A, Turchetta A et al.. Energy expenditure and insulin sensitivity evaluation in obese children affected by hepatosteatosis. Pediatr Obes. 2012; 7:e14-7.
• [13]Cole TJ, Bellizzi MC, Flegal KM, Dietz WH. Establishing a standard definition for child overweight and obesity worldwide: international survey. BMJ. 2000; 320:1240-3.
• [14]Poustchi H, George J, Esmaili S, Esna-Ashari F, Ardalan G, Sepanlou SG et al.. Gender differences in healthy ranges for serum alanine aminotransferase levels in adolescence. PLoS One. 2011; 6:e21178.
• [15]Szczepaniak LS, Nurenberg P, Leonard D, Browning JD, Reingold JS, Grundy S et al.. Magnetic resonance spectroscopy to measure hepatic triglyceride content: prevalence of hepatic steatosis in the general population. Am J Physiol Endocrinol Metab. 2005; 288:E462-8.
• [16]Provencher SW. Automatic quantitation of localized in vivo 1H spectra with LCModel. NMR Biomed. 2001; 14:260-4.
• [17]Jolliffe CJ, Janssen I. Development of age-specific adolescent metabolic syndrome criteria that are linked to the Adult Treatment Panel III and International Diabetes Federation criteria. J Am Coll Cardiol. 2007; 49:891-8.
• [18]Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL et al.. Seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure. Hypertension. 2003; 42:1206-52.
• [19]Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC et al.. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985; 28:412-9.
• [20]CDC Growth Charts [http://www.cdc.gov.proxy2.lib.umanitoba.ca/growthcharts]. Accessed March 16th, 2014.
• [21]Nobili V, Alkhouri N, Alisi A, Della Corte C, Fitzpatrick E, Raponi M et al.. Nonalcoholic Fatty Liver Disease: A Challenge for Pediatricians. JAMA Pediatr. 2015; 169(2):170-6.
• [22]Alterio A, Alisi A, Liccardo D, Nobili V. Non-alcoholic Fatty liver and metabolic syndrome in children: a vicious circle. Horm Res Paediatr. 2014; 82:283-9.
• [23]Giorgio V, Prono F, Graziano F, Nobili V. Pediatric non alcoholic fatty liver disease: old and new concepts on development, progression, metabolic insight and potential treatment targets. BMC Pediatr. 2013; 13:40. BioMed Central Full Text
• [24]Alisi A, Cianfarani S, Manco M, Agostoni C, Nobili V. Non-alcoholic fatty liver disease and metabolic syndrome in adolescents: pathogenetic role of genetic background and intrauterine environment. Ann Med. 2012; 44:29-40.
• [25]Molleston JP, Schwimmer JB, Yates KP, Murray KF, Cummings OW, Lavine JE et al.. Histological abnormalities in children with nonalcoholic fatty liver disease and normal or mildly elevated alanine aminotransferase levels. J Pediatr. 2014; 164:707-713 e3.
• [26]Manco M, Nobili V. Utility of magnetic resonance imaging in the evaluation of hepatic fat content. Hepatology. 2009; 50:328-9.
• [27]Estep JM, Birerdinc A, Younossi Z. Non-invasive diagnostic tests for non-alcoholic fatty liver disease. Curr Mol Med. 2010; 10:166-72.
• [28]Nobili V, Della Corte C, Monti L, Alisi A, Feldstein A. The use of ultrasound in clinical setting for children affected by NAFLD: is it safe and accurate? Ital J Pediatr. 2011; 37:36. BioMed Central Full Text
• [29]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; 350:2362-74.
• [30]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.
• [31]Franks PW, Hanson RL, Knowler WC, Moffett C, Enos G, Infante AM et al.. Childhood predictors of young-onset type 2 diabetes. Diabetes. 2007; 56:2964-72.
• [32]Monteiro PA, Antunes Bde M, Silveira LS, Christofaro DG, Fernandes RA, Freitas Junior IF et al.. Body composition variables as predictors of NAFLD by ultrasound in obese children and adolescents. BMC Pediatr. 2014; 14:25. BioMed Central Full Text
• [33]Staiano AE, Katzmarzyk PT. Ethnic and sex differences in body fat and visceral and subcutaneous adiposity in children and adolescents. Int J Obes (Lond). 2012; 36:1261-9.
• [34]Fabbrini E, Magkos F, Mohammed BS, Pietka T, Abumrad NA, Patterson BW et al.. Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity. Proc Natl Acad Sci U S A. 2009; 106:15430-5.
• [35]Schwimmer JB, Deutsch R, Rauch JB, Behling C, Newbury R, Lavine JE et al.. Obesity, insulin resistance, and other clinicopathological correlates of pediatric nonalcoholic fatty liver disease. J Pediatr. 2003; 143:500-5.
• [36]Westerbacka J, Corner A, Tiikkainen M, Tamminen M, Vehkavaara S, Hakkinen AM et al.. Women and men have similar amounts of liver and intra-abdominal fat, despite more subcutaneous fat in women: implications for sex differences in markers of cardiovascular risk. Diabetologia. 2004; 47:1360-9.
• [37]Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, Cohen JC et al.. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology. 2004; 40:1387-95.