NAFLD; Non alcoholic fatty liver disease is accumulation of excessive fat in liver. It progress to inflammation and cirrhosis. Ethnic differences and clinical heterogeneity regarding NAFLD is well known. More children are getting diagnosed. Multiple factors are involved in pathology of NAFLD. This review focuses on diagnosis of NAFLD children based on available guidelines and literature. Clinical approach to NAFLD is suggested.
Alfani, R.; Vassallo, E.; De Anseris, A.G.; Nazzaro, L.; D'Acunzo, I.; Porfito, C.; Mandato, C.; Vajro, P. Pediatric Fatty Liver and Obesity: Not Always Just a Matter of Non-Alcoholic Fatty Liver Disease. Children 2018, 5, 169.
Anna Di Sessa, Pierluigi Marzuillo, Stefano Guarino, Grazia Cirillo & Emanuele Miraglia del Giudice (2019): When a secondary form of pediatric nonalcoholic fattyliver disease should be suspected? Expert Review of Gastroenterology & Hepatology, DOI: 10.1080/17474124.2019.1605290
Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67(1):328-357
Vos MB, Abrams SH, Barlow SE, et al. NASPGHAN Clinical Practice Guideline for the Diagnosis and Treatment of Nonalcoholic Fatty Liver Disease in Children: Recommendations from the Expert Committee on NAFLD (ECON) and the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN). J Pediatr Gastroenterol Nutr. 2017;64(2):319-334. doi: 10.1097/MPG.00000 00000001482
Vajro P, Lenta S, Socha P, Dhawan A, McKiernan P, Baumann Uet al (2012) Diagnosis of nonalcoholic fatty liver disease in children and adolescents: position paper of the ESPGHAN hepatology committee. J Pediatr Gastroenterol Nutr 54:700-713
Eng K, Lopez R, Liccardo D, Nobili V, Alkhouri N (2014) A noninvasive prediction model for non-alcoholic steatohepatitis in paediatricpatients with non-alcoholic fatty liver disease. Dig Liver Dis 46:1008-1013
Bacopoulou F, Efthymiou V, Landis G, Rentoumis A, Chrousos GP (2015) Waist circumference, waist-to-hip ratio and waist-toheightratio reference percentiles for abdominal obesity among Greek adolescents. BMC Pediatr 4:15-50
Nobili V, Cutrera R, Liccardo D, Pavone M, Devito R, Giorgio V, et al. Obstructive sleep apnea syndrome affects liver histology and inflammatorycell activation in pediatric nonalcoholic fatty liver disease, regardless ofobesity/insulin resistance. Am J Respir Crit Care Med 2014 Jan 1;189(1): 66e76. https://doi.org/10.1164/rccm.201307-1339OC
Patton HM, Lavine JE, Van Natta ML, Schwimmer JB, Kleiner D, Molleston J (2008) Nonalcoholic steatohepatitis clinical research network. Clinical correlates of histopathology in pediatric non alcoholic steatohepatitis. Gastroenterology 135:1961-1971
Zhao K, Ju H, Wang H. Metabolic characteristics of obese children with fatty liver: A STROBE-compliant article. Medicine (Baltimore). 2019;98(16):e1 4939. doi: 10.1097/MD.00000000000 14939
Kim JY, Cho J, Yang HR. Biochemical Predictors of Early Onset Non-Alcoholic Fatty Liver Disease in Young Children with Obesity. J Korean Med Sci. 2018;33 (16):e122. Published 2018 Apr 16. doi: 10.3346/jkms.2018.33.e122
Molleston JP, Schwimmer JB, Yates KP, Murray KF, Cummings OW, Lavine JE et al (2014) NASH clinical research network. Histological abnormalities in children with nonalcoholic fatty liverdisease and normal or mildly elevated alanine aminotransferase levels. J Pediatr 164:707-713
Prokopowicz Z, Malecka-Tendera E, Matusik P. Predictive Value of Adiposity Level, Metabolic Syndrome, and Insulin Resistance for the Risk of Nonalcoholic Fatty Liver Disease Diagnosis in Obese Children. Can J Gastroenterol Hepatol. 2018;2018:9465784. Published 2018 Apr 26. doi: 10.1155/2018/9465784
Ubina-Aznar E, Tapia-Ceballos L, Rosales-Zabal JM etal. Insulin resistance and the metabolic syndrome are related to the severity of steatosis in the pediatric population with obesity. Rev Esp Enferm Dig. 2017 Nov;109(11):772-777. doi: 10.17235/reed.2017.4898/2017.
He, L., Deng, L., Zhang, Q., et al., Diagnostic Value of CK-18, FGF-21, and Related Biomarker Panel in Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis. Biomed Res Int, 2017:2017.
Arsik I, Frediani JK, Frezza D, et al. Alanine Aminotransferase as a Monitoring Biomarker in Children with Nonalcoholic Fatty Liver Disease: A Secondary Analysis Using TONIC Trial Data. Children (Basel). 2018;5(6):64. Published 2018 May 25. doi: 10.3390/children5060064
UK National Institute for Health and Care Excellence (NICE).Non-alcoholic fatty liver disease (NAFLD): assessment and management. Guideline ng49. July 2016 [Available from: https://www.nice.org. uk/guidance/ng49.
Hudert, CA, Selinski, S, Rudolph, B, et al. Genetic determinants of steatosis and fibrosis progression in paediatric non-alcoholic fatty liver disease. Liver Int. 2019;39:540-556. https://doi.org/10.1111/liv.14006
Di Costanzo A, Pacifico L, Chiesa C et al. Genetic and metabolic predictors of hepatic fat content in a cohort of Italian children with obesity. Pediatr Res. 2019 Apr;85(5):671-677. doi: 10.1038/s41390- 019-0303-1
Mosca, Antonella et al. The Role of Genetic Predisposition, Programing During Fetal Life, Family Conditions, and Post-natal Diet in the Development of Pediatric Fatty Liver Disease The Journal of Pediatrics, Volume 211, 72-77.e4DOI: https://doi.org/10.1016/j.jpeds.2019.04.018
Zusi C, et al. Contribution of a genetic risk score to clinical prediction of hepatic steatosis in obese children and adolescents. Dig Liver Dis (2019), https://doi.org/10.1016/j.dld.2019.05.029
Hartley A, Santos Ferreira DL, Anderson EL, Lawlor DA. Metabolic profiling of adolescent non-alcoholic fatty liver disease. Wellcome Open Res. 2018;3:166. Published 2018 Dec 28. doi: 10.12688/wellcomeopenres.14974.1
Troisi J, Belmonte F, Bisogno A, et al. Metabolomic Salivary Signature of Pediatric Obesity Related Liver Disease and Metabolic Syndrome. Nutrients. 2019;11(2):274. Published 2019 Jan 26. doi: 10.3390/nu11020274
Gawlik A, Shmoish M, Hartmann MF, et al. Steroid metabolomic signature of liver disease in nonsyndromic childhood obesity [published online ahead of print, 2019 May 1]. Endocr Connect. 2019;8 (6):764-771. doi: 10.1530/EC-18-0536
Ling Jianrong, Zhang Yinjie, Zhang Zhihui, et al. Intestinal flora specific changes in children with nonalcoholic fatty liver disease[J]. Chinese Journal of Pediatrics, 2018, 56(11): 850-855. 10.3760/cma.j.issn.0578-1310.2018.11.011
Schwimmer, Jeffrey B. et al. Microbiome Signatures Associated with Steatohepatitis and Moderate to Severe Fibrosis in Children With Nonalcoholic Fatty Liver Disease Gastroenterology, Published online June 2019, DOI: https://doi.org/10.1053/j.gastro.2019.06.028
Stepanov YM, Zavhorodnia NY, Yagmur VB et al Association of nonalcoholic fatty liver disease with small intestine bacterial overgrowth in obese children. Wiad Lek. 2019;72(3):350-356.
Nobili V, Alisi A, Vania A, et al. The pediatric NAFLD fibrosisindex: a predictor of liver fibrosis in children with non-alcoholicfatty liver disease. BMC Med 2009; 7: 21
Nobili V, Parkes J, Bottazzo G, et al. Performance of ELF serummarkers in predicting fibrosis stage in pediatric nonalcoholic fatty liver disease. Gastroenterology 2009; 136: 160-167.
Alkhouri, Naim et al. A Combination of the Pediatric NAFLD Fibrosis Index and Enhanced Liver Fibrosis Test Identifies Children With Fibrosis Clinical Gastroenterology and Hepatology, Volume 9, Issue 2, 150-155.e1
Jackson JA, Konomi JV, Mendoza MV, et al. Performance of fibrosis predictionscores in paediatric non-alcoholic fatty liver disease. J Paediatr Child Health 2018;54 (2):172-6.
Laura Draijer, Marc Benninga & Bart Koot (2019): Pediatric NAFLD: an overview and recent developments in diagnostics and treatment, Expert Review of Gastroenterology & Hepatology, DOI: 10.1080/17474124.2019.1595589
Wang, R, Yang, F, Qing, L, Huang, R, Liu, Q, Li, X. Decreased serum neuregulin 4 levels associated with non-alcoholic fatty liver disease in children with obesity. Clin Obes. 2019; 9:e12289. https://doi.org/10.1111/cob.12289
Mohamed AA, Sabry S, Abdallah AM, et al. Circulating adipokinesin children with nonalcoholic fatty liver disease: possible noninvasive diagnostic markers. Ann Gastroenterol 2017;30: 457-463
Angin Y, Arslan N, Kuralay F. Leptin-toadiponectin ratio in obese adolescents with nonalcoholic fatty liver disease. Turk J Pediatr 2014; 56: 259-266
Flisiak-Jackiewicz M Bobrus-Chociej A Wasilewska N et al. Can hepatokines be regarded as novel non-invasive serum biomarkers of intrahepatic lipid content in obese children? Advances in Medical Sciences (2019)64(2)280-284 DOI: 10.1016/j.advms.2019.02.005
Brunt EM, Janney CG, Di Bisceglie AM, Neuschwander-Tetri BA, Bacon BR (1999) Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol 94:2467-2474
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(6):1313-21
Bedossa P. Utility and appropriateness of the fatty liver inhibition of progression (FLIP) algorithm and steatosis, activity, and fibrosis (SAF) score in the evaluation of biopsies of nonalcoholic fatty liver disease. Hepatology 2014;60(2):565-75
Alkhouri N, De Vito R, Alisi A, Yerian L, Lopez R, Feldstein AE et al (2012) Development and validation of a new histological score for pediatric nonalcoholic fatty liver disease. J Hepatol 57:1312-1318
Saverymuttu, S.H., Joseph, A.E., and Maxwell, J.D., Ultrasound scanning in the detection of hepatic fibrosis and steatosis. Br Med J (Clin Res Ed), 292(6512):1986
Koot, B.G.P. and Nobili, V., Screening for non-alcoholic fatty liver disease in children: do guidelines provide enough guidance? Obes Rev:2017; 18(9)-1050-60
Bohte AE, van Werven JR, Bipat S, et al. The diagnostic accuracy of US, CT, MRI and 1H-MRS for the evaluation of hepatic steatosiscompared with liver biopsy: a meta-analysis. Eur Radiol 2011; 21: 87-97
Shin J, Kim MJ, Shin HJ, et al. Quick assessment with controlled attenuation parameter for hepatic steatosis in children based on MRI-PDFF as the gold standard. BMC Pediatr. 2019;19(1):112. Published 2019 Apr 15. doi: 10.1186/s12887-019-1485-8
Kwon YD, Ko KO, Lim JW, Cheon EJ, Song YH, Yoon JM. Usefulness of Transient Elastography for Non-Invasive Diagnosis of Liver Fibrosis in Pediatric Non-Alcoholic Steatohepatitis. J Korean Med Sci. 2019;34(23):e165. Published 2019 Jun 17. doi: 10.3346/jkms.2019.34.e165
Middleton MS, Van Natta ML, Heba ER, et al. Diagnostic accuracy of magnetic resonance imaging hepatic proton density fat fraction in pediatric nonalcoholic fatty liver disease. Hepatology 2018;67:858-872
Di Martino M, Pacifico L, Bezzi M, et al. Comparison of magneticresonance spectroscopy, proton density fat fraction and histological analysis in the quantification of liver steatosis inchildren and adolescents. World J Gastroenterol 2016; 22: 8812-8819.
Ballestri S, Lonardo A, Romagnoli D, Carulli L, Losi L, Day CP, et al. Ultrasonographic fatty liver indicator, a novel score which rules out NASHand is correlated with metabolic parameters in NAFLD. Liver Int. (2012) 32:1242-52. doi: 10.1111/j.1478-3231.2012.02804.x
Liu H-K, Yang M-C, Su Y-T, Tai C-M, Wei Y-F, Lin I-C and Tsai C-C (2019) Novel Ultrasonographic Fatty Liver Indicator Can Predict Hepatitis in Children With Non-alcoholic Fatty Liver Disease. Front. Pediatr. 6:416. doi: 10.3389/fped.2018.00416