Browse > Article
http://dx.doi.org/10.3345/kjp.2013.56.2.45

Noninvasive diagnosis of pediatric nonalcoholic fatty liver disease  

Yang, Hye Ran (Department of Pediatrics, Seoul National University Bundang Hospital, Seoul National University College of Medicine)
Publication Information
Clinical and Experimental Pediatrics / v.56, no.2, 2013 , pp. 45-51 More about this Journal
Abstract
Because nonalcoholic steatohepatitis can progress towards cirrhosis even in children, early detection of hepatic fibrosis and accurate diagnosis of nonalcoholic fatty liver disease (NAFLD) are important. Although liver biopsy is regarded as the gold standard of diagnosis, its clinical application is somewhat limited in children due to its invasiveness. Noninvasive diagnostic methods, including imaging studies, biomarkers of inflammation, oxidative stress, hepatic apoptosis, hepatic fibrosis, and noninvasive hepatic fibrosis scores have recently been developed for diagnosing the spectrum of NAFLD, particularly the severity of hepatic fibrosis. Although data and validation are still lacking for these noninvasive modalities in the pediatric population, these methods may be applicable for pediatric NAFLD. Therefore, noninvasive imaging studies, biomarkers, and hepatic fibrosis scoring systems may be useful in the detection of hepatic steatosis and the prediction of hepatic fibrosis, even in children with NAFLD.
Keywords
Nonalcoholic fatty liver disease; Fibrosis; Diagnosis; Obesity; Child;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Sepulveda-Flores RN, Vera-Cabrera L, Flores-Gutierrez JP, Maldonado-Garza H, Salinas-Garza R, Zorrilla-Blanco P, et al. Obesity-related non-alcoholic steatohepatitis and TGF-beta1 serum levels in relation to morbid obesity. Ann Hepatol 2002;1:36-9.
2 Miele L, Forgione A, La Torre G, Vero V, Cefalo C, Racco S, et al. Serum levels of hyaluronic acid and tissue metalloproteinase inhibitor-1 combined with age predict the presence of nonalcoholic steatohepatitis in a pilot cohort of subjects with nonalcoholic fatty liver disease. Transl Res 2009;154:194-201.   DOI   ScienceOn
3 Lesmana CR, Hasan I, Budihusodo U, Gani RA, Krisnuhoni E, Akbar N, et al. Diagnostic value of a group of biochemical markers of liver fibrosis in patients with non-alcoholic steatohepatitis. J Dig Dis 2009;10:201-6.   DOI   ScienceOn
4 Loaeza-del-Castillo A, Paz-Pineda F, Oviedo-Cardenas E, Sanchez-Avila F, Vargas-Vorackova F. AST to platelet ratio index (APRI) for the noninvasive evaluation of liver fibrosis. Ann Hepatol 2008; 7:350-7.
5 McGoogan KE, Smith PB, Choi SS, Berman W, Jhaveri R. Performance of the AST-to-platelet ratio index as a noninvasive marker of fibrosis in pediatric patients with chronic viral hepatitis. J Pediatr Gastroenterol Nutr 2010;50:344-6.   DOI   ScienceOn
6 Ratziu V, Massard J, Charlotte F, Messous D, Imbert-Bismut F, Bonyhay L, et al. Diagnostic value of biochemical markers (FibroTest-FibroSURE) for the prediction of liver fibrosis in patients with non-alcoholic fatty liver disease. BMC Gastroenterol 2006;6:6.   DOI
7 Shah AG, Lydecker A, Murray K, Tetri BN, Contos MJ, Sanyal AJ, et al. Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 2009;7:1104-12.   DOI   ScienceOn
8 Friedrich-Rust M, Rosenberg W, Parkes J, Herrmann E, Zeuzem S, Sarrazin C. Comparison of ELF, FibroTest and FibroScan for the non-invasive assessment of liver fibrosis. BMC Gastroenterol 2010;10:103.   DOI   ScienceOn
9 Alkhouri N, Carter-Kent C, Lopez R, Rosenberg WM, Pinzani M, Bedogni G, et al. A combination of the pediatric NAFLD fibrosis index and enhanced liver fibrosis test identifies children with fibrosis. Clin Gastroenterol Hepatol 2011;9:150-5.   DOI   ScienceOn
10 Manco M, Marcellini M, Giannone G, Nobili V. Correlation of serum TNF-alpha levels and histologic liver injury scores in pediatric nonalcoholic fatty liver disease. Am J Clin Pathol 2007;127:954-60.   DOI   ScienceOn
11 Yang HR, Ko JS, Seo JK. Role of tumor necrosis factor-alpha promoter polymorphism and insulin resistance in the development of non-alcoholic fatty liver disease in obese children. Pediatr Gastroenterol Hepatol Nutr 2012;15:44-51.   DOI
12 Lebensztejn DM, Wojtkowska M, Skiba E, Werpachowska I, Tobolczyk J, Kaczmarski M. Serum concentration of adiponectin, leptin and resistin in obese children with non-alcoholic fatty liver disease. Adv Med Sci 2009;54:177-82.
13 Yang HR, Ko JS, Seo JK. The role of adipokines in the pathogenesis of non-alcoholic fatty liver disease in obese children; the relationship between body fat distribution and insulin resistance. Korean J Pediatr Gastroenterol Nutr 2007;10:185-92.
14 Louthan MV, Barve S, McClain CJ, Joshi-Barve S. Decreased serum adiponectin: an early event in pediatric nonalcoholic fatty liver disease. J Pediatr 2005;147:835-8.   DOI   ScienceOn
15 Day CP, James OF. Steatohepatitis: a tale of two "hits"? Gastroenterology 1998;114:842-5.   DOI   ScienceOn
16 Bonnefont-Rousselot D, Ratziu V, Giral P, Charlotte F, Beucler I, Poynard T, et al. Blood oxidative stress markers are unreliable markers of hepatic steatosis. Aliment Pharmacol Ther 2006;23:91-8.   DOI   ScienceOn
17 Bell LN, Molleston JP, Morton MJ, Klipsch A, Saxena R, Vuppalanchi R, et al. Hepatic lipid peroxidation and cytochrome P-450 2E1 in pediatric nonalcoholic fatty liver disease and its subtypes. J Clin Gastroenterol 2011;45:800-7.   DOI   ScienceOn
18 Piemonte F, Petrini S, Gaeta LM, Tozzi G, Bertini E, Devito R, et al. Protein glutathionylation increases in the liver of patients with non-alcoholic fatty liver disease. J Gastroenterol Hepatol 2008;23 (8 Pt 2):e457-64.   DOI   ScienceOn
19 Nobili V, Parola M, Alisi A, Marra F, Piemonte F, Mombello C, et al. Oxidative stress parameters in paediatric non-alcoholic fatty liver disease. Int J Mol Med 2010;26:471-6.
20 Wieckowska A, Zein NN, Yerian LM, Lopez AR, McCullough AJ, Feldstein AE. In vivo assessment of liver cell apoptosis as a novel biomarker of disease severity in nonalcoholic fatty liver disease. Hepatology 2006;44:27-33.
21 Yilmaz Y, Kedrah AE, Ozdogan O. Cytokeratin-18 fragments and biomarkers of the metabolic syndrome in nonalcoholic steatohepatitis. World J Gastroenterol 2009;15:4387-91.   DOI
22 Vos MB, Barve S, Joshi-Barve S, Carew JD, Whitington PF, McClain CJ. Cytokeratin 18, a marker of cell death, is increased in children with suspected nonalcoholic fatty liver disease. J Pediatr Gastroenterol Nutr 2008;47:481-5.   DOI   ScienceOn
23 Fitzpatrick E, Mitry RR, Quaglia A, Hussain MJ, DeBruyne R, Dhawan A. Serum levels of CK18 M30 and leptin are useful predictors of steatohepatitis and fibrosis in paediatric NAFLD. J Pediatr Gastroenterol Nutr 2010;51:500-6.   DOI   ScienceOn
24 Shannon A, Alkhouri N, Carter-Kent C, Monti L, Devito R, Lopez R, et al. Ultrasonographic quantitative estimation of hepatic steatosis in children with NAFLD. J Pediatr Gastroenterol Nutr 2011;53:190-5.   DOI   ScienceOn
25 Loomba R, Sirlin CB, Schwimmer JB, Lavine JE. Advances in pediatric nonalcoholic fatty liver disease. Hepatology 2009;50: 1282-93.   DOI   ScienceOn
26 Patton HM, Lavine JE, Van Natta ML, Schwimmer JB, Kleiner D, Molleston J, et al. Clinical correlates of histopathology in pediatric nonalcoholic steatohepatitis. Gastroenterology 2008; 135:1961-71.   DOI   ScienceOn
27 Carter-Kent C, Yerian LM, Brunt EM, Angulo P, Kohli R, Ling SC, et al. Nonalcoholic steatohepatitis in children: a multicenter clinicopathological study. Hepatology 2009;50:1113-20.   DOI   ScienceOn
28 Park SE, Yang HR, Chang JY, Ko JS, Seo JK, Lee W, et al. Correlation of body mass index, body fat distribution, aminotranferases and computed tomography in obese children with fatty liver. Korean J Pediatr 2005;48:276-83.
29 Park SH, Kim PN, Kim KW, Lee SW, Yoon SE, Park SW, et al. Macrovesicular hepatic steatosis in living liver donors: use of CT for quantitative and qualitative assessment. Radiology 2006;239: 105-12.   DOI   ScienceOn
30 Pacifico L, Martino MD, Catalano C, Panebianco V, Bezzi M, Anania C, et al. T1-weighted dual-echo MRI for fat quantification in pediatric nonalcoholic fatty liver disease. World J Gastroenterol 2011;17:3012-9.   DOI   ScienceOn
31 Charatcharoenwitthaya P, Lindor KD. Role of radiologic modalities in the management of non-alcoholic steatohepatitis. Clin Liver Dis 2007;11:37-54.   DOI   ScienceOn
32 Yoneda M, Yoneda M , Mawatari H, Fujita K, Endo H, Iida H, et al. Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with nonalcoholic fatty liver disease (NAFLD). Dig Liver Dis 2008;40:371-8.   DOI   ScienceOn
33 Georgoff P, Thomasson D, Louie A, Fleischman E, Dutcher L, Mani H, et al. Hydrogen-1 MR spectroscopy for measurement and diagnosis of hepatic steatosis. AJR Am J Roentgenol 2012;199:2-7.   DOI   ScienceOn
34 Nobili V, Vizzutti F, Arena U, Abraldes JG, Marra F, Pietrobattista A, et al. Accuracy and reproducibility of transient elastography for the diagnosis of fibrosis in pediatric nonalcoholic steatohepatitis. Hepatology 2008;48:442-8.
35 Chen J, Talwalkar JA, Yin M, Glaser KJ, Sanderson SO, Ehman RL. Early detection of nonalcoholic steatohepatitis in patients with nonalcoholic fatty liver disease by using MR elastography. Radiology 2011;259:749-56.   DOI   ScienceOn
36 Binkovitz LA, El-Youssef M, Glaser KJ, Yin M, Binkovitz AK, Ehman RL. Pediatric MR elastography of hepatic fibrosis: principles, technique and early clinical experience. Pediatr Radiol 2012;42:402-9.   DOI
37 Vajro P, Lenta S, Socha P, Dhawan A, McKiernan P, Baumann U, 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.   DOI
38 Roberts EA. Pediatric nonalcoholic fatty liver disease (NAFLD): a "growing" problem? J Hepatol 2007;46:1133-42.   DOI   ScienceOn
39 Schwimmer JB, Behling C, Newbury R, Deutsch R, Nievergelt C, Schork NJ, et al. Histopathology of pediatric nonalcoholic fatty liver disease. Hepatology 2005;42:641-9.   DOI   ScienceOn
40 Ko JS, Yoon JM, Yang HR, Myung JK, Kim H, Kang GH, et al. Clinical and histological features of nonalcoholic fatty liver disease in children. Dig Dis Sci 2009;54:2225-30.   DOI   ScienceOn
41 Wieckowska A, McCullough AJ, Feldstein AE. Noninvasive diagnosis and monitoring of nonalcoholic steatohepatitis: present and future. Hepatology 2007;46:582-9.   DOI   ScienceOn
42 Shiha G, Sarin SK, Ibrahim AE, Omata M, Kumar A, Lesmana LA, et al. Liver fibrosis: consensus recommendations of the Asian Pacific Association for the Study of the Liver (APASL). Hepatol Int 2009;3:323-33.   DOI   ScienceOn
43 Torres DM, Harrison SA. Diagnosis and therapy of nonalcoholic steatohepatitis. Gastroenterology 2008;134:1682-98.   DOI   ScienceOn
44 Guha IN, Parkes J, Roderick PR, Harris S, Rosenberg WM. Non-invasive markers associated with liver fibrosis in non-alcoholic fatty liver disease. Gut 2006;55:1650-60.   DOI   ScienceOn
45 Manning DS, Afdhal NH. Diagnosis and quantitation of fibrosis. Gastroenterology 2008;134:1670-81.   DOI   ScienceOn
46 Nobili V, Alkhouri N, Alisi A, Ottino S, Lopez R, Manco M, et al. Retinol-binding protein 4: a promising circulating marker of liver damage in pediatric nonalcoholic fatty liver disease. Clin Gast roenterol Hepatol 2009;7:575-9.   DOI   ScienceOn
47 Nobili V, Alisi A, Torre G, De Vito R, Pietrobattista A, Morino G, et al. Hyaluronic acid predicts hepatic fibrosis in children with nonalcoholic fatty liver disease. Transl Res 2010;156:229-34.   DOI   ScienceOn
48 Iacobellis A, Marcellini M, Andriulli A, Perri F, Leandro G, Devito R, et al. Non invasive evaluation of liver fibrosis in paediatric patients with nonalcoholic steatohepatitis. World J Gastroenterol 2006;12:7821-5.   DOI
49 Yang HR, Kim HR, Kim MJ, Ko JS, Seo JK. Noninvasive parameters and hepatic fibrosis scores in children with nonalcoholic fatty liver disease. World J Gastroenterol 2012;18:1525-30.   DOI   ScienceOn
50 Nobili V, Parkes J, Bottazzo G, Marcellini M, Cross R, Newman D, et al. Performance of ELF serum markers in predicting fibrosis stage in pediatric non-alcoholic fatty liver disease. Gastroenterology 2009;136:160-7.   DOI   ScienceOn
51 Clark JM, Brancati FL, Diehl AM. Nonalcoholic fatty liver disease. Gastroenterology 2002;122:1649-57.   DOI   ScienceOn
52 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.   DOI   ScienceOn
53 Papandreou D, Rousso I, Mavromichalis I. Update on non-alcoholic fatty liver disease in children. Clin Nutr 2007;26:409-15.   DOI   ScienceOn
54 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.   DOI   ScienceOn
55 Ludwig J, Viggiano TR, McGill DB, Oh BJ. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc 1980;55:434-8.
56 Powell EE, Cooksley WG, Hanson R, Searle J, Halliday JW, Powell LW. The natural history of nonalcoholic steatohepatitis: a follow-up study of forty-two patients for up to 21 years. Hepatology 1990;11:74-80.   DOI
57 Molleston JP, White F, Teckman J, Fitzgerald JF. Obese children with steatohepatitis can develop cirrhosis in childhood. Am J Gastroenterol 2002;97:2460-2.   DOI   ScienceOn
58 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.   DOI   ScienceOn
59 Takahashi Y, Fukusato T. Pediatric nonalcoholic fatty liver disease: overview with emphasis on histology. World J Gastroenterol 2010; 16:5280-5.   DOI