Journal List > Korean J Pediatr Gastroenterol Nutr > v.14(3) > 1043506

Seo: Nonalcoholic Fatty Liver Disease in Children

Abstract

Obesity is significantly increasing in Korean adolescents and nonalcoholic fatty liver disease (NAFLD) is soon expected to be the most common chronic liver disease in children. The symptoms of NAFLD run a broad spectrum and NAFLD in children can lead to the development of nonalcoholic steatohepatitis, cirrhosis and end-stage liver disease, hepatocellular carcinoma (HCC), and can increases the risk of type 2 diabetes and cardiovascular disease. Definitive diagnosis can be achieved with liver biopsy. However, recent advances have shown alternative methods of screening and following patients with noninvasive biomarkers and radiologic imaging studies. The histopathology differs between children and adults, and the mechanism is expected to differ as well. Several factors, such as genes and environmental stressors work intricately to produce NAFLD. Promising medications have been reported for the management of NAFLD. However, their therapeutic effectiveness has yet to be determined. Dietary and exercise interventions remain the mainstay of treatment. By maintaining an interest in obesity and NALFD in children, NAFLD should be diagnosed early and appropriate lifestyle changes should be counseled and encouraged.

Figures and Tables

Fig. 1
Schematic for 'Diagnosis of nonalcoholic fatty liver' by Widhalm K and Ghods E. Nonalcoholic fatty liver disease: a challenge for pediatricians. Int J Obes (Lond) 2010;34:1451-67.
kjpgn-14-209-g001

References

1. Mencin AA, Lavine JE. Nonalcoholic fatty liver disease in children. Curr Opin Clin Nutr Metab Care. 2011. 14:151–157.
crossref
2. Alisi A, Locatelli M, Nobili V. Nonalcoholic fatty liver disease in children. Curr Opin Clin Nutr Metab Care. 2010. 13:397–402.
crossref
3. Lindbäck SM, Gabbert C, Johnson BL, Smorodinsky E, Sirlin CB, Garcia N, et al. Pediatric nonalcoholic fatty liver disease: a comprehensive review. Adv Pediatr. 2010. 57:85–140.
crossref
4. Widhalm K, Ghods E. Nonalcoholic fatty liver disease: a challenge for pediatricians. Int J Obes (Lond). 2010. 34:1451–1467.
crossref
5. Ko JS. Nonalcoholic fatty liver disease. Korean J Gastroenterol. 2010. 56:6–14.
crossref
6. Lee KH. Update on non-alcoholic fatty liver disease in children. Korean J Pediatr Gastroenterol Nutr. 2009. 12:Suppl 1. S62–S71.
crossref
7. Seo JW. Obesity in children and adolescents. Korean J Pediatr. 2009. 52:1311–1320.
crossref
8. Oh KW, Jang MJ, Lee NY, Moon JS, Lee CG, Yoo MH, et al. Prevalence and trends in obesity among Korean children and adolescents in 1997 and 2005. Korean J Pediatr. 2008. 51:950–955.
crossref
9. Tannapfel A, Denk H, Dienes HP, Langner C, Schirmacher P, Trauner M, et al. Histopathological diagnosis of non-alcoholic and alcoholic fatty liver disease. Virchows Arch. 2011. 458:511–523.
crossref
10. 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. 138:1357–1364.
crossref
11. Fraser A, Longnecker MP, Lawlor DA. Prevalence of elevated alanine aminotransferase among US adolescents and associated factors: NHANES 1999-2004. Gastroenterology. 2007. 133:1814–1820.
crossref
12. Manco M, Marcellini M, Devito R, Comparcola D, Sartorelli MR, Nobili V. Metabolic syndrome and liver histology in paediatric nonalcoholic steatohepatitis. Int J Obes (Lond). 2008. 32:381–387.
crossref
13. Loomba R, Sirlin CB, Schwimmer JB, Lavine JE. Advances in pediatric nonalcoholic fatty liver disease. Hepatology. 2009. 50:1282–1293.
crossref
14. Hwang SW, Kim DH, Kim HS. Prevalence of the nonalcoholic fatty liver disease in obese children. Korean J Pediatr. 2005. 48:13–20.
15. Nho HN, Kim CR, Uhm JH, Kim JT, Jin SM, Seo JY, et al. The prevalence of obesity and metabolic abnormalities in Korean pediatric population. Korean J Pediatr Gastroenterol Nutr. 2009. 12:207–214.
crossref
16. Park HS, Han JH, Choi KM, Kim SM. Relation between elevated serum alanine aminotransferase and metabolic syndrome in Korean adolescents. Am J Clin Nutr. 2005. 82:1046–1051.
crossref
17. Schwimmer JB, Deutsch R, Kahen T, Lavine JE, Stanley C, Behling C. Prevalence of fatty liver in children and adolescents. Pediatrics. 2006. 118:1388–1393.
crossref
18. Kistler KD, Molleston J, Unalp A, Abrams SH, Behling C, Schwimmer JB. Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN). Symptoms and quality of life in obese children and adolescents with non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2010. 31:396–406.
crossref
19. 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–e565.
crossref
20. Barshop NJ, Francis CS, Schwimmer JB, Lavine JE. Nonalcoholic fatty liver disease as a comorbidity of childhood obesity. Ped Health. 2009. 3:271–281.
crossref
21. Petersen KF, Dufour S, Feng J, Befroy D, Dziura J, Dalla Man C, et al. Increased prevalence of insulin resistance and nonalcoholic fatty liver disease in Asian-Indian men. Proc Natl Acad Sci USA. 2006. 103:18273–18277.
crossref
22. Louthan MV, Theriot JA, Zimmerman E, Stutts JT, McClain CJ. Decreased prevalence of nonalcoholic fatty liver disease in black obese children. J Pediatr Gastroenterol Nutr. 2005. 41:426–429.
crossref
23. 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. 54:2225–2230.
crossref
24. Feldstein AE, Charatcharoenwitthaya P, Treeprasertsuk S, Benson JT, Enders FB, Angulo P. The natural history of nonalcoholic fatty liver disease in children: a follow-up study for up to 20 years. Gut. 2009. 58:1538–1544.
crossref
25. Argo CK, Northup PG, Al-Osaimi AM, Caldwell SH. Systematic review of risk factors for fibrosis progression in nonalcoholic steatohepatitis. J Hepatol. 2009. 51:371–379.
crossref
26. Neuschwander-Tetri BA, Caldwell SH. Nonalcoholic steatohepatitis: summary of an AASLD single topic conference. Hepatology. 2003. 37:1202–1219.
crossref
27. 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. 143:500–505.
crossref
28. Starley BQ, Calcagno CJ, Harrison SA. Nonalcoholic fatty liver disease and hepatocellular carcinoma: a weighty connection. Hepatology. 2010. 51:1820–1832.
crossref
29. Neuschwander-Tetri BA, Clark JM, Bass NM, Van Natta ML, Unalp-Arida A, Tonascia J, et al. Clinical, laboratory and histological associations in adults with nonalcoholic fatty liver disease. Hepatology. 2010. 52:913–924.
crossref
30. Sanyal AJ, Banas C, Sargeant C, Luketic VA, Sterling RK, Stravitz RT, et al. Similarities and differences in outcomes of cirrhosis due to nonalcoholic steatohepatitis and hepatitis C. Hepatology. 2006. 43:682–689.
crossref
31. Caserta CA, Pendino GM, Amante A, Vacalebre C, Fiorillo MT, Surace P, et al. Cardiovascular risk factors, nonalcoholic fatty liver disease, and carotid artery intima-media thickness in an adolescent population in southern Italy. Am J Epidemiol. 2010. 171:1195–1202.
crossref
32. 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. 118:277–283.
crossref
33. Zivkovic AM, German JB, Sanyal AJ. Comparative review of diets for the metabolic syndrome: implications for nonalcoholic fatty liver disease. Am J Clin Nutr. 2007. 86:285–300.
crossref
34. Donnelly KL, Smith CI, Schwarzenberg SJ, Jessurun J, Boldt MD, Parks EJ. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest. 2005. 115:1343–1351.
crossref
35. Kelishadi R, Cook SR, Amra B, Adibi A. Factors associated with insulin resistance and non-alcoholic fatty liver disease among youths. Atherosclerosis. 2009. 204:538–543.
crossref
36. Day CP, James OF. Steatohepatitis: a tale of two "hits"? Gastroenterology. 1998. 114:842–845.
crossref
37. Cole LK, Jacobs RL, Vance DE. Tamoxifen induces triacylglycerol accumulation in the mouse liver by activation of fatty acid synthesis. Hepatology. 2010. 52:1258–1265.
crossref
38. Newbold RR, Padilla-Banks E, Jefferson WN. Environmental estrogens and obesity. Mol Cell Endocrinol. 2009. 304:84–89.
crossref
39. Hu FB, Malik VS. Sugar-sweetened beverages and risk of obesity and type 2 diabetes: epidemiologic evidence. Physiol Behav. 2010. 100:47–54.
crossref
40. Kohli R, Kirby M, Xanthakos SA, Softic S, Feldstein AE, Saxena V, et al. High-fructose, medium chain trans fat diet induces liver fibrosis and elevates plasma coenzyme Q9 in a novel murine model of obesity and nonalcoholic steatohepatitis. Hepatology. 2010. 52:934–944.
crossref
41. Schwimmer JB, Celedon MA, Lavine JE, Salem R, Campbell N, Schork NJ, et al. Heritability of nonalcoholic fatty liver disease. Gastroenterology. 2009. 136:1585–1592.
crossref
42. Tilg H, Moschen A. Update on nonalcoholic fatty liver disease: genes involved in nonalcoholic fatty liver disease and associated inflammation. Curr Opin Clin Nutr Metab Care. 2010. 13:391–396.
crossref
43. Kheirandish-Gozal L, Sans Capdevila O, Kheirandish E, Gozal D. Elevated serum aminotransferase levels in children at risk for obstructive sleep apnea. Chest. 2008. 133:92–99.
crossref
44. Burke JP, Hale DE, Hazuda HP, Stern MP. A quantitative scale of acanthosis nigricans. Diabetes Care. 1999. 22:1655–1659.
crossref
45. 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.
crossref
46. Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, et al. Nonalcoholic Steatohepatitis Clinical Research Network. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005. 41:1313–1321.
crossref
47. Lee SH, Kim HJ, Oh JC, Han HJ, Kim HS, Tchach H, et al. Diagnosis of fatty liver complicated by simple obesity in children: serum ALT and its correlation with abdominal CT and liver biopsy. Korean J Pediatr Gastroenterol Nutr. 1999. 2:153–163.
crossref
48. Jarrar MH, Baranova A, Collantes R, Ranard B, Stepanova M, Bennett C, et al. Adipokines and cytokines in non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2008. 27:412–421.
crossref
49. Patton HM, Lavine JE, Van Natta ML, Schwimmer JB, Kleiner D, Molleston J. Nonalcoholic Steatohepatitis Clinical Research Network. Clinical correlates of histopathology in pediatric nonalcoholic steatohepatitis. Gastroenterology. 2008. 135:1961–1971.
crossref
50. 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 Gastroenterol Hepatol. 2009. 7:575–579.
crossref
51. Feldstein AE, Wieckowska A, Lopez AR, Liu YC, Zein NN, McCullough AJ. Cytokeratin-18 fragment levels as noninvasive biomarkers for nonalcoholic steatohepatitis: a multicenter validation study. Hepatology. 2009. 50:1072–1078.
crossref
52. 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 nonalcoholic fatty liver disease. Gastroenterology. 2009. 136:160–167.
crossref
53. 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. 9:150–155.
crossref
54. Shah AG, Lydecker A, Murray K, Tetri BN, Contos MJ, Sanyal AJ. Nash Clinical Research Network. Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2009. 7:1104–1112.
crossref
55. 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. 50:1113–1120.
crossref
56. Nobili V, Alkhouri N, Bartuli A, Manco M, Lopez R, Alisi A, et al. Severity of liver injury and atherogenic lipid profile in children with nonalcoholic fatty liver disease. Pediatr Res. 2010. 67:665–670.
crossref
57. Patton HM, Yates K, Unalp-Arida A, Behling CA, Huang TT, Rosenthal P, et al. Association between metabolic syndrome and liver histology among children with nonalcoholic fatty liver disease. Am J Gastroenterol. 2010. 105:2093–2102.
crossref
58. Needleman L, Kurtz AB, Rifkin MD, Cooper HS, Pasto ME, Goldberg BB. Sonography of diffuse benign liver disease: accuracy of pattern recognition and grading. AJR Am J Roentgenol. 1986. 146:1011–1015.
crossref
59. Cassidy FH, Yokoo T, Aganovic L, Hanna RF, Bydder M, Middleton MS, et al. Fatty liver disease: MR imaging techniques for the detection and quantification of liver steatosis. Radiographics. 2009. 29:231–260.
crossref
60. Tomita K, Tanimoto A, Irie R, Kikuchi M, Yokoyama H, Teratani T, et al. Evaluating the severity of nonalcoholic steatohepatitis with superparamagnetic iron oxide-enhanced magnetic resonance imaging. J Magn Reson Imaging. 2008. 28:1444–1450.
crossref
61. 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. 48:442–448.
crossref
62. Wong VW, Vergniol J, Wong GL, Abraldes JG, Marra F, Pietrobattista A, et al. Diagnosis of fibrosis and cirrhosis using liver stiffness measurement in nonalcoholic fatty liver disease. Hepatology. 2010. 51:454–462.
crossref
63. Bohte AE, van Werven JR, Bipat S, Stoker J. The diagnostic accuracy of US, CT, MRI and 1H-MRS for the evaluation of hepatic steatosis compared with liver biopsy: a meta-analysis. Eur Radiol. 2011. 21:87–97. Epub 2010 Jul 31.
crossref
64. 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. 53:190–195.
crossref
65. Reinehr T, Schmidt C, Toschke AM, Andler W. Lifestyle intervention in obese children with nonalcoholic fatty liver disease: 2-year follow-up study. Arch Dis Child. 2009. 94:437–442.
crossref
66. Nobili V, Manco M, Devito R, Di Ciommo V, Comparcola D, Sartorelli MR, et al. Lifestyle intervention and antioxidant therapy in children with nonalcoholic fatty liver disease: a randomized, controlled trial. Hepatology. 2008. 48:119–128.
crossref
67. Nobili V, Marcellini M, Devito R, Ciampalini P, Piemonte F, Comparcola D, et al. NAFLD in children: a prospective clinical-pathological study and effect of lifestyle advice. Hepatology. 2006. 44:458–465.
crossref
68. Houmard JA, Tanner CJ, Slentz CA, Duscha BD, McCartney JS, Kraus WE. Effect of the volume and intensity of exercise training on insulin sensitivity. J Appl Physiol. 2004. 96:101–106.
crossref
69. Lavine JE, Schwimmer JB, Van Natta ML, Molleston JP, Murray KF, Rosenthal P, et al. Nonalcoholic Steatohepatitis Clinical Research Network. Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial. JAMA. 2011. 305:1659–1668.
crossref
70. Sanyal AJ, Chalasani N, Kowdley KV, McCullough A, Diehl AM, Bass NM, et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med. 2010. 362:1675–1685.
crossref
71. Lindor KD, Kowdley KV, Heathcote EJ, Harrison ME, Jorgensen R, Angulo P, et al. Ursodeoxycholic acid for treatment of nonalcoholic steatohepatitis: results of a randomized trial. Hepatology. 2004. 39:770–778.
crossref
72. Leuschner UF, Lindenthal B, Herrmann G, Arnold JC, Rössle M, Cordes HJ, et al. NASH Study Group. High-dose ursodeoxycholic acid therapy for nonalcoholic steatohepatitis: a double-blind, randomized, placebo-controlled trial. Hepatology. 2010. 52:472–479.
crossref
73. Ratziu V, de Ledinghen V, Oberti F, Mathurin P, Wartelle-Bladou C, Renou C, et al. A randomized controlled trial of high-dose ursodesoxycholic acid for nonalcoholic steatohepatitis. J Hepatol. 2011. 54:1011–1019.
crossref
74. Nobili V, Bedogni G, Alisi A, Pietrobattista A, Risé P, Galli C, et al. Docosahexaenoic acid supplementation decreases liver fat content in children with non-alcoholic fatty liver disease: double-blind randomised controlled clinical trial. Arch Dis Child. 2011. 96:350–353.
crossref
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