Skip to main content

Advertisement

SpringerLink
Log in

Pediatric Non-alcoholic Fatty Liver Disease

  • Pediatric Gastroenterology (SR Orenstein, Section Editor)
  • Published:
Current Gastroenterology Reports Aims and scope Submit manuscript

Abstract

Childhood obesity has reached epidemic proportions, and by 2012, more than one third of American children were overweight or obese. As a result, increasingly, children are developing complications of obesity including liver disease. In fact, non-alcoholic fatty liver disease is the most common form of chronic liver disease seen in children today. Recently, there has been a burgeoning literature examining the pathogenesis, genetic markers, and role of the microbiome in this disease. On the clinical front, new modalities of diagnosing hepatic steatosis and hepatic fibrosis are being developed to provide non-invasive methods of surveillance in children. Lastly, the mainstay of treatment of pediatric non-alcoholic fatty liver disease (NAFLD) has been largely through lifestyle interventions, namely, dieting and exercise. Currently, there are a number of clinical trials examining novel lifestyle and drug therapies for NAFLD that are registered with the US National Institutes of Health ClinicalTrials.gov website.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Feldstein AE, Charatcharoenwitthaya P, Treeprasertsuk S, et al. The natural history of non-alcoholic fatty liver disease in children: a follow-up study for up to 20 years. Gut. 2009;58(11):1538–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Marzuillo P, Grandone A, Perrone L, et al. Understanding the pathophysiological mechanisms in the pediatric nonalcoholic fatty liver disease: the role of genetics. World J Gastroenterol. 2015;7(11):1439–43.

    Google Scholar 

  3. Marzuillo P, Del Giudice EM, Santoro N. Pediatric non-alcoholic fatty liver disease: new insights and future directions. World J Gastroenterol. 2014;6(4):217–25.

    Google Scholar 

  4. Marzuillo P, Del Giudice EM, Santoro N. Pediatric fatty liver disease: role of ethnicity and genetics. World J Gastroenterol. 2014;20(23):7347–55.

    Article  PubMed  PubMed Central  Google Scholar 

  5. McPherson S, Hardy T, Henderson E, et al. Evidence of NAFLD progression from steatosis to fibrosing steatohepatitis using paired biopsies: implications for prognosis and clinical management. J Hepatol. 2015;62(5):1148–55.

    Article  PubMed  Google Scholar 

  6. Preiss D, Sattar N. Non-alcoholic fatty liver disease: an overview of prevalence, diagnosis, pathogenesis and treatment considerations. Clin Sci. 2008;115(5):141–50.

    Article  CAS  PubMed  Google Scholar 

  7. Younossi ZM, Stepanova M, Rafiq N, et al. Pathologic criteria for nonalcoholic steatohepatitis: interprotocol agreement and ability to predict liver-related mortality. Hepatology. 2011;53(6):1874–82.

    Article  PubMed  Google Scholar 

  8. Schwimmer JB, Behling C, Newbury R, et al. Histopathology of pediatric nonalcoholic fatty liver disease. Hepatology. 2005;42(3):641–9.

    Article  PubMed  Google Scholar 

  9. Molleston JP, White F, Teckman J, et al. Obese children with steatohepatitis can develop cirrhosis in childhood. Am J Gastroenterol. 2002;97(9):2460–2.

    Article  PubMed  Google Scholar 

  10. Angulo P, Kleiner DE, Dam-Larsen S, et al. Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology. 2015;149(2):389–97. Retrospective study demonstrating that hepatic fibrosis is the single most important prognostic marker in NAFLD.

  11. Xanthakos S, Miles L, Bucuvalas J, et al. Histologic spectrum of nonalcoholic fatty liver disease in morbidly obese adolescents. Clin Gastroenterol Hepatol. 2006;4(2):226–32.

    Article  PubMed  Google Scholar 

  12. Loomba R, Sirlin CB, Schwimmer JB, et al. Advances in pediatric nonalcoholic fatty liver disease. Hepatology. 2009;50(4):1282–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Schwimmer JB, McGreal N, Deutsch R, et al. Influence of gender, race, and ethnicity of suspected fatty liver in obese adolescents. Pediatrics. 2005;115(5):e561–656.

    Article  PubMed  Google Scholar 

  14. Schwimmer JB, Deutsch R, Kahen T, et al. Prevalence of fatty liver in children and adolescents. Pediatrics. 2006;118(4):1388–93.

    Article  PubMed  Google Scholar 

  15. Nomura H, Kashiwagi S, Hayashi J, et al. Prevalence of fatty liver in a general population of Okinawa. Jpn Jpn J Med. 1988;27(2):142–9.

    Article  CAS  PubMed  Google Scholar 

  16. Park HS, Han JS, Choi KM, et al. Relation between elevated serum alanine aminotransferase and metabolic syndrome in Korean adolescents. Am J Clin Nutr. 2005;82(5):1046–51.

    CAS  PubMed  Google Scholar 

  17. Kahali B, Halligan B, Spelitoes E. Insights from genome-wide association analyses of nonalcoholic fatty liver disease. Semin Liver Dis. 2015;35(4):375–91.

    Article  PubMed  Google Scholar 

  18. Day CP, James OF. Steatohepatitis: a tale of two “hits”? Gastroenterology. 1998;114(4):842–5.

    Article  CAS  PubMed  Google Scholar 

  19. D’Adamo E, Cali AM, Weiss R, et al. Central role of fatty liver in the pathogenesis of insulin resistance in obese adolescents. Diabetes Care. 2010;33(8):1817–22.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Cali AM, De Oliveira AM, Kim H, et al. Glucose dysregulation and hepatic steatosis in obese adolescents: is there a link? Hepatology. 2009;49(6):1896–903.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Giorgio V, Prono F, Graziano F, et al. Pediatric non alcoholic fatty liver disease: old and new concepts on development, progression, metabolic insight and potential treatment targets. BMC Pediatr. 2013;13(40):1–10.

    Google Scholar 

  22. Zhu L, Baker RD, Baker SS. From multiple hits to multiple therapeutic targets of non-alcoholic fatty liver disease. Curr Drug Targets. 2015;16(12):1272–3.

    Article  CAS  PubMed  Google Scholar 

  23. Tilg H, Moschen AR. Evolution of inflammation in nonalcoholic fatty liver disease: the multiple parallel hits hypothesis. Hepatology. 2010;52(5):1836–46.

    Article  CAS  PubMed  Google Scholar 

  24. Schwimmer JB, Celedone MA, Lavine JE, et al. Heritability of nonalcoholic fatty liver disease. Gastroenterology. 2009;136(5):1585–92.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Loomba R, Schork N, Chen CH, et al. Heritability of hepatic fibrosis and steatosis based on a prospective twin study. Gastroenterology. 2015;149(7):1784–93.

    Article  PubMed  Google Scholar 

  26. Marchesini G, Petta S, Dalle Grave R. Diet, weight loss, and liver health in nonalcoholic fatty liver disease: pathophysiology, evidence, and practice. Hepatology. 2015. doi:10.1002/hep28392. Important review article highlighting the importance of dietary and life style modifications which lead to weight loss and improvement in NAFLD.

  27. Huang Y, He S, Li JZ, et al. A feed-forward loop amplifies nutritional regulation of PNPLA3. Proc Natl Acad Sci U S A. 2010;107(17):7892–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. He S, McPhaul C, Li JZ, et al. A sequence variation (l148M) in PNPLA3 associated with nonalcoholic fatty liver disease disrupts triglyceride hydrolysis. J Biol Chem. 2010;285(9):6706–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Pirazzi C, Adiels M, Burza MA, et al. Patatin-like phospholipase domain-containing 3 (PNPLA3) l148M (rs738409) affects hepatic VLDL secretion in humans and in vitro. J Hepatol. 2012;57(6):1276–82.

    Article  CAS  PubMed  Google Scholar 

  30. Kozlitina J, Smargris E, Stender S, et al. Exome-wide association study identifies a TM6SF2 variant that confers susceptibility to nonalcoholic fatty liver disease. Nat Genet. 2014;46(4):352–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Goffredo M, Caprio S, Feldstein AE, et al. Role of TM6SF2 rs58542926 in the pathogenesis of nonalcoholic pediatric fatty liver disease: a multiethnic study. Hepatology. 2016;63(1):117–25. The role of the single nucleotide polymorphism, rs58542926 in the TM6SF2 gene in pediatric NAFLD.

  32. Arslan N. Obesity, fatty liver disease and intestinal microbiota. World J Gastroenterol. 2014;20(44):16452–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Turnbaugh PJ, Hamady M, Yatsunenko T, et al. A core gut microbiome in obese and lean twins. Nature. 2009;457(7228):480–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Vrieze A, Van Nood E, Holleman F, et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology. 2012;143(4):913–6.

    Article  CAS  PubMed  Google Scholar 

  35. Qin J, Li Y, Cai Z, et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature. 2012;490(7418):55–60.

    Article  CAS  PubMed  Google Scholar 

  36. Boursier J, Mueller O, Barret M, et al. The severity of NAFLD is associated with gut dysbiosis and shift in the metabolic function of the gut microbiota. Hepatology. 2015. doi:10.1002/hep28356. This study examines the role of intestinal dysbiosis in NAFLD.

  37. Schwimmer JB, Deutsch R, Rauch JB, et al. Obesity, insulin resistance, and other clinicopathological correlates of pediatric nonalcoholic fatty liver disease. J Pediatr. 2003;143(4):500–5.

    Article  PubMed  Google Scholar 

  38. Lavine JE, Schwimmer JB. Nonalcoholic fatty liver disease in the pediatric population. Clin Liver Dis. 2004;8(3):549–58.

    Article  PubMed  Google Scholar 

  39. Rashid M, Roberts EA. Nonalcoholic steatohepatitis in children. J Pediatr Gastroenterol Nutr. 2000;30(1):48–53.

    Article  CAS  PubMed  Google Scholar 

  40. Alkhouri N, De Vito R, Alisi A, et al. Development and validation of a new histological score for pediatric non-alcoholic fatty liver disease. J Hepatol. 2012;57(6):1312–8.

    Article  PubMed  Google Scholar 

  41. Barlow SE, Expert Committee. Expert committee recommendations regarding the prevention, assessment, and treatment of child and adolescent overweight and obesity: summary report. Pediatrics. 2007;120(S4):S164–S92.

    Article  PubMed  Google Scholar 

  42. 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(4):1357–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Molleston JP, Schwimmer JB, Yates KP, et al. Histologic abnormalities in children with nonalcoholic fatty liver disease and normal or mildly elevated alanine aminotransferase levels. J Pediatr. 2014;164(4):707–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Kim H, Taksali SE, Dufour S, et al. Comparative MR study of hepatic fat quantification using single-voxel proton spectroscopy, two-point dixon and three-point IDEAL. Magn Reson Med. 2008;59(3):521–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Shannon A, Alkhouri N, Carter-Kent C, et al. Ultrasonographic quantitative estimation of hepatic steatosis in children with nonalcoholic fatty liver disease (NAFLD). J Pediatr Gastroenterol Nutr. 2011;53(2):190–5.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Tiniakos DG, Vos MB, Brunt EM. Nonalcoholic fatty liver disease: pathology and pathogenesis. Annu Rev Pathol. 2010;5:145–71.

    Article  CAS  PubMed  Google Scholar 

  47. Brunt EM. Pathology of nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol. 2010;7(4):195–203.

    Article  PubMed  Google Scholar 

  48. Caldwell S, Ikura Y, Dias D, et al. Hepatocellular ballooning in NASH. J Hepatol. 2010;53(4):719–23.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Lavine JE, Schwimmer JB, Van Natta ML, et al. 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(16):1659–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Sanyal AJ, Chalasani N, Kowdley KV, et al. Piogrlitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med. 2010;362(18):1675–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Carter-Kent C, Yerian LM, Brunt EM, et al. Nonalcoholic steatohepatitis in children: a mutlicenter clinicopathological study. Hepatology. 2009;50(4):1113–20.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Brunt EM, Janney CG, Di Bisceglie AM, et al. Nonalcoholic steatohepatitis:a proposal for grading and staging the histological lesions. Am J Gastroenterol. 1999;94(9):2467–74.

    Article  CAS  PubMed  Google Scholar 

  53. Kleiner DE, Brunt EM, Van Natta ML, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41(6):1313–21.

    Article  PubMed  Google Scholar 

  54. Dezsofi A, Baumann U, Dhawan A, et al. Liver biopsy in children: position paper of the ESPGHAN Hepatology Committee. J Pediatr Gastroenterol Nutr. 2015;60:408–20.

  55. 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(5):700–13. Most updated position statement on the screening and diagnosis of pediatric NAFLD.

  56. Angulo P, Hui JM, Marchesini G, et al. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology. 2007;45:846–54.

  57. 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.

    Article  CAS  PubMed  Google Scholar 

  58. Yang HR, Kim HR, Kim MJ, et al. Noninvasive parameters and hepatic fibrosis scores in children with nonalcoholic fatty liver disease. World J Gastroenterol. 2012;18(13):1525–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Mansoor S, Yerian L, Kohli R, et al. The evaluation of hepatic fibrosis scores in children with nonalcoholic fatty liver disease. Dig Dis Sci. 2015;60(5):1440–7.

    Article  PubMed  Google Scholar 

  60. Nobili V, Alisi A, Vania A, et al. The pediatric NAFLD fibrosis index: a predictor of liver fibrosis in children with non-alcoholic fatty liver disease. BMC Med. 2009;7:21.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Feldstein AE, Alkhouri N, De Vito R, et al. Serum cytokeratin-18 fragment levels are useful biomarkers for nonalcoholic steatohepatitis in children. Am J Gastroenterol. 2013;108:1526–31.

    Article  CAS  PubMed  Google Scholar 

  62. Feldstein AE, Wieckowska A, Lopez R, et al. Cytokeratin-18 fragment levels as noninvasive biomarker for nonalcoholic steatohepatitis: a multicenter validation study. Hepatology. 2009;50(4):1072–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Mandelia C, Collyer E, Mansoor S, et al. Plasma Cytokeratin-18 level as a novel biomarker for liver fibrosis in children with nonalcoholic fatty liver disease. J Pediatr Gastroenterol Nutr. 2016.

  64. Nobili V, Alisi A, Torre G, et al. Hyaluronic acid predicts hepatic fibrosis in children with nonalcoholic fatty liver disease. Transl Res. 2010;156(4):229–34.

    Article  CAS  PubMed  Google Scholar 

  65. Guha IN, Parkes J, Roderick P, et al. Noninvasive markers of fibrosis in nonalcoholic fatty liver disease: validating the European Liver Fibrosis Panel and exploring simple markers. Hepatology. 2008;47(2):455–60.

    Article  PubMed  Google Scholar 

  66. Nobili V, Parkes J, Bottazzo G, et al. Performance of ELF serum markers in predicting fibrosis stage in pediatric non-alcoholic fatty liver disease. Gastroenterology. 2009;136(1):160–7.

    Article  CAS  PubMed  Google Scholar 

  67. Alkhouri N, Carter-Kent C, Lopez R, et al. A combination of the pediatric NAFLD fibrosis index and enhanced liver fibrosis test identifies children with fibrosis. Clin Gastroenterol Hepatol. 2011;9(2):150–5.

    Article  PubMed  Google Scholar 

  68. Stibbe KJ, Verveer C, Francke J, et al. Comparison of non-invasive assessment to diagnose liver fibrosis in chronic hepatitis B and C patients. Scan J Gastroenterol. 2011;46(7–8):962–72.

    Article  CAS  Google Scholar 

  69. deLedinghen V, Le Bail B, Rebouissoux L, et al. Liver stiffness measurement in children using FibroScan: feasibility study and comparison with Fibrotest, aspartate transaminase to platelets ratio index, and liver biopsy. J Pediatr Gastroenterol Nutr. 2007;45(4):443–50.

    Article  Google Scholar 

  70. Goldschmidt I, Streckenbach C, Dingemann C, et al. Application and limitations of transient liver elastography in children. J Pediatr Gastroenterol Nutr. 2013;57(1):109–13.

    Article  PubMed  Google Scholar 

  71. Petta S, Di Marco V, Camma C, et al. Reliability of liver stiffness measurement in non-alcoholic fatty liver disease: the effects of body mass index. Aliment Pharmacol Ther. 2011;33(12):1350–60.

    Article  CAS  PubMed  Google Scholar 

  72. Koh H, Kim S, Kim MJ, et al. Hepatic fat quantification magnetic resonance for monitoring treatment response in pediatric nonalcoholic steatohepatitis. World J Gastroenterol. 2015;21(33):3741–8.

    Article  Google Scholar 

  73. Idilman IS, Keskin O, Celik A, et al. A comparison of liver fat content as determined by magnetic resonance imaging-proton density fat fraction and MRS versus liver histology in non-alcoholic fatty liver disease. Acta Radiol. 2015.

  74. Permutt Z, Le TA, Peterson MR, et al. Correlation between liver histology and novel magnetic resonance imaging in adult patients with non-alcoholic fatty liver disease - MRI accurately quantifies hepatic steatosis in NAFLD. Aliment Pharmacol Ther. 2012;36(1):22–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Schwimmer JB, Middleton MS, Behling C, et al. Magnetic resonance imaging and liver histology as biomarkers of hepatic steatosis in children with nonalcoholic fatty liver disease. Hepatology. 2015;61(6):1887–95.

    Article  CAS  PubMed  Google Scholar 

  76. Achmad E, Yokoo T, Hamilton G, et al. Feasibility of and agreement between MR imaging and spectroscopic estimation of hepatic proton density fat fraction in children with known or suspected nonalcoholic fatty liver disease. Abdom Imaging. 2015;40(8):3084–90.

    Article  PubMed  Google Scholar 

  77. Yin M, Talwalkar JA, Glaser KJ, et al. Assessment of hepatic fibrosis with magnetic resonance elastography. Clin Gastroenterol Hepatol. 2007;5(10):1207–13.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Imajo K, Kessoku T, Honda Y, et al. Magnetic resonance imaging more accurately classifies steatosis and fibrosis in patients with nonalcoholic fatty liver disease than transient elastography. Gastroenterology 2015.

  79. Cui J, Ang B, Haufe W, et al. Comparative diagnostic accuracy of magnetic resonance elastography vs. eight clinical prediction rules for non-invasive diagnosis of advanced fibrosis in biopsy-proven non-alcoholic fatty liver disease: a prospective study. Aliment Pharmacol Ther. 2015;41(12):1271–80.

    Article  CAS  PubMed  Google Scholar 

  80. Venkatesh SK, Yin M, Ehman RL. Magnetic resonance elastography of liver: technique, analysis, and clinical applications. J Magn Reson Imaging. 2013;37(3):544–55.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Xanthakos SA, Podberesky DJ, Serai SD, et al. Use of magnetic resonance elastography to assess hepatic fibrosis in children with chronic liver disease. J Pediatr. 2014;164(1):186–8.

    Article  PubMed  Google Scholar 

  82. Maurantonio M, Ballestri S, Odoardi MR, et al. Treatment of atherogenic liver based on the pathogenesis of nonalcoholic fatty liver disease: a novel approach to reduce cardiovascular risk? Arch Med Res. 2011;42(5):337–53.

    Article  PubMed  Google Scholar 

  83. Nobili V, Manco M, De Vito R, et al. Lifestyle intervention and antioxidant therapy in children with nonalcoholic fatty liver disease: a randomized, controlled trial. Hepatology. 2008;48(1):119–28.

    Article  CAS  PubMed  Google Scholar 

  84. Gidding SS, Dennison BA, Birch LL, et al. Dietary recommendations for children and adolescents: a guide for practitioners: consensus statement from the American Heart Association. Circulation. 2005;112(13):2061–75.

    Article  CAS  PubMed  Google Scholar 

  85. Vajro P, Mandato C, Licenziati MR, et al. Effects of Lactobacillus rhamnosus strain GG in pediatric obesity-related liver disease. J Pediatr Gastroenterol Nutr. 2011;52(6):740–3.

    Article  PubMed  Google Scholar 

  86. Alisi A, Bedogni G, Baviera G, et al. Randomised clinical trial: the beneficial effects of VSL#3 in obese children with non-alcoholic steatohepatitis. Aliment Pharmacol Ther. 2014;39(11):1276–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Loguercio C, Federico A, Tuccillo C, et al. Beneficial effects of a probiotic VSL#3 on parameters of liver dysfunction in chronic liver diseases. J Clin Gastroenterol. 2005;39(6):540–3.

    Article  PubMed  Google Scholar 

  88. Parker HM, Johnson NA, Burdon CA, et al. Omega-3 supplementation and non-alcoholic fatty liver disease: a systematic review and meta-analysis. J Hepatol. 2012;56(4):944–51.

    Article  CAS  PubMed  Google Scholar 

  89. Masteron GS, Plevris JN, Hayes PC. Review article: omega-3 fatty acids - a promising novel therapy for non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2010;31(7):679–392.

    Article  Google Scholar 

  90. Nobili V, Bedogni G, Alisi A, 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(4):350–3.

    Article  PubMed  Google Scholar 

  91. Nobili V, Alisi A, Della Corte C, et al. Docosahexaenoic acid for the treatment of fatty liver: randomised controlled trial in children. Nutr Metab Cardiovasc Dis. 2013;23(11):1066–70.

    Article  CAS  PubMed  Google Scholar 

  92. Janczyk W, Lebensztein D, Wierzbicka-Rucinska A, et al. Omega-3 Fatty acids therapy in children with nonalcoholic Fatty liver disease: a randomized controlled trial. J Pediatr. 2015;166(6):1358–63.

    Article  CAS  PubMed  Google Scholar 

  93. Janczyk W, Socha P, Lebensztein D, et al. Omega-3 fatty acids for treatment of non-alcoholic fatty liver disease: design and rationale of randomized controlled trial. BMC Pediatr. 2013.

  94. Sanyal AJ, Abdelmalek MF, Suzuki A, et al. No significant effects of ethyl-eicosapentanoic acid on histologic features of nonalcoholic steatohepatitis in a phase 2 trial. Gastroenterology. 2014;147(2):374–87.

    Article  Google Scholar 

  95. Scorletti E, Bhatia L, McCormick KG, et al. Effects of purified eicosapentaenoic and docosahexaenoic acids in nonalcoholic fatty liver disease: results from the Welcome* study. Hepatology. 2014;60(4):1211–21.

    Article  CAS  PubMed  Google Scholar 

  96. Lavine JE. Vitamin E, treatment of nonalcoholic steatohepatitis in children: a pilot study. J Pediatr. 2000;136(6):734–8.

    Article  CAS  PubMed  Google Scholar 

  97. Vajro P, Franzese A, Valerio G, et al. Lack of efficacy of ursodeoxycholic acid for the treatment of liver abnormalities in obese children. J Pediatr. 2000;136(6):739–43.

    Article  CAS  PubMed  Google Scholar 

  98. Ratziu V, Giral P, Jacqueminet S, et al. Rosiglitazone for nonalcoholic steatohepatitis: one-year results of the randomized placebo-controlled Fatty Liver Improvement with Rosiglitazone Therapy (FLIRT) Trial. Gastroenterology. 2008;135(1):100–10.

    Article  CAS  PubMed  Google Scholar 

  99. Du J, Ma Y, Yu C, et al. Effects of pentoxifylline on nonalcoholic fatty liver disease: a meta-analysis. World J Gastroenterol. 2014;20(2):569–77.

    Article  PubMed  PubMed Central  Google Scholar 

  100. Zein CO, Yerian LM, Gogate P, et al. Pentoxifylline improves nonalcoholic steatohepatitis: a randomized placebo-controlled trial. Hepatology. 2011;54(5):1610–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Adorini L, Purzanski M, Shapiro D. Farnesoid X receptor targeting to treat nonalcoholic steatohepatitis. Drug Discov Today. 2012;17–18:988–97.

    Article  Google Scholar 

  102. Nobili V, Vajro P, Dezsofi A, et al. Indications and limitations of bariatric intervention in severely obese children and adolescents with and without nonalcoholic steatohepatitis: ESPGHAN Hepatology Committee Position Statement. J Pediatr Gastroenterol Nutr. 2015;60(4):550–61. Consensus statement on the role of bariatric surgery in pediatric NASH.

Download references

Author information

Authors and Affiliations

  1. Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Alfred I duPont Hospital for Children, Wilmington, DE, USA

    Vikas Uppal, Sana Mansoor & Katryn N. Furuya

  2. The Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA

    Vikas Uppal, Sana Mansoor & Katryn N. Furuya

Authors
  1. Vikas Uppal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sana Mansoor
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Katryn N. Furuya
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Katryn N. Furuya.

Ethics declarations

Conflict of Interest

VU and SM declare that they have no conflicts of interest. KNF reports personal fees from Alexion Pharmaceuticals, outside the submitted work.

Human and Animal Rights and Informed Consent

This article does not contain any studies with animal or human subjects performed by authors VU and KNF. With regard to author SM’s research cited in this paper, all procedures in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Additional information

Vikas Uppal and Sana Mansoor are co-first authors

This article is part of the Topical Collection on Pediatric Gastroenterology

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Uppal, V., Mansoor, S. & Furuya, K.N. Pediatric Non-alcoholic Fatty Liver Disease. Curr Gastroenterol Rep 18, 24 (2016). https://doi.org/10.1007/s11894-016-0498-9

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11894-016-0498-9

Keywords

Search

Navigation