Fatty liver in childhood

World Journal of Hepatology

Volumn 6, Issue 1, 2014, Pages 33-40

  Ozturk, Yesim ^a   Soylu, Ozlem Bekem ^b  

^a DOKUZ EYLUL UNIVERSITY   (Turkey)

^b Behcet Uz Child Disease and Surgery Education and Research Hospital   (Turkey)

Author keywords

Children; Chronic liver disease; Insulin resistance; Metabolic syndrome; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; Obesity

Indexed keywords

EID: 84893709178     PISSN: None     EISSN: 19485182     Source Type: Journal    
DOI: 10.4254/wjh.v6.i1.33     Document Type: Review

References (101)

1. Cohen JC, Horton JD, Hobbs HH. Human fatty liver disease: old questions and new insights. Science 2011; 332: 1519-1523 [PMID: 21700865 DOI: 10.1126/science.1204265]
2. Szczepaniak LS, Nurenberg P, Leonard D, Browning JD, Reingold JS, Grundy S, Hobbs HH, Dobbins RL. Magnetic resonance spectroscopy to measure hepatic triglyceride content: prevalence of hepatic steatosis in the general population. Am J Physiol Endocrinol Metab 2005; 288: E462-E468 [PMID: 15339742 DOI: 10.1152/ajpendo.00064.2004]
3. Ludwig J, Viggiano TR, McGill DB, Oh BJ. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc 1980; 55: 434-438 [PMID: 7382552]
4. Sanyal AJ. Nonalcholic fatty liver disease. In: Yamada T, editor. Textbook of Gastroenterology. 5th ed. Oxford: Blackwell Publishing Ltd, 2009: 2274-2300
5. 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 [PMID: 15864352]
6. Ko JS, Yoon JM, Yang HR, Myung JK, Kim H, Kang GH, Cheon JE, Seo JK. Clinical and histological features of nonalcoholic fatty liver disease in children. Dig Dis Sci 2009; 54: 2225-2230 [PMID: 19697129 DOI: 10.1007/s10620-009-0949-3]
7. 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 [PMID: 17015527 DOI: 10.1542/peds.2006-1212]
8. Schwimmer JB, Behling C, Newbury R, Deutsch R, Nievergelt C, Schork NJ, Lavine JE. Histopathology of pediatric nonalcoholic fatty liver disease. Hepatology 2005; 42: 641-649 [PMID: 16116629 DOI: 10.1002/hep.20842]
9. Barshop NJ, Sirlin CB, Schwimmer JB, Lavine JE. Review article: epidemiology, pathogenesis and potential treatments of paediatric non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2008; 28: 13-24 [PMID: 18397387 DOI: 10.1111/j.1365-2036.2008.03703]
10. Kopec KL, Burns D. Nonalcoholic fatty liver disease: a review of the spectrum of disease, diagnosis, and therapy. Nutr Clin Pract 2011; 26: 565-576 [PMID: 21947639 DOI: 10.1177/0884533611419668]
11. Dunn W, Xu R, Wingard DL, Rogers C, Angulo P, Younossi ZM, Schwimmer JB. Suspected nonalcoholic fatty liver disease and mortality risk in a population-based cohort study. Am J Gastroenterol 2008; 103: 2263-2271 [PMID: 18684196 DOI: 10.1111/j.1572-0241.2008.02034]
12. Quirós-Tejeira RE, Rivera CA, Ziba TT, Mehta N, Smith CW, Butte NF. Risk for nonalcoholic fatty liver disease in Hispanic youth with BMI & gt; or =95th percentile. J Pediatr Gastroenterol Nutr 2007; 44: 228-236 [PMID: 17255837 DOI: 10.1097/MPG.0b013e31802d4acc]
13. Schwimmer JB, Dunn W, Norman GJ, Pardee PE, Middleton MS, Kerkar N, Sirlin CB. SAFETY study: alanine aminotransferase cutoff values are set too high for reliable detection of pediatric chronic liver disease. Gastroenterology 2010; 138: 1357-1364, 1364.e1-2 [PMID: 20064512 DOI: 10.1053/j.gastro.2009.12.052]
14. Arsenault BJ, Beaumont EP, Després JP, Larose E. Mapping body fat distribution: a key step towards the identification of the vulnerable patient? Ann Med 2012; 44: 758-772 [PMID: 22149719 DOI: 10.3109/07853890.2011.605387]
15. Preiss D, Sattar N. Non-alcoholic fatty liver disease: an overview of prevalence, diagnosis, pathogenesis and treatment considerations. Clin Sci (Lond) 2008; 115: 141-150 [PMID: 18662168 DOI: 10.1042/CS20070402]
16. Wong VW, Chu WC, Wong GL, Chan RS, Chim AM, Ong A, Yeung DK, Yiu KK, Chu SH, Woo J, Chan FK, Chan HL. Prevalence of non-alcoholic fatty liver disease and advanced fibrosis in Hong Kong Chinese: a population study using proton-magnetic resonance spectroscopy and transient elastography. Gut 2012; 61: 409-415 [PMID: 21846782 DOI: 10.1136/gutjnl-2011-300342]
17. Argo CK, Caldwell SH. Epidemiology and natural history of non-alcoholic steatohepatitis. Clin Liver Dis 2009; 13: 511-531 [PMID: 19818302 DOI: 10.1016/j.cld.2009.07.005]
18. Starley BQ, Calcagno CJ, Harrison SA. Nonalcoholic fatty liver disease and hepatocellular carcinoma: a weighty connection. Hepatology 2010; 51: 1820-1832 [PMID: 20432259 DOI: 10.1002/hep]
19. Alisi A, Manco M, Vania A, Nobili V. Pediatric nonalcoholic fatty liver disease in 2009. J Pediatr 2009; 155: 469-447 [PMID: 19772998 DOI: 10.1016/j.jpeds.2009.06.014]
20. Mencin AA, Lavine JE. Nonalcoholic fatty liver disease in children. Curr Opin Clin Nutr Metab Care 2011; 14: 151-157 [PMID: 21178608 DOI: 10.1097/MCO.0b013e328342baec]
21. Widhalm K, Ghods E. Nonalcoholic fatty liver disease: a challenge for pediatricians. Int J Obes (Lond) 2010; 34: 1451-1467 [PMID: 20838401 DOI: 10.1038/ijo.2010.185]
22. Roberts EA. Pediatric nonalcoholic fatty liver disease (NAFLD): a "growing" problem? J Hepatol 2007; 46: 1133-1142 [PMID: 17445934 DOI: 10.1016/j.jhep.2007.03.003]
23. Romeo S, Kozlitina J, Xing C, Pertsemlidis A, Cox D, Pennacchio LA, Boerwinkle E, Cohen JC, Hobbs HH. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet 2008; 40: 1461-1465 [PMID: 18820647 DOI: 10.1038/ng.257]
24. Schwimmer JB, Celedon MA, Lavine JE, Salem R, Campbell N, Schork NJ, Shiehmorteza M, Yokoo T, Chavez A, Middleton MS, Sirlin CB. Heritability of nonalcoholic fatty liver disease. Gastroenterology 2009; 136: 1585-1592 [PMID: 19208353 DOI: 10.1053/j.gastro.2009.01.050]
25. Romeo S, Huang-Doran I, Baroni MG, Kotronen A. Unravelling the pathogenesis of fatty liver disease: patatin-like phospholipase domain-containing 3 protein. Curr Opin Lipidol 2010; 21: 247-252 [PMID: 20480550 DOI: 10.1097/MOL.0b013e328338ca61]
26. Deboer MD. Ethnicity, obesity and the metabolic syndrome: implications on assessing risk and targeting intervention. Expert Rev Endocrinol Metab 2011; 6: 279-289 [PMID: 21643518 DOI: 10.1586/eem.11.17]
27. Kong AP, Chow CC. Medical consequences of childhood obesity: a Hong Kong perspective. Res Sports Med 2010; 18: 16-25 [PMID: 20391243 DOI: 10.1080/15438620903413107]
28. Wong VW, Wong GL, Choi PC, Chan AW, Li MK, Chan HY, Chim AM, Yu J, Sung JJ, Chan HL. Disease progression of non-alcoholic fatty liver disease: a prospective study with paired liver biopsies at 3 years. Gut 2010; 59: 969-974 [PMID: 20581244 DOI: 10.1136/gut.2009.205088]
29. Puppala J, Siddapuram SP, Akka J, Munshi A. Genetics of nonalcoholic Fatty liver disease: an overview. J Genet Genomics 2013; 40 : 15-22 [PMID: 23357341 DOI: 10.1016/j.jgg.2012.12.001]
30. Carter-Kent C, Yerian LM, Brunt EM, Angulo P, Kohli R, Ling SC, Xanthakos SA, Whitington PF, Charatcharoenwitthaya P, Yap J, Lopez R, McCullough AJ, Feldstein AE. Nonalcoholic steatohepatitis in children: a multicenter clinicopathological study. Hepatology 2009; 50: 1113-1120 [PMID: 19637190 DOI: 10.1002/hep.23133]
31. 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 [PMID: 14571229 DOI: 10.1067/S0022-3476(03)00325-1]
32. Manton ND, Lipsett J, Moore DJ, Davidson GP, Bourne AJ, Couper RT. Non-alcoholic steatohepatitis in children and adolescents. Med J Aust 2000; 173: 476-479 [PMID: 11149304]
33. Navarro-Jarabo JM, Ubiña-Aznar E, Tapia-Ceballos L, Ortiz-Cuevas C, Pérez-Aísa MA, Rivas-Ruiz F, Andrade RJ, Perea-Milla E. Hepatic steatosis and severity-related factors in obese children. J Gastroenterol Hepatol 2013; 28: 1532-1538 [PMID: 23701491 DOI: 10.1111/jgh.12276]
34. Willner IR, Waters B, Patil SR, Reuben A, Morelli J, Riely CA. Ninety patients with nonalcoholic steatohepatitis: insulin resistance, familial tendency, and severity of disease. Am J Gastroenterol 2001; 96: 2957-2961 [PMID: 11693332 DOI: 10.1111/j.1572-0241.2001.04667.x]
35. Rashid M, Roberts EA. Nonalcoholic steatohepatitis in children. J Pediatr Gastroenterol Nutr 2000; 30: 48-53 [PMID: 10630439 DOI: 10.1097/00005176-200001000-00017]
36. Deboer MD, Wiener RC, Barnes BH, Gurka MJ. Ethnic differences in the link between insulin resistance and elevated ALT. Pediatrics 2013; 132: e718-726 [DOI: 10.1542/peds.2012-3584]
37. Redgrave TG. Formation of cholesteryl ester-rich particulate lipid during metabolism of chylomicrons. J Clin Invest 1970; 49: 465-471 [PMID: 5415674 DOI: 10.1172/JCI106255]
38. Tappy L, Lê KA. Metabolic effects of fructose and the worldwide increase in obesity. Physiol Rev 2010; 90: 23-46 [PMID: 20086073 DOI: 10.1152/physrev.00019.2009]
39. Kusminski CM, Shetty S, Orci L, Unger RH, Scherer PE. Diabetes and apoptosis: lipotoxicity. Apoptosis 2009; 14: 1484-1495 [PMID: 19421860 DOI: 10.1007/s10495-009-0352-8]
40. Unger RH. Minireview: weapons of lean body mass destruction: the role of ectopic lipids in the metabolic syndrome. Endocrinology 2003; 144: 5159-5165 [PMID: 12960011 DOI: 10.1210/en.2003-0870]
41. Ibrahim SH, Kohli R, Gores GJ. Mechanisms of lipotoxicity in NAFLD and clinical implications. J Pediatr Gastroenterol Nutr 2011; 53: 131-140 [PMID: 21629127 DOI: 10.1097/MPG.0b013e31822578db]
42. Brown MS, Goldstein JL. Selective versus total insulin resistance: a pathogenic paradox. Cell Metab 2008; 7: 95-96 [PMID: 18249166 DOI: 10.1016/j.cmet.2007.12.009]
43. Della Corte C, Alisi A, Saccari A, De Vito R, Vania A, Nobili V. Nonalcoholic fatty liver in children and adolescents: an overview. J Adolesc Health 2012; 51: 305-312 [PMID: 22999829 DOI: 10.1016/j.jadohealth.2012.01.010]
44. Nobili V, Svegliati-Baroni G, Alisi A, Miele L, Valenti L, Vajro P. A 360-degree overview of paediatric NAFLD: recent insights. J Hepatol 2013; 58: 1218-1229 [PMID: 23238106 DOI: 10.1016/j.jhep.2012.12.00]
45. Samuel VT, Liu ZX, Qu X, Elder BD, Bilz S, Befroy D, Romanelli AJ, Shulman GI. Mechanism of hepatic insulin resistance in non-alcoholic fatty liver disease. J Biol Chem 2004; 279: 32345-32353 [PMID: 15166226]
46. Tiniakos DG, Vos MB, Brunt EM. Nonalcoholic fatty liver disease: pathology and pathogenesis. Annu Rev Pathol 2010; 5: 145-171 [PMID: 20078219 DOI: 10.1146/annurev-pathol-121808-102132]
47. Frasinariu OE, Ceccarelli S, Alisi A, Moraru E, Nobili V. Gut-liver axis and fibrosis in nonalcoholic fatty liver disease: an input for novel therapies. Dig Liver Dis 2013; 45: 543-551 [PMID: 23280158 DOI: 10.1016/j.dld.2012.11.010]
48. Nobili V, Carpino G, Alisi A, Franchitto A, Alpini G, De Vito R, Onori P, Alvaro D, Gaudio E. Hepatic progenitor cells activation, fibrosis, and adipokines production in pediatric nonalcoholic fatty liver disease. Hepatology 2012; 56: 2142-2153 [PMID: 22467277 DOI: 10.1002/hep.25742]
49. Marra F, Gastaldelli A, Svegliati Baroni G, Tell G, Tiribelli C. Molecular basis and mechanisms of progression of non-alcoholic steatohepatitis. Trends Mol Med 2008; 14: 72-81 [PMID: 18218340 DOI: 10.1016/j.molmed.2007.12.003]
50. Verduci E, Pozzato C, Banderali G, Radaelli G, Arrizza C, Rovere A, Riva E, Giovannini M. Changes of liver fat content and transaminases in obese children after 12-mo nutritional intervention. World J Hepatol 2013; 5: 505-512 [PMID: 24073302 DOI: 10.4254/wjh.v5.i9.505]
51. Berardis S, Sokal E. Pediatric non-alcoholic fatty liver disease: an increasing public health issue. Eur J Pediatr 2013; Epub ahead of print [PMID: 24068459 DOI: 10.1007/s00431-013-2157-6]
52. Nobili V, Cutrera R, Liccardo D, Pavone M, Devito R, Giorgio V, Verrillo E, Baviera G, Musso G. Obstructive sleep apnea syndrome affects liver histology and inflammatory cell activation in pediatric nonalcoholic Fatty liver disease, regardless of obesity/insulin resistance. Am J Respir Crit Care Med 2014; 189: 66-76 [PMID: 24256086 DOI: 10.1164/rccm.201307-1339OC]
53. Roberts EA. Non-alcoholic fatty liver disease (NAFLD) in children. Front Biosci 2005; 10: 2306-2318 [PMID: 15970496 DOI: 10.2741/1699]
54. Ruhl CE, Everhart JE. Determinants of the association of overweight with elevated serum alanine aminotransferase activity in the United States. Gastroenterology 2003; 124: 71-79 [PMID: 12512031 DOI: 10.1053/gast.2003.50004]
55. Sattar N, Scherbakova O, Ford I, O'Reilly DS, Stanley A, Forrest E, Macfarlane PW, Packard CJ, Cobbe SM, Shepherd J. Elevated alanine aminotransferase predicts new-onset type 2 diabetes independently of classical risk factors, metabolic syndrome, and C-reactive protein in the west of Scotland coronary prevention study. Diabetes 2004; 53: 2855-2860 [PMID: 15504965 DOI: 10.2337/diabetes.53.11.2855]
56. Palekar NA, Naus R, Larson SP, Ward J, Harrison SA. Clinical model for distinguishing nonalcoholic steatohepatitis from simple steatosis in patients with nonalcoholic fatty liver disease. Liver Int 2006; 26: 151-156 [PMID: 16448452 DOI: 10.1111/j.1478-3231.2005.01209.x]
57. Pacifico L, Celestre M, Anania C, Paolantonio P, Chiesa C, Laghi A. MRI and ultrasound for hepatic fat quantification: relationships to clinical and metabolic characteristics of pediatric nonalcoholic fatty liver disease. Acta Paediatr 2007; 96: 542-547 [PMID: 17306008 DOI: 10.1111/j.1651-2227.2007.00186.x]
58. Radetti G, Kleon W, Stuefer J, Pittschieler K. Non-alcoholic fatty liver disease in obese children evaluated by magnetic resonance imaging. Acta Paediatr 2006; 95: 833-837 [PMID: 16801180 DOI: 10.1080/08035250500449890]
59. Shimada M, Kawahara H, Ozaki K, Fukura M, Yano H, Tsuchishima M, Tsutsumi M, Takase S. Usefulness of a combined evaluation of the serum adiponectin level, HOMA-IR, and serum type IV collagen 7S level to predict the early stage of nonalcoholic steatohepatitis. Am J Gastroenterol 2007; 102: 1931-1938 [PMID: 17511754 DOI: 10.1111/j.1572-0241.2007.01322.x]
60. Wong VW, Hui AY, Tsang SW, Chan JL, Tse AM, Chan KF, So WY, Cheng AY, Ng WF, Wong GL, Sung JJ, Chan HL. Metabolic and adipokine profile of Chinese patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 2006; 4: 1154-1161 [PMID: 16904946 DOI: 10.1016/j.cgh.2006.06.011]
61. Hui JM, Hodge A, Farrell GC, Kench JG, Kriketos A, George J. Beyond insulin resistance in NASH: TNF-alpha or adiponectin? Hepatology 2004; 40: 46-54 [PMID: 15239085 DOI: 10.1002/hep.20280]
62. Bugianesi E, Pagotto U, Manini R, Vanni E, Gastaldelli A, de Iasio R, Gentilcore E, Natale S, Cassader M, Rizzetto M, Pasquali R, Marchesini G. Plasma adiponectin in nonalcoholic fatty liver is related to hepatic insulin resistance and hepatic fat content, not to liver disease severity. J Clin Endocrinol Metab 2005; 90: 3498-3504 [PMID: 15797948 DOI: 10.1210/jc.2004-2240]
63. Pagano C, Soardo G, Esposito W, Fallo F, Basan L, Donnini D, Federspil G, Sechi LA, Vettor R. Plasma adiponectin is decreased in nonalcoholic fatty liver disease. Eur J Endocrinol 2005; 152: 113-118 [PMID: 15762194 DOI: 10.1530/eje.1.01821]
64. Aygun C, Senturk O, Hulagu S, Uraz S, Celebi A, Konduk T, Mutlu B, Canturk Z. Serum levels of hepatoprotective peptide adiponectin in non-alcoholic fatty liver disease. Eur J Gastroenterol Hepatol 2006; 18: 175-180 [PMID: 16394799 DOI: 10.1097/00042737-200602000-00010]
65. 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: 835-838 [PMID: 16356442 DOI: 10.1016/j.jpeds.2005.07.030]
66. Zou CC, Liang L, Hong F, Fu JF, Zhao ZY. Serum adiponectin, resistin levels and non-alcoholic fatty liver disease in obese children. Endocr J 2005; 52: 519-524 [PMID: 16284427 DOI: 10.1507/endocrj.52.519]
67. Musso G, Gambino R, Biroli G, Carello M, Fagà E, Pacini G, De Michieli F, Cassader M, Durazzo M, Rizzetto M, Pagano G. Hypoadiponectinemia predicts the severity of hepatic fibrosis and pancreatic Beta-cell dysfunction in nondiabetic nonobese patients with nonalcoholic steatohepatitis. Am J Gastroenterol 2005; 100: 2438-2446 [PMID: 16279898 DOI: 10.1111/j.1572-0241.2005.00297.x]
68. Sargin H, Sargin M, Gozu H, Orcun A, Baloglu G, Ozisik M, Seker M, Uygur-Bayramicli O. Is adiponectin level a predictor of nonalcoholic fatty liver disease in nondiabetic male patients? World J Gastroenterol 2005; 11: 5874-5877 [PMID: 16270401]
69. Wong VW, Hui AY, Tsang SW, Chan JL, Wong GL, Chan AW, So WY, Cheng AY, Tong PC, Chan FK, Sung JJ, Chan HL. Prevalence of undiagnosed diabetes and postchallenge hyperglycaemia in Chinese patients with non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2006; 24: 1215-1222 [PMID: 17014580 DOI: 10.1111/j.1365-2036.2006.03112.x]
70. Crespo J, Cayón A, Fernández-Gil P, Hernández-Guerra M, Mayorga M, Domínguez-Díez A, Fernández-Escalante JC, Pons-Romero F. Gene expression of tumor necrosis factor alpha and TNF-receptors, p55 and p75, in nonalcoholic steatohepatitis patients. Hepatology 2001; 34: 1158-1163 [PMID: 11732005 DOI: 10.1053/jhep.2001.29628]
71. Boyraz M, Cekmez F, Karaoglu A, Cinaz P, Durak M, Bideci A. Serum adiponectin, leptin, resistin and RBP4 levels in obese and metabolic syndrome children with nonalcoholic fatty liver disease. Biomark Med 2013; 7: 737-745 [PMID: 24044566 DOI: 10.2217/bmm.13.13]
72. Castera L, Vilgrain V, Angulo P. Noninvasive evaluation of NAFLD. Nat Rev Gastroenterol Hepatol 2013; 10: 666-675 [PMID: 24061203 DOI: 10.1038/nrgastro.2013.175]
73. Joseph AE, Saverymuttu SH, al-Sam S, Cook MG, Maxwell JD. Comparison of liver histology with ultrasonography in assessing diffuse parenchymal liver disease. Clin Radiol 1991; 43: 26-31 [PMID: 1999069 DOI: 10.1016/S0009-9260(05)80350-2]
74. Shannon A, Alkhouri N, Carter-Kent C, Monti L, Devito R, Lopez R, Feldstein AE, Nobili V. Ultrasonographic quantitative estimation of hepatic steatosis in children With NAFLD. J Pediatr Gastroenterol Nutr 2011; 53: 190-195 [PMID: 21788761 DOI: 10.1097/MPG.0b013e31821b4b61]
75. Johnson NA, Walton DW, Sachinwalla T, Thompson CH, Smith K, Ruell PA, Stannard SR, George J. Noninvasive assessment of hepatic lipid composition: Advancing understanding and management of fatty liver disorders. Hepatology 2008; 47: 1513-1523 [PMID: 18393289 DOI: 10.1002/hep.22220]
76. Pearce SG, Thosani NC, Pan JJ. Noninvasive biomarkers for the diagnosis of steatohepatitis and advanced fibrosis in NAFLD. Biomark Res 2013; 1: 7 [PMID: 24252302 DOI: 10.1186/2050-7771-1-7]
77. Wong GL, Wong VW, Choi PC, Chan AW, Chum RH, Chan HK, Lau KK, Chim AM, Yiu KK, Chan FK, Sung JJ, Chan HL. Assessment of fibrosis by transient elastography compared with liver biopsy and morphometry in chronic liver diseases. Clin Gastroenterol Hepatol 2008; 6: 1027-1035 [PMID: 18456573 DOI: 10.1016/j.cgh.2008.02.038]
78. Wong VW, Chan HL. Transient elastography. J Gastroenterol Hepatol 2010; 25: 1726-1731 [PMID: 21039833 DOI: 10.1111/j.1440-1746.2010.06437.x]
79. Nobili V, Vizzutti F, Arena U, Abraldes JG, Marra F, Pietrobattista A, Fruhwirth R, Marcellini M, Pinzani M. Accuracy and reproducibility of transient elastography for the diagnosis of fibrosis in pediatric nonalcoholic steatohepatitis. Hepatology 2008; 48: 442-448 [PMID: 18563842 DOI: 10.1002/hep.22376]
80. Wong VW, Vergniol J, Wong GL, Foucher J, Chan HL, Le Bail B, Choi PC, Kowo M, Chan AW, Merrouche W, Sung JJ, de Lédinghen V. Diagnosis of fibrosis and cirrhosis using liver stiffness measurement in nonalcoholic fatty liver disease. Hepatology 2010; 51: 454-462 [PMID: 20101745 DOI: 10.1002/hep.23312]
81. Xanthakos SA, Podberesky DJ, Serai SD, Miles L, King EC, Balistreri WF, Kohli R. Use of magnetic resonance elastography to assess hepatic fibrosis in children with chronic liver disease. J Pediatr 2014; 164: 186-188 [PMID: 24064151 DOI: 10.1016/j.jpeds.2013.07.050]
82. Lee CK, Perez-Atayde AR, Mitchell PD, Raza R, Afdhal NH, Jonas MM. Serum biomarkers and transient elastography as predictors of advanced liver fibrosis in a United States cohort: the Boston children's hospital experience. J Pediatr 2013; 163: 1058-1064.e2 [PMID: 23759423 DOI: 10.1016/j.jpeds.2013.04.044]
83. Shneider BL, González-Peralta R, Roberts EA. Controversies in the management of pediatric liver disease: Hepatitis B, C and NAFLD: Summary of a single topic conference. Hepatology 2006; 44: 1344-1354 [PMID: 17058223 DOI: 10.1002/hep.21373]
84. Eguchi A, Povero D, Alkhouri N, Feldstein AE. Novel therapeutic targets for nonalcoholic fatty liver disease. Expert Opin Ther Targets 2013; 17: 773-779 [PMID: 23600493 DOI: 10.1517/14728222.2013.789502]
85. Musso G, Gambino R, Cassader M, Pagano G. A meta-analysis of randomized trials for the treatment of nonalcoholic fatty liver disease. Hepatology 2010; 52: 79-104 [PMID: 20578268 DOI: 10.1002/hep.23623]
86. Bell LN, Wang J, Muralidharan S, Chalasani S, Fullenkamp AM, Wilson LA, Sanyal AJ, Kowdley KV, Neuschwander-Tetri BA, Brunt EM, McCullough AJ, Bass NM, Diehl AM, Unalp-Arida A, Chalasani N; Nonalcoholic Steatohepatitis Clinical Research Network. Relationship between adipose tissue insulin resistance and liver histology in nonalcoholic steatohepatitis: apioglitazone versus vitamin E versus placebo for the treatment of nondiabetic patients with nonalcoholicsteatohepatitis trial follow-up study. Hepatology 2012; 56: 1311-1318 [PMID: 22532269 DOI: 10.1002/hep.25805]
87. Dufour JF, Oneta CM, Gonvers JJ, Bihl F, Cerny A, Cereda JM, Zala JF, Helbling B, Steuerwald M, Zimmermann A. Randomized placebo-controlled trial of ursodeoxycholic acid with vitamin e in nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol 2006; 4: 1537-1543 [PMID: 17162245 DOI: 10.1016/j.cgh.2006.09.025]
88. Malaguarnera M, Gargante MP, Russo C, Antic T, Vacante M, Malaguarnera M, Avitabile T, Li Volti G, Galvano F. L-carnitine supplementation to diet: a new tool in treatment of nonalcoholic steatohepatitis--a randomized and controlled clinical trial. Am J Gastroenterol 2010; 105: 1338-1345 [PMID: 20068559 DOI: 10.1038/ajg.2009.719]
89. Lavine JE, Schwimmer JB, Van Natta ML, Molleston JP, Murray KF, Rosenthal P, Abrams SH, Scheimann AO, Sanyal AJ, Chalasani N, Tonascia J, Ünalp A, Clark JM, Brunt EM, Kleiner DE, Hoofnagle JH, Robuck PR. 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 [PMID: 21521847 DOI: 10.1001/jama.2011.520]
90. Ozcan U, Yilmaz E, Ozcan L, Furuhashi M, Vaillancourt E, Smith RO, Görgün CZ, Hotamisligil GS. Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes. Science 2006; 313: 1137-1140 [PMID: 16931765 DOI: 10.1126/science.1128294]
91. Clark JM, Diehl AM. Defining nonalcoholic fatty liver disease: implications for epidemiologic studies. Gastroenterology 2003; 124: 248-250 [PMID: 12512048 DOI: 10.1053/gast.2003.50032]
92. Wei Y, Wang D, Topczewski F, Pagliassotti MJ. Saturated fatty acids induce endoplasmic reticulum stress and apoptosis independently of ceramide in liver cells. Am J Physiol Endocrinol Metab 2006; 291: E275-E281 [PMID: 16492686 DOI: 10.1152/ajpendo.00644.2005]
93. Akazawa Y, Cazanave S, Mott JL, Elmi N, Bronk SF, Kohno S, Charlton MR, Gores GJ. Palmitoleate attenuates palmitate-induced Bim and PUMA up-regulation and hepatocyte lipoapoptosis. J Hepatol 2010; 52: 586-593 [PMID: 20206402 DOI: 10.1016/j.jhep.2010.01.003]
94. Listenberger LL, Han X, Lewis SE, Cases S, Farese RV, Ory DS, Schaffer JE. Triglyceride accumulation protects against fatty acid-induced lipotoxicity. Proc Natl Acad Sci USA 2003; 100: 3077-3082 [PMID: 12629214 DOI: 10.1073/pnas.0630588100]
95. Cho T, Kim YJ, Paik SS. The efficacy of pharmacological treatment in pediatric nonalcoholic Fatty liver disease. Pediatr Gastroenterol Hepatol Nutr 2012; 15: 256-265 [PMID: 24010096 DOI: 10.5223/pghn.2012.15.4.256]
96. Oh MK, Winn J, Poordad F. Review article: diagnosis and treatment of non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2008; 28: 503-522 [PMID: 18532991 DOI: 10.1111/j.1365-2036.2008.03752.x]
97. Bozic MA, Subbarao G, Molleston JP. Pediatric nonalcoholic fatty liver disease. Nutr Clin Pract 2013; 28: 448-458 [PMID: 23917437 DOI: 10.1177/0884533613489153]
98. Schwimmer JB, Newton KP, Awai HI, Choi LJ, Garcia MA, Ellis LL, Vanderwall K, Fontanesi J. Paediatric gastroenterology evaluation of overweight and obese children referred from primary care for suspected non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2013; 38: 1267-1277 [PMID: 24117728 DOI: 10.1111/apt.12518]
99. Ramon-Krauel M, Salsberg SL, Ebbeling CB, Voss SD, Mulkern RV, Apura MM, Cooke EA, Sarao K, Jonas MM, Ludwig DS. A low-glycemic-load versus low-fat diet in the treatment of fatty liver in obese children. Child Obes 2013; 9: 252-260 [PMID: 23705885 DOI: 10.1089/chi.2013]
100. Deldin AR, Lee S. Role of physical activity in the treatment of nonalcoholic fatty liver disease in children and adolescents. Appl Physiol Nutr Metab 2013; 38: 805-812 [PMID: 23855267 DOI: 10.1139/apnm-2012-0503]
101. DeVore S, Kohli R, Lake K, Nicholas L, Dietrich K, Balistreri WF, Xanthakos SA. A multidisciplinary clinical program is effective in stabilizing BMI and reducing transaminase levels in pediatric patients with NAFLD. J Pediatr Gastroenterol Nutr 2013; 57: 119-123 [PMID: 23518484 DOI: 10.1097/MPG.0b013e318290d138]