Biomarkers in nonalcoholic fatty liver disease

Canadian Journal of Gastroenterology and Hepatology

Volumn 28, Issue 11, 2014, Pages 607-618

  Neuman, Manuela G ^a,b   Cohen, Lawrence B ^c,d   Nanau, Radu M ^a,b  

^a UNIVERSITY OF TORONTO   (Canada)

^b UNIVERSITY OF TORONTO   (Canada)

^c SUNNYBROOK RESEARCH INSTITUTE   (Canada)

^d UNIVERSITY OF TORONTO   (Canada)

Author keywords

Adipokines; Apoptosis; Cytokeratin; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; Noninvasive biomarkers; Th1 Th2; Toll like receptor; Tumour necrosis factor

Indexed keywords

ADIPOCYTOKINE; ADIPONECTIN; APOLIPOPROTEIN A1; APOLIPOPROTEIN B; BIOLOGICAL MARKER; C PEPTIDE; CYTOKERATIN; FATTY ACID; GHRELIN; LEPTIN; TRIACYLGLYCEROL; TUMOR NECROSIS FACTOR ALPHA; CYTOKERATIN 18;

APOPTOSIS; CELL DEATH; CHOLESTEROL BLOOD LEVEL; DISEASE SEVERITY; ETHNIC GROUP; HUMAN; INSULIN RESISTANCE; LIVER FIBROSIS; LIVER FUNCTION TEST; METABOLOMICS; NONALCOHOLIC FATTY LIVER; PROTEOMICS; REVIEW; SEX DIFFERENCE; BLOOD; ECHOGRAPHY; ENZYMOLOGY; LIVER CIRRHOSIS; OXIDATIVE STRESS;

ADIPONECTIN; BIOMARKERS; GHRELIN; HUMANS; KERATIN-18; LEPTIN; LIVER CIRRHOSIS; LIVER FUNCTION TESTS; METABOLOMICS; NON-ALCOHOLIC FATTY LIVER DISEASE; OXIDATIVE STRESS; PROTEOMICS;

EID: 84914677107     PISSN: 22912789     EISSN: 22912797     Source Type: Journal    
DOI: 10.1155/2014/757929     Document Type: Review

References (147)

1. Adler M, Schaffner F. Fatty liver hepatitis and cirrhosis in obese patients. Am J Med 1979;67:811-6.
2. 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.
3. Bacon BR, Farahvash MJ, Janney CG, Neuschwander-Tetri BA. Nonalcoholic steatohepatitis: An expanded clinical entity. Gastroenterology 1994;107:1103-9.
4. Poonawala A, Nair SP, Thuluvath PJ. Prevalence of obesity and diabetes in patients with cryptogenic cirrhosis: A case-control study. Hepatology 2000;32:689-92.
5. Sanyal AJ, Campbell-Sargent C, Mirshahi F, et al. Nonalcoholic steatohepatitis: Association of insulin resistance and resistance and mitochondrial abnormalities. Gastroeterology 2001;120:1183-92.
6. Popkin BM, Udry JR. Adolescent obesity increases significantly in second and third generation U. S.immigrants: The national longitudinal study of adolescent health. J Nutr 1998;128:701-6.
7. Baldridge AD, Perez-Atayde AR, Graeme-Cook F, Higgins L, Lavine JE. Idopathic steatohepatitis in childhood: A multicenter retrospective study. J Pediatr 1995;127:700-4.
8. Charlton MR, Kondo M, Roberts SK, Steers JL, Krom RA, Wiesner RH. Liver transplantation for crytogenic cirrhosis. Liver Transpl Surg 1997;3:359-64.
9. Czaja AJ. Recurrence of nonalcoholic steatohepatitis after liver transplantation. Liver Transpl Surg 1997;3:185-6.
10. Contos MJ, Cales W, Sterling RK, et al. Development of nonalcoholic fatty liver disease after orthotopic liver transplantation for cryptogenic cirrhosis. Liver Transpl 2001;7:363-73.
11. Keefe EB. Liver transplantation: current status and novel approaches to liver replacement. Gastroenterology 2001;120:749-62.
12. Neuman M, Hilzenrat N, Cohen L, Winkler RE, Nanau R. Multiple factors involved in nonalcoholic hepatitis pathogenesis. Int J Hepatol 2012;2012:429805.
13. Brunt EM, Janney CG, Di Bisceglie AM, Neuschwander-Tetri BA, Bacon BR. Nonalcoholic steatohepatitis: A proposal for grading and staging the histological lesions. Am J Gastroenterol 1999;94:2467-74.
14. Coates RA, Halliday ML, Rankin JG, Feinman S V, Fisher MM. Risk of fatty infiltration or cirrhosis of the liver in relation to ethanol consumption: A case-control study. Clin Invest Med 1986;9:26-32.
15. Angulo P, Lindor KD. Management of nonalcoholic steatohepatitis. In: Krawitt ED, ed. Medical Management of Liver Disease. New York: Marcel Dekker Inc, 1999:367-80.
16. Luyckx FH, Lefebvre PJ, Scheen AJ. Non-alcoholic steatohepatitis: Association with obesity and insulin resistance, and influence of weight loss. Diabetes Metab 2000;26:98-106.
17. Struben VM, Hespenheide EE, Caldwell SH. Nonalcoholic steatohepatitis and cyryptogenic cirrhosis within kindreds. Am J Med 2000;108:9-13.
18. Brunt EM. Nonalcoholic steatohepatitis: Definition and pathology. Semin Liver Dis 2001;21:3-10.
19. Fracanzani AL, Valenti L, Bugianesi E, et al. Risk of severe liver disease in nonalcoholic fatty liver disease with normal aminotransferase levels: A role for insulin resistance and diabetes. Hepatology 2008;48:792-8.
20. Mofrad P, Contos MJ, Haque M, et al. Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values. Hepatology 2003;37:1286-92.
21. Adams LA, Sanderson S, Lindor KD, Angulo P. The histological course of nonalcoholic fatty liver disease: A longitudinal study of 103 patients with sequential liver biopsies. J Hepatol 2005;42:132-8.
22. Mathiesen UL, Frazen LE Fryden A, Foberg U, Bodemar G. The clinical significance of slightly to moderately increases liver transaminase values in asymptomatic patients. Scand J Gastroenterol 1999;34:85-91.
23. Kunde SS, Lazenby AJ, Clements RH, Abrams GA. Spectrum of NAFLD and diagnostic implications of the proposed new normal range for serum ALT in obese women. Hepatology 2005;42:650-6.
24. Kwok R, Tse YK, Wong GL, et al. Systematic review with metaanalysis: Non-invasive assessment of non-alcoholic fatty liver disease - the role of transient elastography and plasma cytokeratin-18 fragments. Aliment Pharmacol Ther 2014;39:254-69.
25. Fitzpatrick E, Mitry RR, Quaglia A, Hussain MJ, De Bruyne 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.
26. Papatheodoridis G V, Hadziyannis E, Tsochatzis E, et al. Serum apoptotic caspase activity in chronic hepatitis C and nonalcoholic fatty liver disease. J Clin Gastroenterol 2010;44:e87-95.
27. Lebensztejn DM, Wierzbicka A, Socha P, et al. Cytokeratin-18 and hyaluronic acid levels predict liver fibrosis in children with nonalcoholic fatty liver disease. Acta Biochim Pol 2011;58:563-6.
28. Tamimi TI, Elgouhari HM, Alkhouri N, et al. An apoptosis panel for nonalcoholic steatohepatitis diagnosis. J Hepatol 2011;54:1224-9.
29. Joka D, Wahl K, Moeller S, et al. Prospective biopsy-controlled evaluation of cell death biomarkers for prediction of liver fibrosis and nonalcoholic steatohepatitis. Hepatology 2012;55:455-64.
30. Shen J, Chan HL, Wong GL, et al. Non-invasive diagnosis of nonalcoholic steatohepatitis by combined serum biomarkers. J Hepatol 2012;56:1363-70.
31. Shen J, Chan HL, Wong GL, et al. Assessment of non-alcoholic fatty liver disease using serum total cell death and apoptosis markers. Aliment Pharmacol Ther 2012;36:1057-66.
32. Feldstein AE, Alkhouri N, De Vito R, Alisi A, Lopez R, Nobili V. Serum cytokeratin-18 fragment levels are useful biomarkers for nonalcoholic steatohepatitis in children. Am J Gastroenterol 2013;108:1526-31.
33. Kim YS, Jung ES, Hur W, et al. Noninvasive predictors of nonalcoholic steatohepatitis in Korean patients with histologically proven nonalcoholic fatty liver disease. Clin Mol Hepatol 2013;19:120-30.
34. Cusi K, Chang Z, Harrison S, et al. Limited value of plasma cytokeratin-18 as a biomarker for NASH and fibrosis in patients with non-alcoholic fatty liver disease. J Hepatol 2014;60:167-74.
35. Grigorescu M, Crisan D, Radu C, Grigorescu MD, Sparchez Z, Serban A. A novel pathophysiological-based panel of biomarkers for the diagnosis of nonalcoholic steatohepatitis. J Physiol Pharmacol 2012;63:347-53.
36. Pirvulescu I, Gheorghe L, Csiki I, et al. Noninvasive clinical model for the diagnosis of nonalcoholic steatohepatitis in overweight and morbidly obese patients undergoing bariatric surgery. Chirurgia (Bucur) 2012;107:772-9.
37. Page S, Birerdinc A, Estep M, et al. Knowledge-based identification of soluble biomarkers: hepatic fibrosis in NAFLD as an example. PLoS One 2013;8:e56009.
38. Guy CD, Suzuki A, Burchette JL, et al. Costaining for keratins 8/18 plus ubiquitin improves detection of hepatocyte injury in nonalcoholic fatty liver disease. Hum Pathol 2012;43:790-800.
39. Skoien R, Richardson MM, Jonsson JR, et al. Heterogeneity of fibrosis patterns in non-alcoholic fatty liver disease supports the presence of multiple fibrogenic pathways. Liver Int 2013;33:624-32.
40. Matsukuma S, Takeo H, Kono T, Nagata Y, Sato K. Aberrant cytokeratin 7 expression of centrilobular hepatocytes: A clinicopathological study. Histopathology 2012;61:857-62.
41. Canbakan B, Senturk H, Canbakan M, et al. Is alanine aminotransferase level a surrogate biomarker of hepatic apoptosis innonalcoholic fatty liver disease? Biomark Med 2010;4:205-14.
42. Armutcu F, Akyol S, Ucar F, Erdogan S, Akyol O. Markers in nonalcoholic steatohepatitis. Adv Clin Chem 2013;61:67-125.
43. Silha J V, Krsek M, Skrha J V, Sucharda P, Nyomba BL, Murphy LJ. Plasma resistin, adiponectin and leptin levels in lean and obese subjects: Correlations with insulin resistance. Eur J Endocrinol 2003;149:331-5.
44. Trujillo ME, Scherer PE. Adiponectin - journey from an adipocyte secretory protein to biomarker of the metabolic syndrome. J Intern Med 2005;257:167-75.
45. Scherer PE, Williams S, Fogliano M, Baldini G, Lodish HF. A novel serum protein similar to C1q, produced exclusively in adipocytes. J Biol Chem 1995;270:26746-9.
46. Hu E, Liang P, Spiegelman BM. AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Biol Chem 1996;271:10697-703.
47. Maeda K, Okubo K, Shimomura I, Funahashi T, Matsuzawa Y, Matsubara K. cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (AdiPose Most abundant Gene transcript 1). Biochem Biophys Res Commun 1996;221:286-9.
48. Shapiro L, Scherer PE. The crystal structure of a complement-1q family protein suggests an evolutionary link to tumor necrosis factor. Curr Biol 1998;8:335-8.
49. Arita Y, Kihara S, Ouchi N, et al. Paradoxical decrease of an adipose - specific protein, adiponectin, in obesity. Biochem Biophys Res Commun 1999;257:79-83.
50. Ouchi N, Kihara S, Arita Y, et al. Novel modulator for endothelial adhesion molecules: Adipocyte-derived plasma protein adiponectin. Circulation 1999;100:2473-6.
51. Hotta K, Funahashi T, Arita Y, et al. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in Type 2 diabetic patients. Arterioscler Thromb Vasc Biol 2000;20:1595-9.
52. Berg AH, Combs TP, Scherer PE. ACRP30/adiponectin: An adipokine regulating glucose and lipid metabolism. Trends Endocrinol Metab 2002;13:84-9.
53. Lindsay RS, Funahashi T, Hanson RL, et al. Adiponectin and development of Type 2 diabetes in the Pima Indian population. Lancet 2002;360:57-8.
54. Matsubara M, Maruoka S, Katayose S. Decreased plasma adiponectin concentrations in women with dyslipidemia. J Clin Endocrinol Metab 2002;87:2764-9.
55. Yang WS, Lee WJ, Funahashi T, et al. Plasma adiponectin levels in overweight and obese Asians. Obes Res 2002;10:1104-10.
56. Beltowski J. Adiponectin and resistin - new hormones of white adipose tissue. Med Sci Monit 2003;9: RA55-61.
57. Yamauchi T, Kamon J, Ito Y, et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 2003;423:762-9.
58. Balmer ML, Joneli J, Schoepfer A, Stickel F, Thormann W, Dufour JF Significance of serum adiponectin levels in patients with chronic liver disease. Clin Sci (Lond) 2010;119:431-6.
59. Gastaldelli A, Harrison S, Belfort-Aguiar R, et al. Pioglitazone in the treatment of NASH: The role of adiponectin. Aliment Pharmacol Ther 2010;32:769-75.
60. Leite NC, Salles GF, Cardoso CR, Villela-Nogueira CA. Serum biomarkers in type 2 diabetic patients with non-alcoholic steatohepatitis and advanced fibrosis. Hepatol Res 2013;43:508-15.
61. Ozcelik F, Yuksel C, Arslan E, Genc S, Omer B, Serdar MA. Relationship between visceral adipose tissue and adiponectin, inflammatorymarkers and thyroid hormones in obese males with hepatosteatosis and insulin resistance. Arch Med Res 2013;44:273-80.
62. Xu YZ, Zhang X, Wang L, et al. An increased circulating angiotensin II concentration is associated with hypoadiponectinemia and postprandial hyperglycemia in men with nonalcoholic fatty liver disease. Intern Med 2013;52:855-61.
63. Zelber-Sagi S, Ratziu V, Zvibel I, et al. The association between adipocytokines and biomarkers for nonalcoholic fatty liver diseaseinduced liver injury: A study in the general population. Eur J Gastroenterol Hepatol 2012;24:262-9.
64. Koehler E, Swain J, Sanderson S, Krishnan A, Watt K, Charlton M. Growth hormone, dehydroepiandrosterone and adiponectin levels in non-alcoholic steatohepatitis: An endocrine signature for advanced fibrosis in obese patients. Liver Int 2012;32:279-86.
65. Polyzos SA, Kountouras J, Anastasilakis AD, Geladari EV, Mantzoros CS. Irisin in patients with nonalcoholic fatty liver disease. Metabolism 2014;63:207-17.
66. Medici V, Ali MR, Seo S, et al. Increased soluble leptin receptor levels in morbidly obese patients with insulin resistance and nonalcoholic fatty liver disease. Obesity (Silver Spring) 2010;18:2268-73.
67. Baranova A, Tran TP, Afendy A, et al. Molecular signature of adipose tissue in patients with both non-alcoholic fatty liver disease (NAFLD) and polycystic ovarian syndrome (PCOS). J Transl Med 2013;11:133.
68. 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;7:737-45.
69. Polyzos SA, Toulis KA, Goulis DG, Zavos C, Kountouras J. Serum total adiponectin in nonalcoholic fatty liver disease: A systematic review and meta-analysis. Metabolism 2011;60:313-26.
70. Bechmann LP, Kocabayoglu P, Sowa JP, et al. Free fatty acids repress small heterodimer partner (SHP) activation and adiponectin counteracts bile acid-induced liver injury in superobese patients with nonalcoholic steatohepatitis. Hepatology 2013;57:1394-406.
71. Bugianesi E, Pagotto U, Manini R, et al. 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;90:3498-504.
72. Carazo A, León J, Casado J, et al. Hepatic expression of adiponectin receptors increases with non-alcoholic fatty liver disease progression in morbid obesity in correlation with glutathione peroxidase 1. Obes Surg 2011;21:492-500.
73. Wong VW, Wong GL, Choi PC, et al. Disease progression of nonalcoholic fatty liver disease: A prospective study with paired liver biopsies at 3 years. Gut 2010;59:969-74.
74. Halaas JL, Gajiwala KS, Maffei M, et al. Weight-reducing effects of the plasma protein encoded by the obese gene. Science 1995;269:543-6.
75. Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature 1998;395:763-70.
76. MacDougald OA, Hwang CS, Fan H, Lane MD. Regulated expression of the obese gene product (leptin) in white adipose tissue and 3T3-L1 adipocytes. Proc Natl Acad Sci U S A 1995;92:9034-7.
77. Rentsch J, Chiesi M. Regulation of ob gene mRNA levels in cultured adipocytes. FEBS Lett 1996;379:55-9.
78. Montague CT, Farooqi IS, Whitehead J P, et al. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 1997;387:903-8.
79. Baratta M. Leptin - from a signal of adiposity to a hormonal mediator in peripheral tissues. Med Sci Monit 2002;8: RA282-92.
80. Considine RV, Sinha MK, Heiman ML, et al. Serum immunoreactive-leptin concentrations in normal weight and obese humans. N Engl J Med 1996;334:292-5.
81. Caro JF, Sinha MK, Kolaczynski JW, Zhang PL, Considine RV. Leptin: the tale of an obesity gene. Diabetes 1996;45:1455-62.
82. Felipo V, Urios A, García-Torres ML, et al. Alterations in adipocytokines and cGMP homeostasis in morbid obesity patients reverse after bariatric surgery. Obesity (Silver Spring) 2013;21:229-37.
83. Machado M V, Coutinho J, Carepa F, Costa A, Proença H, Cortez-Pinto H. How adiponectin, leptin, and ghrelin orchestrate together and correlate with the severity of nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol 2012;24:1166-72.
84. Broglio F, Arvat E, Benso A, et al. Ghrelin: Endocrine and nonendocrine actions. J Pediatr Endocrinol Metab 2002;15(Suppl 5):1219-27.
85. Muccioli G, Tschop M, Papotti M, Deghenghi R, Heiman M, Ghigo E. Neuroendocrine and peripheral activities of ghrelin: Implications in metabolism and obesity. Eur J Pharmacol 2002;440:235-54.
86. Yoshihara F, Kojima M, Hosoda H, Nakazato M, Kangawa K. Ghrelin: A novel peptide for growth hormone release and feeding regulation. Curr Opin Clin Nutr Metab Care 2002;5:391-5.
87. Kojima M, Hosoda H, Matsuo H, Kangawa K. Ghrelin: Discovery of the natural endogenous ligand for the growth hormone secretagogue receptor. Trends Endocrinol Metab 2001;12:118-22.
88. Casanueva F F, Dieguez C. Ghrelin: The link connecting growth with metabolism and energy homeostasis. Rev Endocr Metab Disord 2002;3:325-38.
89. McLaughlin T, Abbasi F, Lamendola C, Frayo RS, Cummings DE. Plasma ghrelin concentrations are decreased in insulin-resistant obese adults relative to equally obese insulin-sensitive controls. J Clin Endocrinol Metab 2004;89:1630-5.
90. Nagaya N, Kojima M, Uematsu M, et al. Hemodynamic and hormonal effects of human ghrelin in healthy volunteers. Am J Physiol: Regul Integr Comp Physiol 2001;280:R1483-7.
91. Soriano-Guillen L, Barrios V, Lechuga-Sancho A, Chowen JA, Argente J. Response of circulating ghrelin levels to insulin therapy in children with newly diagnosed type 1 diabetes mellitus. Pediatr Res 2004;55:830-5.
92. Kim YC, Cho YK, Lee WY, et al. Serum adipocyte-specific fatty acidbinding protein is associated with nonalcoholic fatty liver disease in apparently healthy subjects. J Nutr Biochem 2011;22:289-92.
93. Tomita K, Teratani T, Yokoyama H, et al. Serum immunoglobulin a concentration is an independent predictor of liver fibrosis in nonalcoholic steatohepatitis before the cirrhotic stage. Dig Dis Sci 2011;56:3648-54.
94. Genc H, Dogru T, Kara M, et al. Association of plasma visfatin with hepatic and systemic inflammation in nonalcoholic fatty liver disease. Ann Hepatol 2013;12:548-55.
95. Nobili V, Siotto M, Bedogni G, et al. Levels of serum ceruloplasmin associate with pediatric nonalcoholic fatty liver disease. J Pediatr Gastroenterol Nutr 2013;56:370-5.
96. Kalhan SC, Guo L, Edmison J, et al. Plasma metabolomic profile in nonalcoholic fatty liver disease. Metabolism 2011;60:404-13.
97. Koga M, Saito H, Mukai M, Saibara T, Kasayama S. Serum dehydroepiandrosterone sulphate levels in patients with nonalcoholic fatty liver disease. Intern Med 2011;50:1657-61.
98. Yilmaz Y, Kurt R, Gurdal A, et al. Circulating vaspin levels and epicardial adipose tissue thickness are associated with impaired coronary flow reserve in patients with nonalcoholic fatty liver disease. Atherosclerosis 2011;217:125-9.
99. Yilmaz Y, Yonal O, Eren F, et al. Serum zinc-a2-glycoprotein concentrations in patients with non-alcoholic fatty liver disease. Clin Chem Lab Med 2011;49:93-7.
100. Yilmaz Y, Eren F, Yonal O, et al. Serum progranulin as an independent marker of liver fibrosis in patients with biopsy-proven nonalcoholic fatty liver disease. Dis Markers 2011;31:205-10.
101. Colak Y, Senates E, Ozturk O, et al. Serum concentrations of human insulin-like growth factor-1 and levels of insulin-like growth factor-binding protein-5 in patients with nonalcoholic fatty liver disease: Association with liver histology. Eur J Gastroenterol Hepatol 2012;24:255-61.
102. Dogru T, Genc H, Tapan S, et al. Elevated asymmetric dimethylarginine in plasma: an early marker for endothelial dysfunction in non-alcoholic fatty liver disease? Diabetes Res Clin Pract 2012;96:47-52.
103. Eren F, Kurt R, Ermis F, Atug O, Imeryuz N, Yilmaz Y. Preliminary evidence of a reduced serum level of fibroblast growth factor 19 in patients with biopsy-proven nonalcoholic fatty liver disease. Clin Biochem 2012;45:655-8.
104. Miyazaki M, Kato M, Tanaka K, et al. Increased hepatic expression of dipeptidyl peptidase-4 in non-alcoholic fatty liver disease and its association with insulin resistance and glucose metabolism. Mol Med Rep 2012;5:729-33.
105. Polyzos SA, Kountouras J, Patsiaoura K, et al. Serum homocysteine levels in patients with nonalcoholic fatty liver disease. Ann Hepatol 2012;11:68-76.
106. Kucukazman M, Ata N, Yavuz B, et al. Evaluation of early atherosclerosis markers in patients with nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol 2013;25:147-51.
107. Xu C, Yu C, Ma H, Xu L, Miao M, Li Y. Prevalence and risk factors for the development of nonalcoholic fatty liver disease in a nonobese Chinese population: The Zhejiang Zhenhai Study. Am J Gastroenterol 2013;108:1299-304.
108. Cuthbertson DJ, Irwin A, Pugh CJ, et al. Ectopic lipid storage in Non-Alcoholic Fatty Liver Disease is not mediated by impaired mitochondrial oxidative capacity in skeletal muscle. Clin Sci (Lond) 2014 (In press).
109. Espino A, Villagrán A, Vollrath V, et al. Plasminogen activator inhibitor type 1 serum levels and 4G/5G gene polymorphism in morbidly obese Hispanic patients with non-alcoholic fatty liver disease. Ann Hepatol 2011;10:493-501.
110. Simental-Mendía LE, Rodríguez-Hernández H, Rodríguez-Morán M, Guerrero-Romero F. The alanine aminotransferase to triglycerides ratio as a marker to identify nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol 2012;24:1173-7.
111. Navarro-Jarabo JM, Ubiña-Aznar E, Tapia-Ceballos L, et al. Hepatic steatosis and severity-related factors in obese children. J Gastroenterol Hepatol 2013;28:1532-8.
112. Ballestri S, Meschiari E, Baldelli E, et al. Relationship of serum fetuin-A levels with coronary atherosclerotic burden and NAFLD in patients undergoing elective coronary angiography. Metab Syndr Relat Disord 2013;11:289-95.
113. Manousou P, Kalambokis G, Grillo F, et al. Serum ferritin is a discriminant marker for both fibrosis and inflammation in histologically proven non-alcoholic fatty liver disease patients. Liver Int 2011;31:730-9.
114. Younossi ZM, Page S, Rafiq N, et al. A biomarker panel for non-alcoholic steatohepatitis (NASH) and NASH-related fibrosis. Obes Surg 2011;21:431-9.
115. De Vito R, Alisi A, Masotti A, et al. Markers of activated inflammatory cells correlate with severity of liver damage in children with nonalcoholic fatty liver disease. Int J Mol Med 2012;30:49-56.
116. Mallea-Gil MS, Ballarino MC, Spiraquis A, et al. IGF-1 levels in different stages of liver steatosis and its association with metabolic syndrome. Acta Gastroenterol Latinoam 2012;42:20-6.
117. Pihlajamäki J, Kuulasmaa T, Kaminska D, et al. Serum interleukin 1 receptor antagonist as an independent marker of nonalcoholic steatohepatitis in humans. J Hepatol 2012;56:663-70.
118. Razavizade M, Jamali R, Arj A, Talari H. Serum parameters predict the severity of ultrasonographic findings in non-alcoholic fatty liver disease. Hepatobiliary Pancreat Dis Int 2012;11:513-20.
119. Ogawa Y, Imajo K, Yoneda M, et al. Soluble CD14 levels reflect liver inflammation in patients with nonalcoholic steatohepatitis. PLoS One 2013;8:e65211.
120. Barr J, Vázquez-Chantada M, Alonso C, et al. Liquid chromatography-mass spectrometry-based parallel metabolic profiling of human and mouse model serum reveals putative biomarkers associated with the progression of nonalcoholic fatty liver disease. J Proteome Res 2010;9:4501-12.
121. Soga T, Sugimoto M, Honma M, et al. Serum metabolomics reveals?-glutamyl dipeptides as biomarkers for discrimination among different forms of liver disease. J Hepatol 2011;55:896-905.
122. Li H, Wang L, Yan X, et al. A proton nuclear magnetic resonance metabonomics approach for biomarker discovery in nonalcoholic fatty liver disease. J Proteome Res 2011;10:2797-806.
123. Barr J, Caballería J, Martínez-Arranz I, et al. Obesity-dependent metabolic signatures associated with nonalcoholic fatty liver disease progression. J Proteome Res 2012;11:2521-32.
124. Yu C, Xu C, Xu L, Yu J, Miao M, Li Y. Serum proteomic analysis revealed diagnostic value of hemoglobin for nonalcoholic fatty liver disease. J Hepatol 2012;56:241-7.
125. Miller M, Walsh S, Atirh A, Huang JT, Ferguson MA, Dillon JF. The serum proteome of non-alcoholic fatty liver disease - a multimodal approach to discovery of biomarkers of non-alcoholic steatohepatitis. J Gastroenterol Hepatol 2014 (In press).
126. Naik A, Košir R, Rozman D. Genomic aspects of NAFLD pathogenesis. Genomics 2013;102:84-95.
127. Loomba R, Abraham M, Unalp A, Wilson L, Lavine J, Doo E, Bass NM. Association between diabetes, family history of diabetes, and risk of nonalcoholicsteatohepatitis and fibrosis. Hepatology 2012;56:943-51.
128. Shah AG, Lydecker A, Murray K, Tetri BN, Contos MJ, Sanyal AJ. Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 2009;7:1104-12.
129. Angulo P, Bugianesi E, Bjornsson ES, et al. Simple noninvasive systems predict long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology 2013;145:782-9.e4.
130. Yoneda M, Imajo K, Eguchi Y, et al. Noninvasive scoring systems in patients with nonalcoholic fatty liver disease with normal alanine aminotransferase levels. J Gastroenterol 2013;48:1051-60.
131. Pérez-Gutiérrez OZ, Hernández-Rocha C, Candia-Balboa RA, et al. Validation study of systems for noninvasive diagnosis of fibrosis in nonalcoholic fatty liver disease in Latin population. Ann Hepatol 2013;12:416-24.
132. McPherson S, Stewart S F, Henderson E, Burt AD, Day C P. Simple non-invasive fibrosis scoring systems can reliably exclude advanced fibrosis in patients with non-alcoholic fatty liver disease. Gut 2010;59:1265-9.
133. De Lédinghen V, Vergniol J, Foucher J, Merrouche W, Le Bail B. Non-invasive diagnosis of liver steatosis using controlled attenuation parameter (CAP) and transient elastography. Liver Int 2012;32:911-8.
134. Poynard T, Lassailly G, Diaz E, et al. Performance of biomarkers FibroTest, ActiTest, SteatoTest, and NashTest in patients with severe obesity: meta analysis of individual patient data. PLoS One 2012;7:e30325.
135. Poynard T, Munteanu M, Deckmyn O, et al. Validation of liver fibrosis biomarker (FibroTest) for assessing liver fibrosis progression: Proof of concept and first application in a large population. J Hepatol 2012;57:541-8.
136. Lassailly G, Caiazzo R, Hollebecque A, et al. Validation of noninvasive biomarkers (FibroTest, SteatoTest, and NashTest) for prediction of liver injury in patients with morbid obesity. Eur J Gastroenterol Hepatol 2011;23:499-506.
137. Cao CY, Li YY, Zhou YJ, Nie YQ, Wan YJ. The C-681G polymorphism of the PPAR-γ gene is associated with susceptibility to non-alcoholic fatty liver disease. Tohoku J Exp Med 2012;227:253-62.
138. Alkhouri N, Sedki E, Alisi A, Lopez R, Pinzani M, Feldstein AE, Nobili V. Combined paediatric NAFLD fibrosis index and transient elastography to predict clinically significant fibrosis in children with fatty liver disease. Liver Int 2013;33:79-85.
139. Pirgon Ö, Bilgin H, Çekmez F, Kurku H, Dündar BN. Association between insulin resistance and oxidative stress parameters in obese adolescents with non-alcoholic fatty liver disease. J Clin Res Pediatr Endocrinol 2013;5:33-9.
140. Liu S, Shi W, Li G, et al. Plasma reactive carbonyl species levels and risk of non-alcoholic fatty liver disease. J Gastroenterol Hepatol 2011;26:1010-5.
141. Huang YS, Chang CH, Lin TL, Perng CL. Genetic variations of superoxide dismutase 2 and cytochrome P450 2E1 in non-alcoholic steatohepatitis. Liver Int 2014 (In press).
142. Bell LN, Molleston JP, Morton MJ, 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.
143. Aubert J, Begriche K, Knockaert L, Robin MA, Fromenty B. Increased expression of cytochrome P450 2E1 in nonalcoholic fatty liver disease: Mechanisms and pathophysiological role. Clin Res Hepatol Gastroenterol. 2011;35:630-7.
144. Daly AK. Relevance of CYP2E1 to non-alcoholic fatty liver disease. Subcell Biochem. 2013;67:165-75.
145. Leung TM, Nieto N. CYP2E1 and oxidant stress in alcoholic and non-alcoholic fatty liver disease. J Hepatol 2013;58:395-8.
146. Baker SS, Baker RD, Liu W, Nowak NJ, Zhu L. Role of alcohol metabolism in non-alcoholic steatohepatitis. PLoS One 2010;5:e9570.
147. Chavez A, Hollanda WL, Bar J, Sandhoff K, Summers SA. Acid ceramidase overexpression prevents the inhibitory effects of saturated fatty acid on insulin signaling. J Biol Chem 2005;280:20148-53.