Common features of the metabolic syndrome and nonalcoholic fatty liver disease

Reviews on Recent Clinical Trials

Volumn 9, Issue 3, 2014, Pages 148-158

  Almeda Valdes, Paloma ^a   Aguilar Olivos, Nancy ^b   Uribe, Misael ^b   Méndez Sánchez, Nahum ^b  

^a INSTITUTO NACIONAL DE CIENCIAS MÉDICAS Y NUTRICIÓN SALVADOR ZUBIRÁN   (Mexico)

^b LIVER RESEARCH UNIT   (Mexico)

Author keywords

Insulin resistance; Metabolic syndrome; Nonalcoholic fatty liver disease; Nonalcoholic Steatohepatitis; Obesity

Indexed keywords

ANTILIPEMIC AGENT; ANTIOXIDANT; GLUCOSE; INSULIN SENSITIZING AGENT;

ACOUSTIC RADIATION FORCE IMPULSE IMAGING; ARTICLE; CARDIOVASCULAR DISEASE; CAUSE OF DEATH; CLINICAL FEATURE; COLON ADENOMA; COMPUTER ASSISTED TOMOGRAPHY; DIET RESTRICTION; DISEASE ASSOCIATION; DISEASE SEVERITY; DYSLIPIDEMIA; ECTOPIC FAT ACCUMULATION; ELASTOGRAPHY; EXERCISE; GLUCOSE BLOOD LEVEL; HUMAN; HYPERFERRITINEMIA; HYPERTRIGLYCERIDEMIA; HYPERURICEMIA; HYPOTHYROIDISM; INSULIN RESISTANCE; LIFESTYLE MODIFICATION; LIPID STORAGE; MEDITERRANEAN DIET; METABOLIC SYNDROME X; NONALCOHOLIC FATTY LIVER; NUCLEAR MAGNETIC RESONANCE IMAGING; OBESITY; OVARY POLYCYSTIC DISEASE; PANCREATIC STEATOSIS; PREVALENCE; PRIORITY JOURNAL; PROTON NUCLEAR MAGNETIC RESONANCE; SLEEP DISORDERED BREATHING; STEATOSIS; VITAMIN D DEFICIENCY; WEIGHT REDUCTION; COMPLICATION; METABOLISM; NON-ALCOHOLIC FATTY LIVER DISEASE;

HUMANS; INSULIN RESISTANCE; METABOLIC SYNDROME X; NON-ALCOHOLIC FATTY LIVER DISEASE;

EID: 84922276214     PISSN: 15748871     EISSN: 18761038     Source Type: Journal    
DOI: 10.2174/1574887109666141216103908     Document Type: Article

References (144)

1. [1] Adams LA, Lindor KD. Nonalcoholic fatty liver disease. Ann of epidemiol 2007; 17: 863-9.
2. [2] Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment pharmacol & thera 2011; 34: 274-85.
3. [3] Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology 2012; 55: 2005-23.
4. [4] Leite NC, Salles GF, Araujo AL, Villela-Nogueira CA, Cardoso CR. Prevalence and associated factors of non-alcoholic fatty liver disease in patients with type-2 diabetes mellitus. Liver international: Offi J Inter Assoc Study Liver 2009; 29: 113-19.
5. [5] Prashanth M, Ganesh HK, Vima MV, et al. Prevalence of nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus. Journal Assoc Physicians India 2009; 57: 205-10.
6. [6] Kalra S, Vithalani M, Gulati G, et al. Study of prevalence of nonalcoholic fatty liver disease (NAFLD) in type 2 diabetes patients in India (SPRINT). J Assoc Physicians India 2013; 61: 448-53.
7. [7] Gholam PM, Flancbaum L, Machan JT, Charney DA, Kotler DP. Nonalcoholic fatty liver disease in severely obese subjects. Am J Gastroenterol 2007; 102: 399-408.
8. [8] Ong JP, Elariny H, Collantes R, et al. Predictors of nonalcoholic steatohepatitis and advanced fibrosis in morbidly obese patients. Obes Sur 2005; 15: 310-5.
9. [9] Assy N, Kaita K, Mymin D, Levy C, Rosser B, Minuk G. Fatty infiltration of liver in hyperlipidemic patients. Diges Dis Sci 2000; 45: 1929-34.
10. [10] Castro-Martinez MG, Banderas-Lares DZ, Ramirez-Martinez JC, Escobedo-de la Pena J. Prevalence of nonalcoholic fatty liver disease in subjects with metabolic syndrome. Cirugia y cirujanos 2012; 80: 128-33.
11. [11] Koehler EM, Schouten JN, Hansen BE, et al. Prevalence and risk factors of non-alcoholic fatty liver disease in the elderly: results from the Rotterdam study. J Hepatol 2012; 57: 1305-11.
12. [12] Lopez-Velazquez JA, Silva-Vidal KV, Ponciano-Rodriguez G, et al. The prevalence of nonalcoholic fatty liver disease in the Americas. Ann Hepatol 2014; 13: 166-78.
13. [13] Marchesini G, Bugianesi E, Forlani G, et al. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology 2003; 37: 917-23.
14. [14] Kissebah AH, Peiris AN. Biology of regional body fat distribution: relationship to non-insulin-dependent diabetes mellitus. Diabetes Metab Rev 1989; 5: 83-109.
15. [15] Sparrow D, Borkan GA, Gerzof SG, Wisniewski C, Silbert CK. Relationship of fat distribution to glucose tolerance. Results of computed tomography in male participants of the Normative Aging Study. Diabetes 1986; 35: 411-5.
16. [16] Despres JP, Moorjani S, Lupien PJ, Tremblay A, Nadeau A, Bouchard C. Regional distribution of body fat, plasma lipoproteins, and cardiovascular disease. Arteriosclerosis 1990; 10: 497-511.
17. [17] Grundy SM, Brewer HB, Jr., Cleeman JI, et al. Definition of metabolic syndrome: Report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation 2004; 109: 433-8.
18. [18] Sanyal AJ, Campbell-Sargent C, Mirshahi F, et al. Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. Gastroenterology 2001; 120: 1183-92.
19. [19] Marchesini G, Brizi M, Bianchi G, et al. Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes 2001; 50: 1844-50.
20. [20] Bugianesi E, Gastaldelli A, Vanni E, et al. Insulin resistance in non-diabetic patients with non-alcoholic fatty liver disease: sites and mechanisms. Diabetologia 2005; 48: 634-42.
21. [21] Kelley DE, McKolanis TM, Hegazi RA, Kuller LH, Kalhan SC. Fatty liver in type 2 diabetes mellitus: relation to regional adiposity, fatty acids, and insulin resistance. Am J Physiol Endocrinol Metab 2003; 285: E906-16.
22. [22] Byrne CD, Targher G. Ectopic fat, insulin resistance, and nonalcoholic Fatty liver disease: implications for cardiovascular disease. Arterioscler Thromb Vasc Biol 2014; 34: 1155-61.
23. [23] Danforth E, Jr. Failure of adipocyte differentiation causes type II diabetes mellitus? Nat Genet 2000; 26: 13.
24. [24] Dowman JK, Tomlinson JW, Newsome PN. Pathogenesis of nonalcoholic fatty liver disease. QJM 2010; 103: 71-83.
25. [25] Bugianesi E, McCullough AJ, Marchesini G. Insulin resistance: a metabolic pathway to chronic liver disease. Hepatology 2005; 42: 987-1000.
26. [26] Magkos F, Su X, Bradley D, et al. Intrahepatic diacylglycerol content is associated with hepatic insulin resistance in obese subjects. Gastroenterology 2012; 142: 1444-1446 e1442.
27. [27] Kumashiro N, Erion DM, Zhang D, et al. Cellular mechanism of insulin resistance in nonalcoholic fatty liver disease. Proc Nat Acad Sci USA 2011; 108: 16381-5.
28. [28] Galbo T, Shulman GI. Lipid-induced hepatic insulin resistance. Aging (Albany NY) 2013; 5: 582-583.
29. [29] Birkenfeld AL, Shulman GI. Nonalcoholic fatty liver disease, hepatic insulin resistance, and type 2 diabetes. Hepatology 2014; 59: 713-23.
30. [30] Hotamisligil GS. Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell 2010; 140: 900-17.
31. [31] Taskinen MR. Diabetic dyslipidaemia: from basic research to clinical practice. Diabetologia 2003; 46: 733-49.
32. [32] Adiels M, Olofsson SO, Taskinen MR, Boren J. Overproduction of very low-density lipoproteins is the hallmark of the dyslipidemia in the metabolic syndrome. Arterioscler Thromb Vasc Biol 2008; 28: 1225-36.
33. [33] Tchernof A, Despres JP. Pathophysiology of human visceral obesity: an update. Physiol Rev 2013; 93: 359-404.
34. [34] Pascot A, Lemieux I, Prud'homme D, et al. Reduced HDL particle size as an additional feature of the atherogenic dyslipidemia of abdominal obesity. J Lipid Res 2001; 42: 2007-14.
35. [35] Lamarche B, Lemieux I, Despres JP. The small, dense LDL phenotype and the risk of coronary heart disease: epidemiology, pathophysiology and therapeutic aspects. Diabetes Metab 1999; 25: 199-211.
36. [36] Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis. Nature 2011; 473: 317-25.
37. [37] Lamarche B, Uffelman KD, Carpentier A, et al. Triglyceride enrichment of HDL enhances in vivo metabolic clearance of HDL apo A-I in healthy men. J Clin Invest 1999; 103: 1191-9.
38. [38] Chirieac DV, Chirieac LR, Corsetti J P, Cianci J, Sparks CE, Sparks JD. Glucose-stimulated insulin secretion suppresses hepatic triglyceride-rich lipoprotein and apoB production. Am J Physiol Endocrinol Metab 2000; 279: E1003-11.
39. [39] Petta S, Muratore C, Craxi A. Non-alcoholic fatty liver disease pathogenesis: the present and the future. Dig Liver Dis 2009; 41: 615-25.
40. [40] Ferre P, Foufelle F. SREBP-1c transcription factor and lipid homeostasis: clinical perspective. Horm Res 2007; 68: 72-82.
41. [41] Pollare T, Vessby B, Lithell H. Lipoprotein lipase activity in skeletal muscle is related to insulin sensitivity. Arterioscler Thromb 1991; 11: 1192-203.
42. [42] Taskinen MR, Adiels M, Westerbacka J, et al. Dual metabolic defects are required to produce hypertriglyceridemia in obese subjects. Arterioscler Thromb Vasc Biol 2011; 31: 2144-50.
43. [43] 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: 1343-51.
44. [44] Kotronen A, Juurinen L, Tiikkainen M, Vehkavaara S, Yki-Jarvinen H. Increased liver fat, impaired insulin clearance, and hepatic and adipose tissue insulin resistance in type 2 diabetes. Gastroenterology 2008; 135: 122-130.
45. [45] Lomonaco R, Ortiz-Lopez C, Orsak B, et al. Effect of adipose tissue insulin resistance on metabolic parameters and liver histology in obese patients with nonalcoholic fatty liver disease. Hepatology 2012; 55: 1389-97.
46. [46] Adams LA, Angulo P, Lindor KD. Nonalcoholic fatty liver disease. CMAJ 2005; 172: 899-905.
47. [47] Schreuder TC, Verwer BJ, van Nieuwkerk CM, Mulder CJ. Nonalcoholic fatty liver disease: an overview of current insights in pathogenesis, diagnosis and treatment. World J Gastroenterol 2008; 14: 2474-86.
48. [48] Trayhurn P. Hypoxia and adipose tissue function and dysfunction in obesity. Physiol Rev 2013; 93: 1-21.
49. [49] Trayhurn P, Wood IS. Signalling role of adipose tissue: adipokines and inflammation in obesity. Biochem Soc Trans 2005; 33: 1078-81.
50. [50] Lumeng CN, Saltiel AR. Inflammatory links between obesity and metabolic disease. J Clin Invest 2011; 121: 2111-7.
51. [51] Skurk T, Alberti-Huber C, Herder C, Hauner H. Relationship between adipocyte size and adipokine expression and secretion. J Clin Endocrinol Metab 2007; 92: 1023-33.
52. [52] Cortez-Pinto H, de Moura MC, Day CP. Non-alcoholic steatohepatitis: from cell biology to clinical practice. J Hepatol 2006; 44: 197-208.
53. [53] Gnacinska M, Malgorzewicz S, Stojek M, Lysiak-Szydlowska W, Sworczak K. Role of adipokines in complications related to obesity: a review. Adv Med Sci 2009; 54: 150-7.
54. [54] Morisset AS, Huot C, Legare D, Tchernof A. Circulating IL-6 concentrations and abdominal adipocyte isoproterenol-stimulated lipolysis in women. Obesity (Silver Spring) 2008; 16: 1487-92.
55. [55] Wieckowska A, Papouchado BG, Li Z, Lopez R, Zein NN, Feldstein AE. Increased hepatic and circulating interleukin-6 levels in human nonalcoholic steatohepatitis. Am J Gastroenterol 2008; 103: 1372-9.
56. [56] Fernandez-Real JM, Vayreda M, Richart C, et al. Circulating interleukin 6 levels, blood pressure, and insulin sensitivity in apparently healthy men and women. J Clin Endocrinol Metab 2001; 86: 1154-9.
57. [57] Berg AH, Combs TP, Scherer PE. ACRP30/adiponectin: an adipokine regulating glucose and lipid metabolism. Trends Endocrinol Metab 2002; 13: 84-9.
58. [58] Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM. Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest 1995; 95: 2409-15.
59. [59] Targher G, Bertolini L, Scala L, Poli F, Zenari L, Falezza G. Decreased plasma adiponectin concentrations are closely associated with nonalcoholic hepatic steatosis in obese individuals. Clin Endocrinol (Oxf) 2004; 61: 700-3.
60. [60] Whitehead JP, Richards AA, Hickman IJ, Macdonald GA, Prins JB. Adiponectin--a key adipokine in the metabolic syndrome. Diabetes Obes Metab 2006; 8: 264-80.
61. [61] Bajaj M, Suraamornkul S, Piper P, et al. Decreased plasma adiponectin concentrations are closely related to hepatic fat content and hepatic insulin resistance in pioglitazone-treated type 2 diabetic patients. J Clin Endocrinol Metab 2004; 89: 200-06.
62. [62] 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.
63. [63] Turer AT, Browning JD, Ayers CR, et al. Adiponectin as an independent predictor of the presence and degree of hepatic steatosis in the Dallas Heart Study. J Clin Endocrinol Metab 2012; 97: E982-6.
64. [64] Musso G, Gambino R, De Michieli F, et al. Dietary habits and their relations to insulin resistance and postprandial lipemia in nonalcoholic steatohepatitis. Hepatology 2003; 37: 909-16.
65. [65] Zelber-Sagi S, Nitzan-Kaluski D, Goldsmith R, et al. Long term nutritional intake and the risk for non-alcoholic fatty liver disease (NAFLD): a population based study. J Hepatol 2007; 47: 711-7.
66. [66] York LW, Puthalapattu S, Wu G Y. Nonalcoholic fatty liver disease and low-carbohydrate diets. Ann Rev Nutr 2009; 29: 365-79.
67. [67] Vos MB, Lavine JE. Dietary fructose in nonalcoholic fatty liver disease. Hepatology 2013; 57: 2525-31.
68. [68] Le KA, Faeh D, Stettler R, et al. A 4-wk high-fructose diet alters lipid metabolism without affecting insulin sensitivity or ectopic lipids in healthy humans. Am J Clin Nutr 2006; 84: 1374-9.
69. [69] Samuel VT. Fructose induced lipogenesis: from sugar to fat to insulin resistance. Trends Endocrinol Metab 2011; 22: 60-5.
70. [70] Ouyang X, Cirillo P, Sautin Y, et al. Fructose consumption as a risk factor for non-alcoholic fatty liver disease. J Hepatol 2008; 48: 993-9.
71. [71] Yamauchi R, Kobayashi M, Matsuda Y, et al. Coffee and caffeine ameliorate hyperglycemia, fatty liver, and inflammatory adipocytokine expression in spontaneously diabetic KK-Ay mice. J Agric Food Chem 2010; 58: 5597-603.
72. [72] Catalano D, Martines GF, Tonzuso A, Pirri C, Trovato FM, Trovato GM. Protective role of coffee in non-alcoholic fatty liver disease (NAFLD). Digestive Dis Sci 2010; 55: 3200-6.
73. [73] Gutierrez-Grobe Y, Chavez-Tapia N, Sanchez-Valle V, et al. High coffee intake is associated with lower grade nonalcoholic fatty liver disease: the role of peripheral antioxidant activity. Ann Hepatol 2012; 11: 350-5.
74. [74] Delgado-Andrade C, Rufian-Henares JA, Morales FJ. Assessing the antioxidant activity of melanoidins from coffee brews by different antioxidant methods. J Agric Food Chem 2005; 53: 7832-6.
75. [75] Alberti KG, Eckel RH, Grundy SM, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 2009; 120: 1640-5.
76. [76] Cameron AJ, Shaw JE, Zimmet PZ. The metabolic syndrome: prevalence in worldwide populations. Endocrinol Metab Clin North Am 2004; 33: 351-75.
77. [77] Mottillo S, Filion KB, Genest J, et al. The metabolic syndrome and cardiovascular risk a systematic review and meta-analysis. J Am Coll Cardiol 2010; 56: 1113-32.
78. [78] Meigs JB, Hu FB, Rifai N, Manson JE. Biomarkers of endothelial dysfunction and risk of type 2 diabetes mellitus. JAMA 2004; 291: 1978-86.
79. [79] Wieckowska A, Feldstein AE. Diagnosis of nonalcoholic fatty liver disease: invasive versus noninvasive. Semin Liver Dis 2008; 28: 386-95.
80. [80] Obika M, Noguchi H. Diagnosis and evaluation of nonalcoholic fatty liver disease. Exper Diabetes Res 2012; 2012: 145754.
81. [81] Sumida Y, Nakajima A, Itoh Y. Limitations of liver biopsy and non-invasive diagnostic tests for the diagnosis of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. World J Gastroenterol 2014; 20: 475-85.
82. [82] Saadeh S, Younossi ZM, Remer EM, et al. The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology 2002; 123: 745-50.
83. [83] Schwenzer NF, Springer F, Schraml C, Stefan N, Machann J, Schick F. Non-invasive assessment and quantification of liver steatosis by ultrasound, computed tomography and magnetic resonance. J Hepatol 2009; 51: 433-45.
84. [84] Yin M, Talwalkar JA, Glaser KJ, et al. Assessment of hepatic fibrosis with magnetic resonance elastography. Clinical gastroenterology and hepatology: the official clinical practice J Am Gastroenterl Assoc 2007; 5: 1207-1213.
85. [85] Abenavoli L, Beaugrand M. Transient elastography in nonalcoholic fatty liver disease. Ann Hepatol 2012; 11: 172-8.
86. [86] Foucher J, Castera L, Bernard PH, et al. Prevalence and factors associated with failure of liver stiffness measurement using FibroScan in a prospective study of 2114 examinations. Eur J Gastroenterol Hepatol 2006; 18: 411-2.
87. [87] Wong VW, Vergniol J, Wong GL, et al. Liver stiffness measurement using XL probe in patients with nonalcoholic fatty liver disease. Am J Gastroenterol 2012; 107: 1862-71.
88. [88] Castera L, Vilgrain V, Angulo P. Noninvasive evaluation of NAFLD. Nat Rev Gastroenterol Hepatol 2013; 10: 666-75.
89. [89] Charatcharoenwitthaya P, Lindor KD. Role of radiologic modalities in the management of non-alcoholic steatohepatitis. Clins Liver Dis 2007; 11: 37-54.
90. [90] Roldan-Valadez E, Favila R, Martinez-Lopez M, Uribe M, Rios C, Mendez-Sanchez N. In vivo 3T spectroscopic quantification of liver fat content in nonalcoholic fatty liver disease: Correlation with biochemical method and morphometry. J Hepatol 2010; 53: 732-7.
91. [91] Polyzos SA, Kountouras J, Papatheodorou A, et al. Adipocytokines and cytokeratin-18 in patients with nonalcoholic fatty liver disease: Introduction of CHA index. Ann Hepatol 2013; 12: 749-57.
92. [92] Caldwell S, Argo C. The natural history of non-alcoholic fatty liver disease. Dig Dis 2010; 28: 162-8.
93. [93] Otgonsuren M, Stepanova M, Gerber L, Younossi ZM. Anthropometric and clinical factors associated with mortality in subjects with nonalcoholic fatty liver disease. Dig Dis Sci 2013; 58: 1132-40.
94. [94] Almeda-Valdes P, Cuevas-Ramos D, Aguilar-Salinas CA. Metabolic syndrome and non-alcoholic fatty liver disease. Ann Hepatol 2009; 8 Suppl 1: S18-24.
95. [95] Karlas T, Wiegand J, Berg T. Gastrointestinal complications of obesity: non-alcoholic fatty liver disease (NAFLD) and its sequelae. Best Prac Res Clin Endocrinol Metab 2013; 27: 195-208.
96. [96] Green RM. NASH--hepatic metabolism and not simply the metabolic syndrome. Hepatology 2003; 38: 14-7.
97. [97] Vanni E, Bugianesi E, Kotronen A, De Minicis S, Yki-Jarvinen H, Svegliati-Baroni G. From the metabolic syndrome to NAFLD or vice versa? Dig Liver Dis 2010; 42: 320-30.
98. [98] Marceau P, Biron S, Hould FS, et al. Liver pathology and the metabolic syndrome X in severe obesity. J Clin Endocrinol Metab 1999; 84: 1513-7.
99. [99] Stone BG, Van Thiel DH. Diabetes mellitus and the liver. Semin Liver Dis 1985; 5: 8-28.
100. [100] Fan JG, Li F, Cai XB, Peng YD, Ao QH, Gao Y. Effects of nonalcoholic fatty liver disease on the development of metabolic disorders. J Gastroenterol Hepatol 2007; 22: 1086-91.
101. [101] Musso G, Gambino R, Cassader M, Pagano G. Meta-analysis: natural history of non-alcoholic fatty liver disease (NAFLD) and diagnostic accuracy of non-invasive tests for liver disease severity. Ann Med 2011; 43: 617-49.
102. [102] Adams LA, Waters OR, Knuiman MW, Elliott RR, Olynyk JK. NAFLD as a risk factor for the development of diabetes and the metabolic syndrome: an eleven-year follow-up study. Am j Gastroenterol 2009; 104: 861-7.
103. [103] Kim HJ, Kim HJ, Lee KE, et al. Metabolic significance of nonalcoholic fatty liver disease in nonobese, nondiabetic adults. Arch Intern Med 2004; 164: 2169-75.
104. [104] Caserta CA, Pendino GM, Amante A, et al. Cardiovascular risk factors, nonalcoholic fatty liver disease, and carotid artery intimamedia thickness in an adolescent population in southern Italy. Am J Epidemiol 2010; 171: 1195-202.
105. [105] Gutierrez-Grobe Y, Gavilanes-Espinar JG, Masso-Rojas FA, et al. Metabolic syndrome and nonalcoholic fatty liver disease. The role of endothelial progenitor cells. Ann Hepatol 2013; 12: 908-14.
106. [106] Targher G, Marra F, Marchesini G. Increased risk of cardiovascular disease in non-alcoholic fatty liver disease: causal effect or epiphenomenon? Diabetologia 2008; 51: 1947-53.
107. [107] Domanski JP, Park SJ, Harrison SA. Cardiovascular disease and nonalcoholic fatty liver disease: does histologic severity matter? J Clin Gastroenterol 2012; 46: 427-30.
108. [108] Daltro C, Cotrim HP, Alves E, et al. Nonalcoholic fatty liver disease associated with obstructive sleep apnea: just a coincidence? Obes Sur 2010; 20: 1536-43.
109. [109] Li Y, Xu C, Yu C, Xu L, Miao M. Association of serum uric acid level with non-alcoholic fatty liver disease: a cross-sectional study. J Hepatol 2009; 50: 1029-34.
110. [110] Matteoni CA, Younossi ZM, Gramlich T, Boparai N, Liu YC, McCullough AJ. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology 1999; 116: 1413-9.
111. [111] Dixon JB, Bhathal PS, O'Brien PE. Nonalcoholic fatty liver disease: predictors of nonalcoholic steatohepatitis and liver fibrosis in the severely obese. Gastroenterology 2001; 121: 91-100.
112. [112] Neuschwander-Tetri BA, Clark JM, Bass NM, et al. Clinical, laboratory and histological associations in adults with nonalcoholic fatty liver disease. Hepatology 2010; 52: 913-24.
113. [113] Dam-Larsen S, Becker U, Franzmann MB, Larsen K, Christoffersen P, Bendtsen F. Final results of a long-term, clinical followup in fatty liver patients. Scand J Gastroenterol 2009; 44: 1236-43.
114. [114] Adams LA, Harmsen S, St Sauver JL, et al. Nonalcoholic fatty liver disease increases risk of death among patients with diabetes: a community-based cohort study. Am J Gastroenterol 2010; 105: 1567-73.
115. [115] Isomaa B, Almgren P, Tuomi T, et al. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 2001; 24: 683-9.
116. [116] Thoma C, Day CP, Trenell MI. Lifestyle interventions for the treatment of non-alcoholic fatty liver disease in adults: a systematic review. J Hepatol 2012; 56: 255-66.
117. [117] Sofi F, Casini A. Mediterranean diet and non-alcoholic fatty liver disease: new therapeutic option around the corner? World J Gastroenterol 2014; 20: 7339-46.
118. [118] Abenavoli L, Milic N. Dietary intervention in non-alcoholic fatty liver disease. J Acad Nutr Diet 2013; 113: 211.
119. [119] Velasco N, Contreras A, Grassi B. The Mediterranean diet, hepatic steatosis and nonalcoholic fatty liver disease. Curr Opin Clin Nutr Metab Care 2014; 17: 453-7.
120. [120] Johnson NA, Sachinwalla T, Walton DW, et al. Aerobic exercise training reduces hepatic and visceral lipids in obese individuals without weight loss. Hepatology 2009; 50: 1105-12.
121. [121] Sreenivasa Baba C, Alexander G, Kalyani B, et al. Effect of exercise and dietary modification on serum aminotransferase levels in patients with nonalcoholic steatohepatitis. J Gastroenterol Hepatol 2006; 21: 191-8.
122. [122] Vilar Gomez E, Rodriguez De Miranda A, Gra Oramas B, et al. Clinical trial: a nutritional supplement Viusid, in combination with diet and exercise, in patients with nonalcoholic fatty liver disease. Aliment pharmacol Ther 2009; 30: 999-1009.
123. [123] Peng L, Wang J, Li F. Weight reduction for non-alcoholic fatty liver disease. Cochrane Database syst Rev 2011: CD003619.
124. [124] Rakoski MO, Singal AG, Rogers MA, Conjeevaram H. Metaanalysis: insulin sensitizers for the treatment of non-alcoholic steatohepatitis. Aliment Pharmacol Ther 2010; 32: 1211-21.
125. [125] Lehmann JM, Moore LB, Smith-Oliver TA, Wilkison WO, Willson TM, Kliewer SA. An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma). J Biol Chem 1995; 270: 12953-6.
126. [126] Sanyal AJ, Chalasani N, Kowdley KV, et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. New Eng J Med 2010; 362: 1675-85.
127. [127] Miller ER, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Inter Med 2005; 142: 37-46.
128. [128] Eslami L, Merat S, Malekzadeh R, Nasseri-Moghaddam S, Aramin H. Statins for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Cochrane Database syst Rev 2013; 12: CD008623.
129. [129] Nakajima K. Multidisciplinary pharmacotherapeutic options for nonalcoholic Fatty liver disease. Int J Hepatol 2012; 2012: 950693.
130. [130] Filippatos TD, Mikhailidis DP. Lipid-lowering drugs acting at the level of the gastrointestinal tract. Curr Pharm Des 2009; 15: 490516.
131. [131] Takeshita Y, Takamura T, Honda M, et al. The effects of ezetimibe on non-alcoholic fatty liver disease and glucose metabolism: a randomised controlled trial. Diabetologia 2014; 57: 878-90.
132. [132] Adorini L, Pruzanski M, Shapiro D. Farnesoid X receptor targeting to treat nonalcoholic steatohepatitis. Drug Disc Today 2012; 17: 988-97.
133. [133] Pellicciari R, Costantino G, Camaioni E, et al. Bile acid derivatives as ligands of the farnesoid X receptor. Synthesis, evaluation, and structure-activity relationship of a series of body and side chain modified analogues of chenodeoxycholic acid. J Med Chem 2004; 47: 4559-69.
134. [134] Mudaliar S, Henry RR, Sanyal AJ, et al. Efficacy and safety of the farnesoid X receptor agonist obeticholic acid in patients with type 2 diabetes and nonalcoholic fatty liver disease. Gastroenterology 2013; 145: 574-582.
135. [135] Mouzaki M, Comelli EM, Arendt BM, et al. Intestinal microbiota in patients with nonalcoholic fatty liver disease. Hepatology 2013; 58: 120-7.
136. [136] Ma X, Hua J, Li Z. Probiotics improve high fat diet-induced hepatic steatosis and insulin resistance by increasing hepatic NKT cells. J Hepatol 2008; 49: 821-30.
137. [137] Ma YY, Li L, Yu CH, Shen Z, Chen LH, Li YM. Effects of probiotics on nonalcoholic fatty liver disease: a meta-analysis. World J Gastroenter 2013; 19: 6911-8.
138. [138] Xiao J, Fai So K, Liong EC, Tipoe GL. Recent advances in the herbal treatment of non-alcoholic Fatty liver disease. J Tradit Complement Med 2013; 3: 88-94.
139. [139] Flora K, Hahn M, Rosen H, Benner K. Milk thistle (Silybum marianum) for the therapy of liver disease. Am J Gastroenterol 1998; 93: 139-43.
140. [140] Abenavoli L. Role of silymarin to treat fibrosis development in non-alcoholic fatty liver disease. Hepatol Res: Official J Japan Soc Hepatol 2011; 41: 668.
141. [141] Cacciapuoti F, Scognamiglio A, Palumbo R, Forte R, Cacciapuoti F. Silymarin in non alcoholic fatty liver disease. World J Hepatol 2013; 5: 109-13.
142. [142] Chavez-Tapia NC, Tellez-Avila FI, Barrientos-Gutierrez T, Mendez-Sanchez N, Lizardi-Cervera J, Uribe M. Bariatric surgery for non-alcoholic steatohepatitis in obese patients. Cochrane Database Syst Rev 2010: CD007340.
143. [143] De Robertis R, D'Onofrio M, Demozzi E, Crosara S, Canestrini S, Pozzi Mucelli R. Noninvasive diagnosis of cirrhosis: A review of different imaging modalities. World J Gastroenterol 2014; 20: 7231-41.
144. [144] Fierbinteanu Braticevici C, Sporea I, Panaitescu E, Tribus L. Value of acoustic radiation force impulse imaging elastography for noninvasive evaluation of patients with nonalcoholic fatty liver disease. Ultrasound Med Biol 2013; 39: 1942-50.