Yamada’s Textbook of Gastroenterology

Sixth Edition

Edited by Daniel K. Podolsky,
Michael Camilleri, J. Gregory Fitz,
Anthony N. Kalloo, Fergus Shanahan, Timothy C. Wang

References

Nonalcoholic fatty liver disease

1. BrowningJD, SzczepaniakLS, DobbinsR, et al.Prevalence of hepatic steatosis in an urban population in the united states: impact of ethnicity. Hepatology2004;40:1387. CrossRef

2. VernonG, BaranovaA, YounossiZM. Systematic review: the epidemiology and natural history of non‐alcoholic fatty liver disease and non‐alcholic steatohepatitis in adults. Hepatology2011;34:274.

3. AdamsLA, LympJF, St SauverJ, et al.The natural history of nonalcoholic fatty liver disease: a population‐based cohort study. Gastroenterology2005;129:113. CrossRef

4. CharltonMR, BurnsJM, PedersenRA, et al.Frequency and outcomes of liver transplantation for nonalcoholic steatohepatitis in the united states. Gastroenterology2011;141:1249. CrossRef

5. LudwigJ, ViggianoTR, McGillDB, et al.Nonalcoholic steatohepatitis: mayo clinic experiences with a hitherto unnamed disease. Mayo Clin Proc1980;55:434.

6. ChalasaniN, YounossiZ, LavineJE, 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. Hepatology2012;55:2005. CrossRef

7. BaconBR, FarahvashMJ, JanneyCG, et al.Nonalcoholic steatohepatitis: an expanded clinical entity. Gastroenterology1994;107:1103.

8. MatteoniCA, YounossiZM, GramlichT, et al.Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology1999;116:1413. CrossRef

9. HamaguchiM, KojimaT, TakedaN, et al.The metabolic syndrome as a predictor of nonalcoholic fatty liver disease. Ann Intern Med2005;143:722. CrossRef

10. ChitturiS, AbeygunasekeraS, FarrellGC, et al.NASH and insulin resistance: insulin hypersecretion and specific association with the insulin resistance syndrome. Hepatology2002;35:373. CrossRef

11. PaganoG, PaciniG, MussoG, et al.Nonalcoholic steatohepatitis, insulin resistance, and metabolic syndrome: further evidence for an etiologic association. Hepatology2002;35:367. CrossRef

12. SuzukiA, AnguloP, LympJ, et al.Chronological development of elevated aminotransferases in a nonalcoholic population. Hepatology2005;41:64. CrossRef

13. WhalleyS, PuvanachandraP, DesaiA, et al.Hepatology outpatient service provision in secondary care: a study of liver disease incidence and resource costs. Clin Med2007;7:119. CrossRef

14. WilliamsCD, StengelJ, AsikeMI, et al.Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle‐aged population utilizing ultrasound and liver biopsy: a prospective study. Gastroenterology2010;140:124. CrossRef

15. LiY, XuC, YuC, et al.Association of serum uric acid level with non‐alcoholic fatty liver disease: a cross‐sectional study. J Hepatol2009;50:1029. CrossRef

16. ZhouYJ, LiYY, NieYQ, et al.Prevalence of fatty liver disease and its risk factors in the population of south china. World J Gastroenterol2007;13:6419. CrossRef

17. LiH, WangYJ, TanK, et al.Prevalence and risk factors of fatty liver disease in chengdu, southwest china. Hepatobiliary Pancreat Dis Int2009;8:377.

18. AlbertiKG, ZimmetP, ShawJ, IDF Epidemiology Task Force Consensus Group. The metabolic syndrome – a new worldwide definition. Lancet2005;366:1059. CrossRef

19. Expert Panel on Detection, Evaluation,and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III). JAMA2001;285:2486. CrossRef

20. FinkelsteinEA, KhavjouOA, ThompsonH, et al.Obesity and severe obesity forecasts through 2030. Am J Prev Med2012;42:563. CrossRef

21. HuffmanMD, CapewellS, NingH, et al.Cardiovascular health behavior and health factor changes (1988‐2008) and projections to 2020: results from the national health and nutrition examination surveys (NHANES). Circulation2012;125:2595. CrossRef

22. HossainP, KawarB, El NahasM. Obesity and diabetes in the developing world–a growing challenge. N Engl J Med2007;356:213. CrossRef

23. MarchesiniG, BugianesiE, ForlaniG, et al.Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology2003;37:917. CrossRef

24. BozaC, RiquelmeA, IbanezL, et al.Predictors of nonalcoholic steatohepatitis (NASH) in obese patients undergoing gastric bypass. Obes Surg2005;15:1148. CrossRef

25. HaentjensP, MassaadD, ReynaertH, et al.Identifying non‐alcoholic fatty liver disease among asymptomatic overweight and obese individuals by clinical and biochemical characteristics. Acta Clin Belg2009;64:483. CrossRef

26. MachadoM, Marques‐VidalP, Cortez‐PintoH. Hepatic histology in obese patients undergoing bariatric surgery. J Hepatol2006;45:600. CrossRef

27. BellentaniS, TiribelliC, SaccoccioG, et al.Prevalence of chronic liver disease in the general population of northern italy: the dionysos study. Hepatology1994;20:1442. CrossRef

28. KotronenA, JuurinenL, HakkarainenA, et al.Liver fat is increased in type 2 diabetic patients and underestimated by serum alanine aminotransferase compared with equally obese nondiabetic subjects. Diabetes Care2008;31:165. CrossRef

29. PrashanthM, GaneshHK, VimaMV, et al.Prevalence of nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus. J Assoc Physicians India2009;57:205.

30. LeiteNC, SallesGF, AraujoALE, et al.Prevalence and associated factors of non‐alcoholic fatty liver disease in patients with type‐2 diabetes mellitus. Liver Int2009;29:113. CrossRef

31. AssyN, KaitaK, MyminD, et al.Fatty infiltration of liver in hyperlipidemic patients. Dig Dis Sci2000;45:1929. CrossRef

32. DiehlAM, GoodmanZ, IshakKG. Alcohol‐like liver disease in nonalcoholics. A clinical and histologic comparison with alcohol‐induced liver injury. Gastroenterology1988;95:1056.

33. DickTJM, LesserIA, LeipsicJA, et al.The effect of obesity on the association between liver fat and carotid atherosclerosis in a multi‐ethnic cohort. Atherosclerosis2013;226:208. CrossRef

34. ChenZW, ChenLY, DaiHL, et al.Relationship between alanine aminotransferase levels and metabolic syndrome in nonalcoholic fatty liver disease. J Zhejiang Univ Sci B2008;9:616. CrossRef

35. KallwitzER, KumarM, AggarwalR, et al.Ethnicity and nonalcoholic fatty liver disease in an obesity clinic: the impact of triglycerides. Dig Dis Sci2008;53:1358. CrossRef

36. OngJP, PittsA, YounossiZM. Increased overall mortality and liver‐related mortality in non‐alcoholic fatty liver disease. J Hepatol2008;49:608. CrossRef

37. PapatheodoridisGV, GoulisJ, ChristodoulouD, et al.High prevalence of elevated liver enzymes in blood donors: associations with male gender and central adiposity. Eur J Gastroenterol Hepatol2007;19:281. CrossRef

38. ClarkJM, BrancatiFL, DiehlAM. The prevalence and etiology of elevated aminotransferase levels in the united states. Am J Gastroenterol2003;98:960. CrossRef

39. FischerGE, BialekSP, HomanCE, et al.Chronic liver disease among Alaska‐Native people, 2003‐2004. Am J Gastroenterol2009;104:363. CrossRef

40. BialekSR, ReddJT, LynchA, et al.Chronic liver disease among two American Indian patient populations in the southwestern United States, 2000‐2003. J Clin Gastroenterol2008;42:849. CrossRef

41. AmarapurkarD, KamaniP, PatelN, et al.Prevalence of non‐alcoholic fatty liver disease: population based study. Ann Hepatol2007;6:161.

42. AschaMS, HanounehIA, LopezR, et al.The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. Hepatology2010;51:1972. CrossRef

43. SchwimmerJB, CeledonMA, LavineJE, et al.Heritability of nonalcoholic fatty liver disease. Gastroenterology2009;136:1585. CrossRef

44. SpeliotesEK, Yerges‐ArmstrongLM, WuJ, et al.Genome‐wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits. PLoS Genet2011;7:e1001324. CrossRef

45. RomeoS, KozlitinaJ, XingC, et al.Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet2008;40:1461. CrossRef

46. MieleL, BealeG, PatmanG, et al.The kruppel‐like factor 6 genotype is associated with fibrosis in nonalcoholic fatty liver disease. Gastroenterology2008;135:282. CrossRef

47. EkstedtM, FranzenLE, MathiesenUL, et al.Long‐term follow‐up of patients with NAFLD and elevated liver enzymes. Hepatology2006;44:865. CrossRef

48. KleinerDE, BruntEM, Van NattaM, et al.Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology2005;41:1313. CrossRef

49. ChalasaniN, WilsonL, KleinerDE, et al.Relationship of steatosis grade and zonal location to histological features of steatohepatitis in adult patients with non‐alcoholic fatty liver disease. J Hepatol2008;48:829. CrossRef

50. JepsenP, VilstrupH, MellemkjaerL, et al.Prognosis of patients with a diagnosis of fatty liver–a registry‐based cohort study. Hepatogastroenterology2003;50:2101.

51. Dam‐LarsenS, BeckerU, FranzmannM, et al.Final results of a long‐term, clinical follow‐up in fatty liver patients. Scand J Gastroenterol2009;44:1236. CrossRef

52. MussoG, GambinoR, CassaderM, et al.Meta‐analysis: natural history of non‐alcoholic fatty liver disease (NAFLD) and diagnostic accuracy of non‐invasive tests for liver disease severity. Ann Med2011;43:617. CrossRef

53. AnguloP, KeachJC, BattsKP, et al.Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology1999;30:1356. CrossRef

54. OmaryMB, KuN, StrnadP, et al.Toward unraveling the complexity of simple epithelial keratins in human disease. J Clin Invest2009;119:1794. CrossRef

55. BruntEM, JanneyCG, Di BisceglieAM, et al.Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol1999;94:2467. CrossRef

56. BruntEM, KleinerDE, WilsonLA, et al.Nonalcoholic fatty liver disease (NAFLD) activity score and the histopathologic diagnosis in NAFLD: distinct clinicopathologic meanings. Hepatology2011;53:810. CrossRef

57. YounossiZM, StepanovaM, RafiqN, et al.Pathologic criteria for nonalcoholic steatohepatitis: interprotocol agreement and ability to predict liver‐related mortality. Hepatology2011;53:1874. CrossRef

58. DayCP, JamesOF. Steatohepatitis: a tale of two “hits”?Gastroenterology1998;114:842. CrossRef

59. KumashiroN, ErionDM, ZhangD, et al.Cellular mechanism of insulin resistance in nonalcoholic fatty liver disease. Proc Natl Acad Sci U S A2011;108:16381. CrossRef

60. FracanzaniAL, ValentiL, BugianesiE, et al.Risk of severe liver disease in nonalcoholic fatty liver disease with normal aminotransferase levels: a role for insulin resistance and diabetes. Hepatology2008;48:792. CrossRef

61. SanyalAJ, Campbell‐SargentC, MirshahiF, et al.Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. Gastroenterology2001;120:1183. CrossRef

62. MarchesiniG, BriziM, Morselli‐LabateAM, et al.Association of nonalcoholic fatty liver disease with insulin resistance. Am J Med1999;107:450. CrossRef

63. ChawlaA, NguyenKD, GohYP. Macrophage‐mediated inflammation in metabolic disease. Nat Rev Immunol2011;11:738. CrossRef

64. LolmedeK, Durand de Saint FrontV, GalitzkyJ, et al.Effects of hypoxia on the expression of proangiogenic factors in differentiated 3T3‐F442A adipocytes. Int J Obes Relat Metab Disord2003;27:1187. CrossRef

65. WeisbergSP, McCannD, DesaiM, et al.Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest2003;112:1796. CrossRef

66. XuH, BarnesGT, YangQ, et al.Chronic inflammation in fat plays a crucial role in the development of obesity‐related insulin resistance. J Clin Invest2003;112:1821. CrossRef

67. LinJ, YangR, TarrPT, et al.Hyperlipidemic effects of dietary saturated fats mediated through PGC‐1beta coactivation of SREBP. Cell2005;120:261. CrossRef

68. HardieDG. Minireview: the AMP‐activated protein kinase cascade: the key sensor of cellular energy status. Endocrinology2003;144:5179. CrossRef

69. KawaguchiT, OsatomiK, YamashitaH, et al.Mechanism for fatty acid “sparing” effect on glucose‐induced transcription: regulation of carbohydrate‐responsive element‐binding protein by AMP‐activated protein kinase. J Biol Chem2002;277:3829. CrossRef

70. ShimomuraI, BashmakovY, IkemotoS, et al.Insulin selectively increases SREBP‐1c mRNA in the livers of rats with streptozotocin‐induced diabetes. Proc Natl Acad Sci U S A1999;96:13656. CrossRef

71. IshiiS, IizukaK, MillerBC, et al.Carbohydrate response element binding protein directly promotes lipogenic enzyme gene transcription. Proc Natl Acad Sci U S A2004;101:15597. CrossRef

72. VosMB, LavineJE. Dietary fructose in nonalcoholic fatty liver disease. Hepatology2013;57:2524.

73. ChenG, LiangG, OuJ, et al.Central role for liver X receptor in insulin‐mediated activation of srebp‐1c transcription and stimulation of fatty acid synthesis in liver. Proc Natl Acad Sci U S A2004;101:11245. CrossRef

74. ChaJY, RepaJJ. The liver X receptor (LXR) and hepatic lipogenesis. the carbohydrate‐response element‐binding protein is a target gene of LXR. J Biol Chem2007;282:743. CrossRef

75. MaL, RobinsonLN, TowleHC. ChREBP*Mlx is the principal mediator of glucose‐induced gene expression in the liver. J Biol Chem2006;281:28721. CrossRef

76. DonnellyKL, SmithCI, SchwarzenbergSJ, et al.Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest2005;115:1343. CrossRef

77. LomonacoR, Ortiz‐LopezC, OrsakB, et al.Effect of adipose tissue insulin resistance on metabolic parameters and liver histology in obese patients with nonalcoholic fatty liver disease. Hepatology2012;55:1389. CrossRef

78. WolfrumC, StoffelM. Coactivation of Foxa2 through pgc‐1beta promotes liver fatty acid oxidation and triglyceride/VLDL secretion. Cell Metab2006;3:99. CrossRef

79. SatoR, MiyamotoW, InoueJ, et al.Sterol regulatory element‐binding protein negatively regulates microsomal triglyceride transfer protein gene transcription. J Biol Chem1999;274:24714. CrossRef

80. LefebvreP, ChinettiG, FruchartJC, et al.Sorting out the roles of PPAR alpha in energy metabolism and vascular homeostasis. J Clin Invest2006;116:571. CrossRef

81. StienstraR, MandardS, PatsourisD, et al.Peroxisome proliferator‐activated receptor alpha protects against obesity‐induced hepatic inflammation. Endocrinology2007;148:2753. CrossRef

82. Fernández‐MirandaC, Pérez‐CarrerasM, ColinaF, et al.A pilot trial of fenofibrate for the treatment of non‐alcoholic fatty liver disease. Dig Liver Dis2008;40:200. CrossRef

83. FievetC, StaelsB. Efficacy of peroxisome proliferator‐activated receptor agonists in diabetes and coronary artery disease. Curr Atheroscler Rep2009;11:281. CrossRef

84. FraynKN. Adipose tissue as a buffer for daily lipid flux. Diabetologia2002;45:1201. CrossRef

85. MaedaN, TakahashiM, FunahashiT, et al.PPARgamma ligands increase expression and plasma concentrations of adiponectin, an adipose‐derived protein. Diabetes2001;50:2094. CrossRef

86. YamauchiT, KamonJ, ItoY, et al.Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature2003;423:762. CrossRef

87. OuchiN, KiharaS, AritaY, et al.Adiponectin, an adipocyte‐derived plasma protein, inhibits endothelial NF‐kappaB signaling through a cAMP‐dependent pathway. Circulation2000;102:1296. CrossRef

88. MarraF, EfsenE, RomanelliRG, et al.Ligands of peroxisome proliferator‐activated receptor gamma modulate profibrogenic and proinflammatory actions in hepatic stellate cells. Gastroenterology2000;119:466. CrossRef

89. YavromS, ChenL, XiongS, et al.Peroxisome proliferator‐activated receptor gamma suppresses proximal alpha1(I) collagen promoter via inhibition of p300‐facilitated NF‐I binding to DNA in hepatic stellate cells. J Biol Chem2005;280:40650. CrossRef

90. SamuelVT, LiuZX, QuX, et al.Mechanism of hepatic insulin resistance in non‐alcoholic fatty liver disease. J Biol Chem2004;279:32345. CrossRef

91. DayCP. Pathogenesis of steatohepatitis. Best Pract Res Clin Gastroenterol2002;16:663. CrossRef

92. LeeCH, OlsonP, EvansRM. Minireview: lipid metabolism, metabolic diseases, and peroxisome proliferator‐activated receptors. Endocrinology2003;144:2201. CrossRef

93. RobertsonG, LeclercqI, FarrellGC. Nonalcoholic steatosis and steatohepatitis. II. cytochrome P‐450 enzymes and oxidative stress. Am J Physiol Gastrointest Liver Physiol2001;281:G1135.

94. TilgH, DiehlAM. Cytokines in alcoholic and nonalcoholic steatohepatitis. N Engl J Med2000;343:1467. CrossRef

95. ServiddioG, BellantiF, TamborraR, et al.Uncoupling protein‐2 (UCP2) induces mitochondrial proton leak and increases susceptibility of non‐alcoholic steatohepatitis (NASH) liver to ischaemia‐reperfusion injury. Gut2008;57:957. CrossRef

96. Cortez‐PintoH, ChathamJ, ChackoVP, et al.Alterations in liver ATP homeostasis in human nonalcoholic steatohepatitis: a pilot study. JAMA1999;282:1659. CrossRef

97. FulopP, DerdakZ, SheetsA, et al.Lack of UCP2 reduces fas‐mediated liver injury in ob/ob mice and reveals importance of cell‐specific UCP2 expression. Hepatology2006;44:592. CrossRef

98. MariM, CaballeroF, ColellA, et al.Mitochondrial free cholesterol loading sensitizes to TNF‐ and fas‐mediated steatohepatitis. Cell Metab2006;4:185. CrossRef

99. De CraemerD, PauwelsM, Van den BrandenC. Alterations of peroxisomes in steatosis of the human liver: a quantitative study. Hepatology1995;22:744. CrossRef

100. CharltonM, AnguloP, ChalasaniN, et al.Low circulating levels of dehydroepiandrosterone in histologically advanced nonalcoholic fatty liver disease. Hepatology2008;47:484. CrossRef

101. MatsuzawaN, TakamuraT, KuritaS, et al.Lipid‐induced oxidative stress causes steatohepatitis in mice fed an atherogenic diet. Hepatology2007;46:1392. CrossRef

102. NobiliV, PastoreA, GaetaLM, et al.Glutathione metabolism and antioxidant enzymes in patients affected by nonalcoholic steatohepatitis. Clin Chim Acta2005;355:105. CrossRef

103. VidelaLA, RodrigoR, ArayaJ, et al.Oxidative stress and depletion of hepatic long‐chain polyunsaturated fatty acids may contribute to nonalcoholic fatty liver disease. Free Radic Biol Med2004;37:1499. CrossRef

104. ChalasaniN, DeegMA, CrabbDW. Systemic levels of lipid peroxidation and its metabolic and dietary correlates in patients with nonalcoholic steatohepatitis. Am J Gastroenterol2004;99:1497. CrossRef

105. LoguercioC, De GirolamoV, de SioI, et al.Non‐alcoholic fatty liver disease in an area of southern Italy: main clinical, histological, and pathophysiological aspects. J Hepatol2001;35:568. CrossRef

106. YamaguchiK, YangL, McCallS, et al.Inhibiting triglyceride synthesis improves hepatic steatosis but exacerbates liver damage and fibrosis in obese mice with nonalcoholic steatohepatitis. Hepatology2007;45:1366. CrossRef

107. NolanCJ, LarterCZ. Lipotoxicity: why do saturated fatty acids cause and monounsaturates protect against it?J Gastroenterol Hepatol2009;24:703. CrossRef

108. LiZZ, BerkM, McIntyreTM, et al.Hepatic lipid partitioning and liver damage in nonalcoholic fatty liver disease: role of stearoyl‐CoA desaturase. J Biol Chem2008;284:5637.

109. BechmannLP, GieselerRK, SowaJP, et al.Apoptosis is associated with CD36/fatty acid translocase upregulation in non‐alcoholic steatohepatitis. Liver Int2010;●0:850.

110. Baskin‐BeyES, GoresGJ. Death by association: BH3 domain‐only proteins and liver injury. Am J Physiol Gastrointest Liver Physiol2005;289:G987. CrossRef

111. FeldsteinAE, CanbayA, AnguloP, et al.Hepatocyte apoptosis and fas expression are prominent features of human nonalcoholic steatohepatitis. Gastroenterology2003;125:437. CrossRef

112. FeldsteinAE, CanbayA, GuicciardiME, et al.Diet associated hepatic steatosis sensitizes to fas mediated liver injury in mice. J Hepatol2003;39:978. CrossRef

113. FeldsteinAE, WerneburgNW, CanbayA, et al.Free fatty acids promote hepatic lipotoxicity by stimulating TNF‐alpha expression via a lysosomal pathway. Hepatology2004;40:185. CrossRef

114. MalhiH, BronkSF, WerneburgNW, et al.Free fatty acids induce JNK‐dependent hepatocyte lipoapoptosis. J Biol Chem2006;281:12093. CrossRef

115. BarreyroFJ, KobayashiS, BronkSF, et al.Transcriptional regulation of bim by FoxO3A mediates hepatocyte lipoapoptosis. J Biol Chem2007;282:27141. CrossRef

116. Baskin‐BeyES, CanbayA, BronkSF, et al.Cathepsin B inactivation attenuates hepatocyte apoptosis and liver damage in steatotic livers after cold ischemia‐warm reperfusion injury. Am J Physiol Gastrointest Liver Physiol2005;288:G396. CrossRef

117. BoyaP, AndreauK, PoncetD, et al.Lysosomal membrane permeabilization induces cell death in a mitochondrion‐dependent fashion. J Exp Med2003;197:1323. CrossRef

118. MalhiH, BarreyroFJ, IsomotoH, et al.Free fatty acids sensitise hepatocytes to TRAIL mediated cytotoxicity. Gut2007;56:1124. CrossRef

119. RibeiroPS, Cortez‐PintoH, SolaS, et al.Hepatocyte apoptosis, expression of death receptors, and activation of NF‐kappaB in the liver of nonalcoholic and alcoholic steatohepatitis patients. Am J Gastroenterol2004;99:1708. CrossRef

120. LeyRE, PetersonDA, GordonJI. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell2006;124:837. CrossRef

121. WellsJM, RossiO, MeijerinkM, et al.Epithelial crosstalk at the microbiota‐mucosal interface [immunology]. Proc Natl Acad Sci U S A2010;108:4607. CrossRef

122. CaniPD, PossemiersS, Van de WieleT, et al.Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP‐2‐driven improvement of gut permeability. Gut2009;58:1091. CrossRef

123. DelzenneNM, CaniPD. Interaction between obesity and the gut microbiota: relevance in nutrition. Annu Rev Nutr2010;31:15. CrossRef

124. PoupeauA, PosticC. Cross‐regulation of hepatic glucose metabolism via ChREBP and nuclear receptors. Biochim Biophys Acta2011;1812:995. CrossRef

125. DingS, ChiMM, ScullBP, et al.High‐fat diet: bacteria interactions promote intestinal inflammation which precedes and correlates with obesity and insulin resistance in mouse. PLoS ONE2010;5:e12191. CrossRef

126. BackhedF, DingH, WangT, et al.The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A2004;101:15718. CrossRef

127. MieleL, ValenzaV, La TorreG, et al.Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease. Hepatology2009;49:1877. CrossRef

128. GhoshalS, WittaJ, ZhongJ, et al.Chylomicrons promote intestinal absorption of lipopolysaccharides. J Lipid Res2008;50:90. CrossRef

129. RiveraCA, AdegboyegaP, van RooijenN, et al.Toll‐like receptor‐4 signaling and kupffer cells play pivotal roles in the pathogenesis of non‐alcoholic steatohepatitis. J Hepatol2007;47:571. CrossRef

130. FriedmanSL. Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver. Physiol Rev2008;88:125. CrossRef

131. JiangJX, VenugopalS, SerizawaN, et al.Reduced nicotinamide adenine dinucleotide phosphate oxidase 2 plays a key role in stellate cell activation and liver fibrogenesis in vivo. Gastroenterology2010;139:1375. CrossRef

132. SekiE, De MinicisS, OsterreicherCH, et al.TLR4 enhances TGF‐beta signaling and hepatic fibrosis. Nat Med2007;13:1324. CrossRef

133. SynWK, ChoiSS, LiaskouE, et al.Osteopontin is induced by hedgehog pathway activation and promotes fibrosis progression in nonalcoholic steatohepatitis. Hepatology2010;53:106. CrossRef

134. MancoM, MarcelliniM, GiannoneG, et al.Correlation of serum TNF‐alpha levels and histologic liver injury scores in pediatric nonalcoholic fatty liver disease. Am J Clin Pathol2007;127:954. CrossRef

135. Cortez‐PintoH, BaptistaA, CamiloME, et al.Hepatic stellate cell activation occurs in nonalcoholic steatohepatitis. Hepatogastroenterology2001;48:87.

136. KamadaY, TamuraS, KisoS, et al.Enhanced carbon tetrachloride‐induced liver fibrosis in mice lacking adiponectin. Gastroenterology2003;125:1796. CrossRef

137. Teixeira‐ClercF, JulienB, GrenardP, et al.CB1 cannabinoid receptor antagonism: a new strategy for the treatment of liver fibrosis. Nat Med2006;12:671. CrossRef

138. ParadisV, PerlemuterG, BonvoustF, et al.High glucose and hyperinsulinemia stimulate connective tissue growth factor expression: a potential mechanism involved in progression to fibrosis in nonalcoholic steatohepatitis. Hepatology2001;34:738. CrossRef

139. SöderbergC, StålP, AsklingJ, et al.Decreased survival of subjects with elevated liver function tests during a 28‐year follow‐up. Hepatology2009;51:595. CrossRef

140. TargherG, BertoliniL, PadovaniR, et al.Relations between carotid artery wall thickness and liver histology in subjects with nonalcoholic fatty liver disease. Diabetes Care2006;29:1325. CrossRef

141. TargherG, BertoliniL, PadovaniR, et al.Prevalence of nonalcoholic fatty liver disease and its association with cardiovascular disease among type 2 diabetic patients. Diabetes Care2007;30:1212. CrossRef

142. SookoianS, PirolaCJ. Non‐alcoholic fatty liver disease is strongly associated with carotid atherosclerosis: a systematic review. J Hepatol2008;49:600. CrossRef

143. JemalA, BrayF, CenterMM, et al.Global cancer statistics [articles]. CA Cancer J Clin2011;61:69. CrossRef

144. FattovichG, StroffoliniT, ZagniI, et al.Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology2004;127(5 Suppl 1):S35. CrossRef

145. LokAS, SeeffLB, MorganTR, et al.Incidence of hepatocellular carcinoma and associated risk factors in hepatitis C‐related advanced liver disease. Gastroenterology2009;136:138. CrossRef

146. LarssonSC, WolkA. Overweight, obesity and risk of liver cancer: a meta‐analysis of cohort studies. Br J Cancer2007;97:1005.

147. El‐SeragHB, HampelH, JavadiF. The association between diabetes and hepatocellular carcinoma: a systematic review of epidemiologic evidence. Clin Gastroenterol Hepatol2006;4:369. CrossRef

148. YasuiK, HashimotoE, KomorizonoY, et al.Characteristics of patients with nonalcoholic steatohepatitis who develop hepatocellular carcinoma. Clin Gastroenterol Hepatol2011;9:428; quiz e50. CrossRef

149. StraubBK, HerpelE, SingerS, et al.Lipid droplet‐associated PAT‐proteins show frequent and differential expression in neoplastic steatogenesis. Mod Pathol2010;23:480. CrossRef

150. YamashitaT, HondaM, TakatoriH, et al.Activation of lipogenic pathway correlates with cell proliferation and poor prognosis in hepatocellular carcinoma. J Hepatol2009;50:100. CrossRef

151. VinciguerraM, CarrozzinoF, PeyrouM, et al.Unsaturated fatty acids promote hepatoma proliferation and progression through downregulation of the tumor suppressor PTEN. J Hepatol2009;50:1132. CrossRef

152. GaidosJKJ, HillnerBE, SanyalAJ. A decision analysis study of the value of a liver biopsy in nonalcoholic steatohepatitis. Liver Int2008;28:650. CrossRef

153. BedogniG, BellentaniS, MiglioliL, et al.The fatty liver index: a simple and accurate predictor of hepatic steatosis in the general population. BMC Gastroenterol2006;6:33. CrossRef

154. KotronenA, PeltonenM, HakkarainenA, et al.Prediction of non‐alcoholic fatty liver disease and liver fat using metabolic and genetic factors. Gastroenterology2009;137:865. CrossRef

155. PoynardT, RatziuV, NaveauS, et al.The diagnostic value of biomarkers (SteatoTest) for the prediction of liver steatosis. Comp Hepatol2005;4:10. CrossRef

156. BedogniG, KahnHS, BellentaniS, et al.A simple index of lipid overaccumulation is a good marker of liver steatosis. BMC Gastroenterol2010;10:98. CrossRef

157. RyanCK, JohnsonLA, GerminBI, et al.One hundred consecutive hepatic biopsies in the workup of living donors for right lobe liver transplantation. Liver Transpl2002;8:1114. CrossRef

158. MottinCC, MorettoM, PadoinAV, et al.The role of ultrasound in the diagnosis of hepatic steatosis in morbidly obese patients. Obes Surg2004;14:635. CrossRef

159. ReederSB, CruiteI, HamiltonG, et al.Quantitative assessment of liver fat with magnetic resonance imaging and spectroscopy. J Magn Reson Imaging2011;34:4. CrossRef

160. SaadehS, YounossiZM, RemerEM, et al.The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology2002;123:745. CrossRef

161. CapristoE, MieleL, ForgioneA, et al.Nutritional aspects in patients with non‐alcoholic steatohepatitis (NASH). Eur Rev Med Pharmacol Sci2005;9:265.

162. CentisE, MoscatielloS, BugianesiE, et al.Stage of change and motivation to healthier lifestyle in non‐alcoholic fatty liver disease. J Hepatol2012;58:771. CrossRef

163. TuomilehtoJ, LindstromJ, ErikssonJG, et al.Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med2001;344:1343. CrossRef

164. SessoHD, PaffenbargerRSJr, LeeIM. Physical activity and coronary heart disease in men: the harvard alumni health study. Circulation2000;102:975. CrossRef

165. WeiM, KampertJB, BarlowCE, et al.Relationship between low cardiorespiratory fitness and mortality in normal‐weight, overweight, and obese men. JAMA1999;282:1547. CrossRef

166. MussoG, GambinoR, De MichieliF, et al.Dietary habits and their relations to insulin resistance and postprandial lipemia in nonalcoholic steatohepatitis. Hepatology2003;37:909. CrossRef

167. KangH, GreensonJK, OmoJT, et al.Metabolic syndrome is associated with greater histologic severity, higher carbohydrate, and lower fat diet in patients with NAFLD. Am J Gastroenterol2006;101:2247. CrossRef

168. HuangMA, GreensonJK, ChaoC, et al.One‐year intense nutritional counseling results in histological improvement in patients with non‐alcoholic steatohepatitis: a pilot study. Am J Gastroenterol2005;100:1072. CrossRef

169. PromratK, KleinerDE, NiemeierHM, et al.Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology2010;51:121. CrossRef

170. Perez‐GuisadoJ, Munoz‐SerranoA. The effect of the Spanish ketogenic Mediterranean diet on nonalcoholic fatty liver disease: a pilot study. J Med Food2011;14:667.

171. SacksFM, BrayGA, CareyVJ, et al.Comparison of weight‐loss diets with different compositions of fat, protein, and carbohydrates. N Engl J Med2009;360:859. CrossRef

172. Executive summary. Executive summary of the clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults. Arch Intern Med1998;158:1855. CrossRef

173. Sreenivasa BabaC, AlexanderG, KalyaniB, et al.Effect of exercise and dietary modification on serum aminotransferase levels in patients with nonalcoholic steatohepatitis. J Gastroenterol Hepatol2006;21:191. CrossRef

174. JohnsonNA, SachinwallaT, WaltonDW, et al.Aerobic exercise training reduces hepatic and visceral lipids in obese individuals without weight loss. Hepatology2009;50:1105. CrossRef

175. MusiN, GoodyearLJ. Insulin resistance and improvements in signal transduction. Endocrine2006;29:73. CrossRef

176. MarchesiniG, BriziM, BianchiG, et al.Metformin in non‐alcoholic steatohepatitis. Lancet2001;358:893. CrossRef

177. BugianesiE, GentilcoreE, ManiniR, et al.A randomized controlled trial of metformin versus vitamin E or prescriptive diet in nonalcoholic fatty liver disease. Am J Gastroenterol2005;100:1082. CrossRef

178. UygunA, KadayifciA, IsikAT, et al.Metformin in the treatment of patients with non‐alcoholic steatohepatitis. Aliment Pharmacol Ther2004;19:537. CrossRef

179. de OliveiraCPMS, StefanoJT, de SiqueiraERF, et al.Combination of N‐acetylcysteine and metformin improves histological steatosis and fibrosis in patients with non‐alcoholic steatohepatitis. Hepatol Res2007;38:159.

180. DusejaA, DasA, DhimanRK, et al.Metformin is effective in achieving biochemical response in patients with nonalcoholic fatty liver disease (NAFLD) not responding to lifestyle interventions. Ann Hepatol2007;6:222.

181. IdilmanR, MizrakD, CorapciogluD, et al.Clinical trial: insulin‐sensitizing agents may reduce consequences of insulin resistance in individuals with non‐alcoholic steatohepatitis. Aliment Pharmacol Ther2008;28:200. CrossRef

182. NairS, DiehlAM, WisemanM, et al.Metformin in the treatment of non‐alcoholic steatohepatitis: a pilot open label trial. Aliment Pharmacol Ther2004;20:23. CrossRef

183. HaukelandJW, KonopskiZ, EggesboHB, et al.Metformin in patients with non‐alcoholic fatty liver disease: a randomized, controlled trial. Scand J Gastroenterol2009;44:853. CrossRef

184. LoombaR, LutchmanG, KleinerDE, et al.Clinical trial: pilot study of metformin for the treatment of non‐alcoholic steatohepatitis. Aliment Pharmacol Ther2009;29:172. CrossRef

185. MussoG, GambinoR, CassaderM, et al.A meta‐analysis of randomized trials for the treatment of nonalcoholic fatty liver disease. Hepatology2010;52:79. CrossRef

186. LavineJE, SchwimmerJB, Van NattaML, et al.Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial [original contribution]. JAMA2011;305:1659. CrossRef

187. Neuschwander‐TetriBA, BruntEM, WehmeierKR, et al.Improved nonalcoholic steatohepatitis after 48 weeks of treatment with the PPAR‐gamma ligand rosiglitazone. Hepatology2003;38:1008. CrossRef

188. SanyalAJ, MofradPS, ContosMJ, et al.A pilot study of vitamin E versus vitamin E and pioglitazone for the treatment of nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol2004;2:1107. CrossRef

189. PromratK, LutchmanG, UwaifoGI, et al.A pilot study of pioglitazone treatment for nonalcoholic steatohepatitis. Hepatology2004;39:188. CrossRef

190. BelfortR, HarrisonSA, BrownK, et al.A placebo‐controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med2006;355:2297. CrossRef

191. AithalGP, ThomasJA, KayePV, et al.Randomized, placebo‐controlled trial of pioglitazone in nondiabetic subjects with nonalcoholic steatohepatitis. Gastroenterology2008;135:1176. CrossRef

192. RatziuV, GiralP, JacqueminetS, et al.Rosiglitazone for nonalcoholic steatohepatitis: one‐year results of the randomized placebo‐controlled fatty liver improvement with rosiglitazone therapy (FLIRT) trial. Gastroenterology2008;135:100. CrossRef

193. RatziuV, CharlotteF, BernhardtC, et al.Long‐term efficacy of rosiglitazone in nonalcoholic steatohepatitis: results of the fatty liver improvement by rosiglitazone therapy (FLIRT 2) extension trial. Hepatology2010;51:445. CrossRef

194. SanyalAJ, ChalasaniN, KowdleyKV, et al.Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med2010;362:1675. CrossRef

195. NissenSE, WolskiK. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med2007;356:2457. CrossRef

196. HomePD, PocockSJ, Beck‐NielsenH, et al.Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open‐label trial. Lancet2009;373:2125. CrossRef

197. DormandyJA, CharbonnelB, EcklandDJ, et al.Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive study (PROspective pioglitAzone clinical trial in macroVascular events): a randomised controlled trial. Lancet2005;366:1279. CrossRef

198. MeierC, KraenzlinME, BodmerM, et al.Use of thiazolidinediones and fracture risk. Arch Intern Med2008;168:820. CrossRef

199. LandrierJF, GourantonE, El YazidiC, et al.Adiponectin expression is induced by vitamin E via a peroxisome proliferator‐activated receptor gamma‐dependent mechanism. Endocrinology2009;150:5318. CrossRef

200. CankurtaranM, KavT, YavuzB, et al.Serum vitamin‐E levels and its relation to clinical features in nonalcoholic fatty liver disease with elevated ALT levels. Acta Gastroenterol Belg2006;69:5.

201. HarrisonSA, TorgersonS, HayashiP, et al.Vitamin E and vitamin C treatment improves fibrosis in patients with nonalcoholic steatohepatitis. Am J Gastroenterol2003;98:2485. CrossRef

202. LindorKD, KowdleyKV, HeathcoteEJ, et al.Ursodeoxycholic acid for treatment of nonalcoholic steatohepatitis: results of a randomized trial. Hepatology2004;39:770. CrossRef

203. NelsonA, TorresDM, MorganAE, et al.A pilot study using simvastatin in the treatment of nonalcoholic steatohepatitis: a randomized placebo‐controlled trial. J Clin Gastroenterol2009;43:990. CrossRef

204. AthyrosVG, TziomalosK, GossiosTD, et al.Safety and efficacy of long‐term statin treatment for cardiovascular events in patients with coronary heart disease and abnormal liver tests in the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) study: a post‐hoc analysis. Lancet2010;376:1916. CrossRef

205. BasaranogluM, AcbayO, SonsuzA. A controlled trial of gemfibrozil in the treatment of patients with nonalcoholic steatohepatitis. J Hepatol1999;31:384. CrossRef

206. MeratS, MalekzadehR, SohrabiMR, et al.Probucol in the treatment of non‐alcoholic steatohepatitis: a double‐blind randomized controlled study. J Hepatol2003;38:414. CrossRef

207. HalstedCH, VillanuevaJA, DevlinAM. Folate deficiency, methionine metabolism, and alcoholic liver disease. Alcohol2002;27:169. CrossRef

208. AbdelmalekMF, SandersonSO, AnguloP, et al.Betaine for nonalcoholic fatty liver disease: results of a randomized placebo‐controlled trial. Hepatology2009;50:1818. CrossRef

209. ClarkJM, AlkhuraishiAR, SolgaSF, et al.Roux‐en‐Y gastric bypass improves liver histology in patients with non‐alcoholic fatty liver disease. Obes Res2005;13:1180. CrossRef

210. BarkerKB, PalekarNA, BowersSP, et al.Non‐alcoholic steatohepatitis: effect of roux‐en‐Y gastric bypass surgery. Am J Gastroenterol2006;101:368. CrossRef

211. WeinerRA. Surgical treatment of non‐alcoholic steatohepatitis and non‐alcoholic fatty liver disease. Dig Dis2010;28:274. CrossRef

212. MathurinP, HollebecqueA, ArnalsteenL, et al.Prospective study of the long‐term effects of bariatric surgery on liver injury in patients without advanced disease. Gastroenterology2009;137:532. CrossRef

213. DonnellyKL, SmithCL, SchwarzenbergSJ, et al.Sources of fatty acid stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest2005;115:1343. CrossRef