The immunopathogenesis of alcoholic and nonalcoholic steatohepatitis: Two triggers for one disease?

Seminars in Immunopathology

Volumn 31, Issue 3, 2009, Pages 359-369

  Valenti, Luca ^a   Ludovica Fracanzani, Anna ^a   Fargion, Silvia ^a  

^a UNIVERSITY OF MILAN   (Italy)

Author keywords

Cytokine; Inflammation; Insulin resistance; Kupffer cell; Steatosis

Indexed keywords

ACETALDEHYDE; ADIPONECTIN; CORTICOSTEROID; CYTOKINE; EPIDERMAL GROWTH FACTOR RECEPTOR 2; FATTY ACID; GADOLINIUM CHLORIDE; INFLIXIMAB; LEPTIN; LIPOPOLYSACCHARIDE; PENTOXIFYLLINE; PLACEBO; PROBIOTIC AGENT; RESISTIN; TOLL LIKE RECEPTOR 4;

ADAPTIVE IMMUNITY; ALCOHOL CONSUMPTION; ALCOHOLIC FATTY LIVER; CELL ACTIVATION; CELL DAMAGE; CLINICAL TRIAL; CONTROLLED STUDY; CYTOKINE RELEASE; DECOMPENSATED LIVER CIRRHOSIS; DISEASE COURSE; DISEASE DURATION; DRUG EFFECT; FATTY LIVER; FIBROGENESIS; GENE EXPRESSION; HEPATITIS; HEREDITY; HUMAN; IMMUNOPATHOGENESIS; INNATE IMMUNITY; INSULIN RESISTANCE; KUPFFER CELL; LIPID METABOLISM; LIPOGENESIS; LIVER CELL CARCINOMA; METABOLIC DISORDER; NATURAL KILLER CELL; NONALCOHOLIC FATTY LIVER; NONHUMAN; NUTRITIONAL STATUS; OBESITY; PORTAL VEIN BLOOD FLOW; PRIORITY JOURNAL; REVIEW; SEX ROLE; SIGNAL TRANSDUCTION;

ADIPOSE TISSUE; COMPLEMENT ACTIVATION; CYTOKINES; FATTY LIVER; HUMANS; IMMUNE TOLERANCE; INFLAMMATION; KILLER CELLS, NATURAL; KUPFFER CELLS; LIPOPOLYSACCHARIDES; LIVER DISEASES, ALCOHOLIC; SIGNAL TRANSDUCTION; TOLL-LIKE RECEPTOR 4;

EID: 70349570846     PISSN: 18632297     EISSN: 18632300     Source Type: Journal    
DOI: 10.1007/s00281-009-0152-9     Document Type: Review

References (110)

1. Y Adachi BU Bradford W Gao HK Bojes RG Thurman 1994 Inactivation of Kupffer cells prevents early alcohol-induced liver injury Hepatology 20 453
2. LA Adams JF Lymp J St Sauver SO Sanderson KD Lindor A Feldstein P Angulo 2005 The natural history of nonalcoholic fatty liver disease: a population-based cohort study Gastroenterology 129-113
3. E Akriviadis R Botla W Briggs S Han T Reynolds O Shakil 2000 Pentoxifylline improves short-term survival in severe acute alcoholic hepatitis: a double-blind, placebo-controlled trial Gastroenterology 119 1637
4. E Albano E Mottaran M Vidali E Reale S Saksena G Occhino AD Burt CP Day 2005 Immune response towards lipid peroxidation products as a predictor of progression of non-alcoholic fatty liver disease to advanced fibrosis Gut 54 987
5. E Albano 2006 Alcohol, oxidative stress and free radical damage Proc Nutr Soc 65 278
6. R Barbuio M Milanski MB Bertolo MJ Saad LA Velloso 2007 Infliximab reverses steatosis and improves insulin signal transduction in liver of rats fed a high-fat diet J Endocrinol 194-539
7. MT Bardella L Valenti C Pagliari M Peracchi M Fare AL Fracanzani S Fargion 2004 Searching for coeliac disease in patients with non-alcoholic fatty liver disease Dig Liver Dis 36 333-336 (Pubitemid 41115463)
8. AP Bautista 2002 Neutrophilic infiltration in alcoholic hepatitis Alcohol 27 17
9. S Bellentani G Saccoccio F Masutti LS Croce G Brandi F Sasso G Cristanini C Tiribelli 2000 Prevalence of and risk factors for hepatic steatosis in Northern Italy Ann Intern Med 132 112-117
10. GL Bird N Sheron AK Goka GJ Alexander RS Williams 1990 Increased plasma tumor necrosis factor in severe alcoholic hepatitis Ann Intern Med 112 917-920
11. E Bugianesi U Pagotto R Manini E Vanni A Gastaldelli R de Iasio E Gentilcore S Natale M Cassader M Rizzetto R Pasquali G Marchesini 2005 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 90 3498-3504
12. IL Bykov A Vakeva HA Jarvelainen S Meri KO Lindros 2004 Protective function of complement against alcohol-induced rat liver damage Int Immunopharmacol 4 1445
13. D Cai M Yuan DF Frantz PA Melendez L Hansen J Lee SE Shoelson 2005 Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB Nat Med 11 183-190
14. RL Carithers Jr HF Herlong AM Diehl EW Shaw B Combes HJ Fallon WC Maddrey 1989 Methylprednisolone therapy in patients with severe alcoholic hepatitis. A randomized multicenter trial Ann Intern Med 110 685-690
15. X Chen BM Sebastian LE Nagy 2007 Chronic ethanol feeding to rats decreases adiponectin secretion by subcutaneous adipocytes Am J Physiol Endocrinol Metab 292 E621-E628
16. S Chitturi GC Farrell 2007 TNF-alpha as therapeutic target in NASH: tried, but not yet proven J Gastroenterol Hepatol 22 613-614
17. K Cianflone Z Xia LY Chen 2003 Critical review of acylation-stimulating protein physiology in humans and rodents Biochim Biophys Acta 1609-127
18. S Clement C Juge-Aubry A Sgroi S Conzelmann V Pazienza B Pittet-Cuenod CA Meier F Negro 2008 Monocyte chemoattractant protein-1 secreted by adipose tissue induces direct lipid accumulation in hepatocytes Hepatology 48 799
19. M Colombat F Charlotte V Ratziu T Poynard 2002 Portal lymphocytic infiltrate in alcoholic liver disease Hum Pathol 33 1170
20. J Crespo M Rivero E Fabrega A Cayon JA Amado MT Garcia-Unzeta F Pons-Romero 2002 Plasma leptin and TNF-alpha levels in chronic hepatitis C patients and their relationship to hepatic fibrosis Dig Dis Sci 47 1604
21. CP Day 2007 Treatment of alcoholic liver disease Liver Transpl 13 S69
22. G Eberl HR MacDonald 1998 Rapid death and regeneration of NKT cells in anti-CD3epsilon- or IL-12-treated mice: a major role for bone marrow in NKT cell homeostasis Immunity 9 345
23. H Fukui B Brauner JC Bode C Bode 1991 Plasma endotoxin concentrations in patients with alcoholic and non-alcoholic liver disease: reevaluation with an improved chromogenic assay J Hepatol 12 162
24. B Gao WI Jeong Z Tian 2008 Liver: An organ with predominant innate immunity Hepatology 47 729
25. J Grove AK Daly MF Bassendine CP Day 1997 Association of a tumor necrosis factor promoter polymorphism with susceptibility to alcoholic steatohepatitis Hepatology 26 143
26. J Grove AK Daly MF Bassendine E Gilvarry CP Day 2000 Interleukin 10 promoter region polymorphisms and susceptibility to advanced alcoholic liver disease Gut 46 540
27. M Guebre-Xabier S Yang HZ Lin R Schwenk U Krzych AM Diehl 2000 Altered hepatic lymphocyte subpopulations in obesity-related murine fatty livers: potential mechanism for sensitization to liver damage Hepatology 31 633
28. AH Hajeer IV Hutchinson 2001 Influence of TNFalpha gene polymorphisms on TNFalpha production and disease Hum Immunol 62 1191
29. G Haydon PF Lalor SG Hubscher DH Adams 2002 Lymphocyte recruitment to the liver in alcoholic liver disease Alcohol 27 29
30. J Herkel B Jagemann C Wiegard JF Lazaro S Lueth S Kanzler M Blessing E Schmitt AW Lohse 2003 MHC class II-expressing hepatocytes function as antigen-presenting cells and activate specific CD4 T lymphocyutes Hepatology 37 1079
31. DB Hill NB D'Souza EY Lee R Burikhanov IV Deaciuc WJ de Villiers 2002 A role for interleukin-10 in alcohol-induced liver sensitization to bacterial lipopolysaccharide Alcohol Clin Exp Res 26 74 82
32. GS Hotamisligil P Peraldi A Budavari R Ellis MF White BM Spiegelman 1996 IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance Science 271-665
33. GS Hotamisligil 2006 Inflammation and metabolic disorders Nature 444-860
34. I Hritz P Mandrekar A Velayudham D Catalano A Dolganiuc K Kodys E Kurt-Jones G Szabo 2008 The critical role of toll-like receptor (TLR) 4 in alcoholic liver disease is independent of the common TLR adapter MyD88 Hepatology 48 1224
35. HA Jarvelainen A Vakeva KO Lindros S Meri 2002 Activation of complement components and reduced regulator expression in alcohol-induced liver injury in the rat Clin Immunol 105 57
36. Jeong W.I. Park O. Gao B., 2008, Abrogation of the antifibrotic effects of natural killer cells/interferon-gamma contributes to alcohol acceleration of liver fibrosis, Gastroenterology, 134, 248-258
37. H Kanda S Tateya Y Tamori K Kotani K Hiasa R Kitazawa S Kitazawa H Miyachi S Maeda K Egashira M Kasuga 2006 MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity J Clin Invest 116 1494
38. JY Kim E van de Wall M Laplante A Azzara ME Trujillo SM Hofmann T Schraw JL Durand H Li G Li LA Jelicks MF Mehler DY Hui Y Deshaies GI Shulman GJ Schwartz PE Scherer 2007 Obesity-associated improvements in metabolic profile through expansion of adipose tissue J Clin Invest 117 2621
39. H Kono I Rusyn M Yin E Gabele S Yamashina A Dikalova MB Kadiiska HD Connor RP Mason BH Segal BU Bradford SM Holland RG Thurman 2000 NADPH oxidase-derived free radicals are key oxidants in alcohol-induced liver disease J Clin Invest 106-867
40. M Kremer IN Hines RJ Milton MD Wheeler 2006 Favored T helper 1 response in a mouse model of hepatosteatosis is associated with enhanced T cell-mediated hepatitis Hepatology 44 216
41. M Kremer IN Hines 2008 Natural killer T cells and non-alcoholic fatty liver disease: fat chews on the immune system World J Gastroenterol 14 487
42. TK Lam H Yoshii CA Haber E Bogdanovic L Lam IG Fantus A Giacca 2002 Free fatty acid-induced hepatic insulin resistance: a potential role for protein kinase C-delta Am J Physiol Endocrinol Metab 283 E682 E691
43. JY Lee L Zhao HS Youn AR Weatherill R Tapping L Feng WH Lee KA Fitzgerald DH Hwang 2004 Saturated fatty acid activates but polyunsaturated fatty acid inhibits Toll-like receptor 2 dimerized with Toll-like receptor 6 or 1 J Biol Chem 279 16971
44. JY Lee DH Hwang 2006 The modulation of inflammatory gene expression by lipids: mediation through Toll-like receptors Mol Cells 21 174-185
45. Z Li S Yang H Lin J Huang PA Watkins AB Moser C Desimone XY Song AM Diehl 2003 Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease Hepatology 37 343
46. Z Li MJ Soloski AM Diehl 2005 Dietary factors alter hepatic innate immune system in mice with nonalcoholic fatty liver disease Hepatology 42 880-885
47. X Ma J Hua AR Mohamood AR Hamad R Ravi Z Li 2007 A high-fat diet and regulatory T cells influence susceptibility to endotoxin-induced liver injury Hepatology 46 1519
48. X Ma J Hua Z Li 2008 Probiotics improve high fat diet-induced hepatic steatosis and insulin resistance by increasing hepatic NKT cells J Hepatol 49 821
49. JJ Maher P Leon JC Ryan 2008 Beyond insulin resistance: Innate immunity in nonalcoholic steatohepatitis Hepatology 48 670
50. H Malhi SF Bronk NW Werneburg GJ Gores 2006 Free fatty acids induce JNK-dependent hepatocyte lipoapoptosis J Biol Chem 281 12093
51. P Mathurin CL Mendenhall RL Carithers Jr MJ Ramond WC Maddrey P Garstide B Rueff S Naveau JC Chaput T Poynard 2002 Corticosteroids improve short-term survival in patients with severe alcoholic hepatitis (AH): individual data analysis of the last three randomized placebo controlled double blind trials of corticosteroids in severe AH J Hepatol 36 480
52. M Matsumoto D Accili 2005 All roads lead to FoxO Cell Metab 1 215
53. Miele L, Valenza V, La Torre G, Montalto M, Cammarota G, Ricci R, Masciana R, Forgione A, Gabrieli ML, Perotti G, Vecchio FM, Rapaccini G, Gasbarrini G, Day CP, Grieco A (2009) Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease. Hepatology, in press
54. G Musso R Gambino G Biroli M Carello E Faga G Pacini F De Michieli M Cassader M Durazzo M Rizzetto G Pagano 2005 Hypoadiponectinemia predicts the severity of hepatic fibrosis and pancreatic Beta-cell dysfunction in nondiabetic nonobese patients with nonalcoholic steatohepatitis Am J Gastroenterol 100 2438
55. G Musso R Gambino F De Michieli M Durazzo G Pagano M Cassader 2008 Adiponectin gene polymorphisms modulate acute adiponectin response to dietary fat: Possible pathogenetic role in NASH Hepatology 47 1167
56. S Naveau S Chollet-Martin S Dharancy P Mathurin P Jouet MA Piquet T Davion F Oberti P Broet D Emilie 2004 A double-blind randomized controlled trial of infliximab associated with prednisolone in acute alcoholic hepatitis Hepatology 39 1390
57. S Naveau G Perlemuter M Chaillet B Raynard A Balian F Beuzen A Portier P Galanaud D Emilie JC Chaput 2006 Serum leptin in patients with alcoholic liver disease Alcohol Clin Exp Res 30 1422
58. ML Olleros ML Martin D Vesin AL Fotio ML Santiago-Raber L Rubbia-Brandt L Spahr A Hadengue I Garcia 2008 Fat diet and alcohol-induced steatohepatitis after LPS challenge in mice: role of bioactive TNF and Th1 type cytokines Cytokine 44 118
59. U Ozcan Q Cao E Yilmaz AH Lee NN Iwakoshi E Ozdelen G Tuncman C Gorgun LH Glimcher GS Hotamisligil 2004 Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes Science 306-457
60. C Pagano G Soardo C Pilon C Milocco L Basan G Milan D Donnini D Faggian M Mussap M Plebani C Avellini G Federspil LA Sechi R Vettor 2006 Increased serum resistin in nonalcoholic fatty liver disease is related to liver disease severity and not to insulin resistance J Clin Endocrinol Metab 91 1081
61. G Perseghin K Petersen GI Shulman 2003 Cellular mechanism of insulin resistance: potential links with inflammation Int J Obes Relat Metab Disord 27 Suppl 3 S6
62. J Poniachik A Csendes JC Diaz J Rojas P Burdiles F Maluenda G Smok R Rodrigo LA Videla 2006 Increased production of IL-1alpha and TNF-alpha in lipopolysaccharide-stimulated blood from obese patients with non-alcoholic fatty liver disease Cytokine 33 252
63. E Pravdova L Macho N Hlavacova M Fickova 2007 Long-time alcohol intake modifies resistin secretion and expression of resistin gene in adipose tissue Gen Physiol Biophys 26 221-229
64. MT Pritchard MR McMullen AB Stavitsky JI Cohen F Lin ME Medof LE Nagy 2007 Differential contributions of C3, C5, and decay-accelerating factor to ethanol-induced fatty liver in mice Gastroenterology 132 1117
65. Qatanani M, Szwergold NR, Greaves DR, Ahima RS, Lazar MA (2009) Macrophage-derived human resistin exacerbates adipose tissue inflammation and insulin resistance in mice. J Clin Invest, in press
66. Natural killer cells ameliorate liver fibrosis by killing activated stellate cells in NKG2D-dependent and tumor necrosis factor-related apoptosis-inducing ligand-dependent manners, Gastroenterology, 130, 435-452
67. MJ Ramond T Poynard B Rueff P Mathurin C Theodore JC Chaput JP Benhamou 1992 A randomized trial of prednisolone in patients with severe alcoholic hepatitis N Engl J Med 326 507-512
68. Rivera C.A. Adegboyega P. Van Rooijen N.Tagalicud A. Allman M. Wallace M., Toll-like receptor-4 signaling and Kupffer cells play pivotal roles in the pathogenesis of non-alcoholic steatohepatitis
69. CQ Rogers JM Ajmo M You 2008 Adiponectin and alcoholic fatty liver disease IUBMB Life 60 790
70. R Rolla D Vay E Mottaran M Parodi N Traverso S Arico M Sartori G Bellomo LW Klassen GM Thiele DJ Tuma E Albano 2000 Detection of circulating antibodies against malondialdehyde-acetaldehyde adducts in patients with alcohol-induced liver disease Hepatology 31 878
71. S Roychowdhury MR McMullen MT Pritchard AG Hise N van Rooijen ME Medof AB Stavitsky LE Nagy 2009 An early complement-dependent and TLR-4-independent phase in the pathogenesis of ethanol-induced liver injury in mice Hepatology 49 1326
72. A Sahai P Malladi H Melin-Aldana RM Green PF Whitington 2004 Upregulation of osteopontin expression is involved in the development of nonalcoholic steatohepatitis in a dietary murine model Am J Physiol Gastrointest Liver Physiol 287 G264
73. VT Samuel ZX Liu X Qu BD Elder S Bilz D Befroy AJ Romanelli GI Shulman 2004 Mechanism of hepatic insulin resistance in non-alcoholic fatty liver disease J Biol Chem 279 32345
74. VT Samuel ZX Liu A Wang SA Beddow JG Geisler M Kahn XM Zhang BP Monia S Bhanot GI Shulman 2007 Inhibition of protein kinase Cepsilon prevents hepatic insulin resistance in nonalcoholic fatty liver disease J Clin Invest 117-739
75. JM Schattenberg R Singh Y Wang JH Lefkowitch RM Rigoli PE Scherer MJ Czaja 2006 JNK1 but not JNK2 promotes the development of steatohepatitis in mice Hepatology 43 163
76. H Shi MV Kokoeva K Inouye I Tzameli H Yin JS Flier 2006 TLR4 links innate immunity and fatty acid-induced insulin resistance J Clin Invest 116 3015
77. SE Shoelson J Lee AB Goldfine 2006 Inflammation and insulin resistance J Clin Invest 116 1793
78. T Skoog FM van't Hooft B Kallin S Jovinge S Boquist J Nilsson P Eriksson A Hamsten 1999 A common functional polymorphism (C - >A substitution at position -863) in the promoter region of the tumour necrosis factor-alpha (TNF-alpha) gene associated with reduced circulating levels of TNF-alpha Hum Mol Genet 8 1443-1449
79. L Spahr L Rubbia-Brandt JL Frossard E Giostra AL Rougemont J Pugin M Fischer H Egger A Hadengue 2002 Combination of steroids with infliximab or placebo in severe alcoholic hepatitis: a randomized controlled pilot study J Hepatol 37 448
80. R Sreekumar B Rosado D Rasmussen M Charlton 2003 Hepatic gene expression in histologically progressive nonalcoholic steatohepatitis Hepatology 38 244
81. SF Stewart M Vidali CP Day E Albano DE Jones 2004 Oxidative stress as a trigger for cellular immune responses in patients with alcoholic liver disease Hepatology 39 197
82. G Szabo P Mandrekar L Girouard D Catalano 1996 Regulation of human monocyte functions by acute ethanol treatment: decreased tumor necrosis factor-alpha, interleukin-1 beta and elevated interleukin-10, and transforming growth factor-beta production Alcohol Clin Exp Res 20 900
83. H Tamai S Kato Y Horie E Ohki H Yokoyama H Ishii 2000 Effect of acute ethanol administration on the intestinal absorption of endotoxin in rats Alcohol Clin Exp Res 24 390 (Pubitemid 30170220)
84. CM Taniguchi T Kondo M Sajan J Luo R Bronson T Asano R Farese LC Cantley CR Kahn 2006 Divergent regulation of hepatic glucose and lipid metabolism by phosphoinositide 3-kinase via Akt and PKClambda/zeta Cell Metab 3 343
85. V Thakur MT Pritchard MR McMullen LE Nagy 2006 Adiponectin normalizes LPS-stimulated TNF-alpha production by rat Kupffer cells after chronic ethanol feeding Am J Physiol Gastrointest Liver Physiol 290 G998
86. H Tilg AM Diehl 2000 Cytokines in alcoholic and nonalcoholic steatohepatitis N Engl J Med 343 1467
87. H Tilg GS Hotamisligil 2006 Nonalcoholic fatty liver disease: Cytokine-adipokine interplay and regulation of insulin resistance Gastroenterology 131-934
88. K Tokushige M Takakura N Tsuchiya-Matsushita M Taniai E Hashimoto K Shiratori 2007 Influence of TNF gene polymorphisms in Japanese patients with NASH and simple steatosis J Hepatol 46 1104
89. DM Tsukumo MA Carvalho-Filho JB Carvalheira PO Prada SM Hirabara AA Schenka EP Araujo J Vassallo R Curi LA Velloso MJ Saad 2007 Loss-of-function mutation in Toll-like receptor 4 prevents diet-induced obesity and insulin resistance Diabetes 56 1986
90. T Uesugi M Froh GE Arteel BU Bradford RG Thurman 2001 Toll-like receptor 4 is involved in the mechanism of early alcohol-induced liver injury in mice Hepatology 34 101 (Pubitemid 32591488)
91. KT Uysal SM Wiesbrock MW Marino GS Hotamisligil 1997 Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function Nature 389-610
92. L Valenti AL Fracanzani P Dongiovanni G Santorelli A Branchi E Taioli G Fiorelli S Fargion 2002 Tumor necrosis factor alpha promoter polymorphisms and insulin resistance in nonalcoholic fatty liver disease Gastroenterology 122-274
93. L Valenti T De Feo AL Fracanzani E Fatta M Salvagnini S Arico G Rossi G Fiorelli S Fargion 2004 Cytotoxic T-lymphocyte antigen-4 A49G polymorphism is associated with susceptibility to and severity of alcoholic liver disease in Italian patients Alcohol Alcohol 39 276
94. L Valenti R Rametta P Dongiovanni M Maggioni AL Fracanzani M Zappa E Lattuada G Roviaro S Fargion 2008 Increased expression and activity of the transcription factor FOXO1 in nonalcoholic steatohepatitis Diabetes 57 1355
95. D Vay C Rigamonti M Vidali E Mottaran E Alchera G Occhino M Sartori E Albano 2006 Anti-phospholipid antibodies associated with alcoholic liver disease target oxidized phosphatidylserine on apoptotic cell plasma membranes J Hepatol 44 183
96. M Vidali SF Stewart R Rolla AK Daly Y Chen E Mottaran DE Jones JB Leathart CP Day E Albano 2003 Genetic and epigenetic factors in autoimmune reactions toward cytochrome P4502E1 in alcoholic liver disease Hepatology 37 410
97. SP Weisberg D McCann M Desai M Rosenbaum RL Leibel AW Ferrante Jr 2003 Obesity is associated with macrophage accumulation in adipose tissue J Clin Invest 112 1796-1808
98. SP Weisberg D Hunter R Huber J Lemieux S Slaymaker K Vaddi I Charo RL Leibel AW Ferrante Jr 2006 CCR2 modulates inflammatory and metabolic effects of high-fat feeding J Clin Invest 116-115
99. MD Wheeler H Kono M Yin I Rusyn M Froh HD Connor RP Mason RJ Samulski RG Thurman 2001 Delivery of the Cu/Zn-superoxide dismutase gene with adenovirus reduces early alcohol-induced liver injury in rats Gastroenterology 120 1241 (Pubitemid 32248748)
100. MD Wheeler 2003 Endotoxin and Kupffer cell activation in alcoholic liver disease Alcohol Res Health 27 300-306
101. A Wieckowska BG Papouchado Z Li R Lopez NN Zein AE Feldstein 2008 Increased hepatic and circulating interleukin-6 levels in human nonalcoholic steatohepatitis Am J Gastroenterol 103 1372
102. AJ Wigg IC Roberts-Thomson RB Dymock PJ McCarthy RH Grose AG Cummins 2001 The role of small intestinal bacterial overgrowth, intestinal permeability, endotoxaemia, and tumour necrosis factor alpha in the pathogenesis of non-alcoholic steatohepatitis Gut 48 206
103. CJ Willer LL Bonnycastle KN Conneely WL Duren AU Jackson LJ Scott N Narisu PS Chines A Skol HM Stringham J Petrie MR Erdos AJ Swift ST Enloe AG Sprau E Smith M Tong KF Doheny EW Pugh RM Watanabe TA Buchanan TT Valle RN Bergman J Tuomilehto KL Mohlke FS Collins M Boehnke 2007 Screening of 134 single nucleotide polymorphisms (SNPs) previously associated with type 2 diabetes replicates association with 12 SNPs in nine genes Diabetes 56 256
104. CF Xu CH Yu YM Li L Xu J Du Z Shen 2007 Association of the frequency of peripheral natural killer T cells with nonalcoholic fatty liver disease World J Gastroenterol 13 4504-4508
105. T Yamauchi Y Nio T Maki M Kobayashi T Takazawa M Iwabu M Okada-Iwabu S Kawamoto N Kubota T Kubota Y Ito J Kamon A Tsuchida K Kumagai H Kozono Y Hada H Ogata K Tokuyama M Tsunoda T Ide K Murakami M Awazawa I Takamoto P Froguel K Hara K Tobe R Nagai K Ueki T Kadowaki 2007 Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions Nat Med 13 332
106. Z Yesilova M Ozata C Oktenli S Bagci A Ozcan SY Sanisoglu A Uygun H Yaman N Karaeren K Dagalp 2005 Increased acylation stimulating protein concentrations in nonalcoholic fatty liver disease are associated with insulin resistance Am J Gastroenterol 100-842
107. M Yin MD Wheeler H Kono BU Bradford RM Gallucci MI Luster RG Thurman 1999 Essential role of tumor necrosis factor alpha in alcohol-induced liver injury in mice Gastroenterology 117-942
108. M Yin BU Bradford MD Wheeler T Uesugi M Froh SM Goyert RG Thurman 2001 Reduced early alcohol-induced liver injury in CD14-deficient mice J Immunol 166 4737-4742
109. WW Yip AD Burt 2006 Alcoholic liver disease Semin Diagn Pathol 23 149
110. C Zou J Ma X Wang L Guo Z Zhu J Stoops AE Eaker CJ Johnson S Strom GK Michalopoulos MC DeFrances R Zarnegar 2007 Lack of Fas antagonism by Met in human fatty liver disease Nat Med 13 1078