Non-alcoholic fatty liver disease

References

• Angulo P. Nonalcoholic fatty liver disease. N Engl J Med 2002;346:1221–1231.
   PubMed Web of Science ®Google Scholar
• Rafiq N, Bai C, Fang Y, Srishord M, McCullough A, Gramlich T, Younossi ZM Long-term follow-up of patients with nonalcoholic fatty liver. Clin Gastroenterol Hepatol 2009;7:234–238.
   PubMed Web of Science ®Google Scholar
• Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract 2010;87:4–14.
   PubMed Web of Science ®Google Scholar
• Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, Cohen JC, Grundy SM, Hobbs HH Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 2004;40:1387–1395.
   PubMed Web of Science ®Google Scholar
• Zelber-Sagi S, Nitzan-Kaluski D, Halpern Z, Oren R. Prevalence of primary non-alcoholic fatty liver disease in a population-based study and its association with biochemical and anthropometric measures. Liver Int 2006;26:856–863.
   PubMed Web of Science ®Google Scholar
• Fan JG, Zhu J, Li XJ, Chen L, Li L, Dai F, Li F, Chen SY. Prevalence of and risk factors for fatty liver in a general population of Shanghai, China. J Hepatol 2005;43:508–514.
   PubMed Web of Science ®Google Scholar
• Shen L, Fan JG, Shao Y, Zeng MD, Wang JR, Luo GH, Li JQ, Chen SY. Prevalence of nonalcoholic fatty liver among administrative officers in Shanghai: an epidemiological survey. World J Gastroenterol 2003;9:1106–1110.
   PubMed Web of Science ®Google Scholar
• Das K, Mukherjee PS, Ghosh A, Ghosh S, Mridha AR, Dhibar T, Bhattacharya B, Bhattacharya B, Manna B, Dhali GK, Santra A, Chowdury A. Nonobese population in a developing country has a high prevalence of nonalcoholic fatty liver and significant liver disease. Hepatology 2010;51:1593–1602.
   PubMed Web of Science ®Google Scholar
• Schwimmer JB, Deutsch R, Kahen T, Lavine JE, Stanley C, Behling C. Prevalence of fatty liver in children and adolescents. Pediatrics 2006;118:1388–1393.
   PubMed Web of Science ®Google Scholar
• Molleston JP, White F, Teckman J, Fitzgerald JF. Obese children with steatohepatitis can develop cirrhosis in childhood. Am J Gastroenterol 2002;97:2460–2462.
   PubMed Web of Science ®Google Scholar
• Patton HM, Lavine JE, Van Natta ML, Schwimmer JB, Kleiner D, Molleston J. Clinical correlates of histopathology in pediatric nonalcoholic steatohepatitis. Gastroenterology 2008;135:1961–1971 e2.
   PubMed Web of Science ®Google Scholar
• Nomura H, Kashiwagi S, Hayashi J, Kajiyama W, Tani S, Goto M. Prevalence of fatty liver in a general population of Okinawa, Japan. Jpn J Med. 1988 May;27(2):142–9.
   Google Scholar
• Kagansky N, Levy S, Keter D, Rimon E, Taiba Z, Fridman Z, Berger D, Knobler H, Malnick S. Non-alcoholic fatty liver disease–a common and benign finding in octogenarian patients. Liver Int 2004;24:588–594.
   PubMed Web of Science ®Google Scholar
• Hamaguchi M, Kojima T, Takeda N, Nakagawa T, Taniguchi H, Fujii K, Omatsu T, Nakajima T, Sarui H, Shimazaki M, Kato T, Okuda J, Ida K. The metabolic syndrome as a predictor of nonalcoholic fatty liver disease. Ann Intern Med 2005;143:722–728.
   PubMed Web of Science ®Google Scholar
• Malik SM, deVera ME, Fontes P, Shaikh O, Ahmad J. Outcome after liver transplantation for NASH cirrhosis. Am J Transplant 2009;9:782–793.
   PubMed Web of Science ®Google Scholar
• Bellentani S, Saccoccio G, Masutti F, Croce LS, Brandi G, Sasso F, Cristanini G, Tiribelli C. Prevalence of and risk factors for hepatic steatosis in Northern Italy. Ann Intern Med 2000; 132:112–117.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Guerrero R, Vega GL, Grundy SM, Browning JD. Ethnic differences in hepatic steatosis: an insulin resistance paradox? Hepatology 2009;49:791–801.
   PubMed Web of Science ®Google Scholar
• Jimba S, Nakagami T, Takahashi M, Wakamatsu T, Hirota Y, Iwamoto Y, Wasada T. Prevalence of non-alcoholic fatty liver disease and its association with impaired glucose metabolism in Japanese adults. Diabet Med 2005;22:1141–1145.
   PubMed Web of Science ®Google Scholar
• Kim HJ, Lee KE, Kim DJ, Kim SK, Ahn CW, Lim SK, Kim KR, Lee HC, Huh KB, Cha BS. Metabolic significance of nonalcoholic fatty liver disease in nonobese, nondiabetic adults. Arch Intern Med 2004;164:2169–2175.
   PubMedGoogle Scholar
• Nadalin S, Malago M, Valentin-Gamazo C, Testa G, Baba HA, Liu C, Fruhauf NR, Schaffer R, Gerken G, Frilling A, Broelsch CE. Preoperative donor liver biopsy for adult living donor liver transplantation: risks and benefits. Liver Transpl 2005;11:980–986.
   PubMed Web of Science ®Google Scholar
• Minervini MI, Ruppert K, Fontes P, Volpes R, Vizzini G, de Vera ME, Gruttadauria S, Miraglia R, Pipitone L, Marsh JW, Marcos A, Gridelli B, Demetris AJ. Liver biopsy findings from healthy potential living liver donors: reasons for disqualification, silent diseases and correlation with liver injury tests. J Hepatol 2009;50:501–510.
   PubMed Web of Science ®Google Scholar
• Wanless IR, Lentz JS. Fatty liver hepatitis (steatohepatitis) and obesity: an autopsy study with analysis of risk factors. Hepatology 1990;12:1106–1110.
   PubMed Web of Science ®Google Scholar
• Williams CD, Stengel J, Asike MI, Torres DM, Shaw J, Contreras M, Landt CL, Harrison SA. Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study. Gastroenterology 2011;140:124–131.
   PubMed Web of Science ®Google Scholar
• Mathurin P, Hollebecque A, Arnalsteen L, Buob D, Leteurtre E, Caiazzo R, Pigeyre M, Verkindt H, Dharancy S, Louvet A, Romon M, Pattou F. Prospective study of the long-term effects of bariatric surgery on liver injury in patients without advanced disease. Gastroenterology 2009;137:532–540.
   PubMed Web of Science ®Google Scholar
• Kallwitz ER, Guzman G, TenCate V, Vitello J, Layden-Almer J, Berkes J, Patel R, Layden TJ, Cotler SJ. The histologic spectrum of liver disease in African-American, non-Hispanic white, and Hispanic obesity surgery patients. Am J Gastroenterol 2009;104:64–69.
   PubMed Web of Science ®Google Scholar
• Day CP, James OF. Steatohepatitis: a tale of two “hits”? Gastroenterology 1998;114:842–845.
   PubMed Web of Science ®Google Scholar
• Tilg H, Moschen AR. Evolution of inflammation in nonalcoholic fatty liver disease: the multiple parallel hits hypothesis. Hepatology 2010;52:1836–1846.
   PubMed Web of Science ®Google Scholar
• Adams LA, Angulo P, Lindor KD. Nonalcoholic fatty liver disease. CMAJ 2005;172:899–905.
   PubMed Web of Science ®Google Scholar
• Browning JD, Horton JD. Molecular mediators of hepatic steatosis and liver injury. J Clin Invest 2004;114:147–152.
   PubMed Web of Science ®Google Scholar
• Charlton M, Sreekumar R, Rasmussen D, Lindor K, Nair KS. Apolipoprotein synthesis in nonalcoholic steatohepatitis. Hepatology 2002;35:898–904.
   PubMed Web of Science ®Google Scholar
• Tetri LH, Basaranoglu M, Brunt EM, Yerian LM, Neuschwander-Tetri BA. Severe NAFLD with hepatic necroinflammatory changes in mice fed trans fats and a high-fructose corn syrup equivalent. Am J Physiol Gastrointest Liver Physiol 2008;295:G987–995.
   PubMed Web of Science ®Google Scholar
• Abdelmalek MF, Suzuki A, Guy C, Unalp-Arida A, Colvin R, Johnson RJ, Diehl AM. Increased fructose consumption is associated with fibrosis severity in patients with nonalcoholic fatty liver disease. Hepatology 2010;51:1961–1971.
   PubMed Web of Science ®Google Scholar
• Stanhope KL, Schwarz JM, Keim NL, Griffen SC, Bremer AA, Graham JL, Hatcher B, Cox CL, Dyachenko A, Zhang W, McGahan JP, Seibert A, Krauss RM, Chiu S, Schaefer EJ, Ai M, Otokozawa S, Nakajima K, Nakano T, Beysen C, Hellerstein MK, Berglund L, Havel PJ. Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans. J Clin Invest 2009;119:1322–1334.
   PubMed Web of Science ®Google Scholar
• Neuschwander-Tetri BA. Hepatic lipotoxicity and the pathogenesis of nonalcoholic steatohepatitis: the central role of nontriglyceride fatty acid metabolites. Hepatology 2010;52:774–788.
   PubMed Web of Science ®Google Scholar
• Alkhouri N, Dixon LJ, Feldstein AE. Lipotoxicity in nonalcoholic fatty liver disease: not all lipids are created equal. Expert Rev Gastroenterol Hepatol 2009;3:445–451.
   PubMedGoogle Scholar
• Koliwad SK, Streeper RS, Monetti M, Cornelissen I, Chan L, Terayama K, Naylor S, Rao M, Hubbard B, Farese RV Jr. DGAT1-dependent triacylglycerol storage by macrophages protects mice from diet-induced insulin resistance and inflammation. J Clin Invest 2010;120:756–767.
   PubMed Web of Science ®Google Scholar
• Monetti M, Levin MC, Watt MJ, Sajan MP, Marmor S, Hubbard BK, Stevens RD, Bain JR, Newgard CB, Farese RV, Sr. Hevener, AL, Farese RV Jr. Dissociation of hepatic steatosis and insulin resistance in mice overexpressing DGAT in the liver. Cell Metab 2007;6:69–78.
   PubMed Web of Science ®Google Scholar
• Unger RH, Scherer PE. Gluttony, sloth and the metabolic syndrome: a roadmap to lipotoxicity. Trends Endocrinol Metab 2010;21:345–352.
   PubMed Web of Science ®Google Scholar
• Li ZZ, Berk M, McIntyre TM, Feldstein AE. Hepatic lipid partitioning and liver damage in nonalcoholic fatty liver disease: role of stearoyl-CoA desaturase. J Biol Chem 2009;284:5637–5644.
   PubMed Web of Science ®Google Scholar
• Feldstein AE, Canbay A, Guicciardi ME, Higuchi H, Bronk SF, Gores GJ. Diet associated hepatic steatosis sensitizes to Fas mediated liver injury in mice. J Hepatol 2003;39:978–983.
   PubMed Web of Science ®Google Scholar
• Malhi H, Barreyro FJ, Isomoto H, Bronk SF, Gores GJ. Free fatty acids sensitise hepatocytes to TRAIL mediated cytotoxicity. Gut 2007;56:1124–1131.
   PubMed Web of Science ®Google Scholar
• Malhi H, Bronk SF, Werneburg NW, Gores GJ. Free fatty acids induce JNK-dependent hepatocyte lipoapoptosis. J Biol Chem 2006;281:12093–12101.
   PubMed Web of Science ®Google Scholar
• Bouchier-Hayes L, Lartigue L, Newmeyer DD. Mitochondria: pharmacological manipulation of cell death. J Clin Invest 2005;115:2640–2647.
   PubMed Web of Science ®Google Scholar
• Caldwell SH, Chang CY, Nakamoto RK, Krugner-Higby L. Mitochondria in nonalcoholic fatty liver disease. Clin Liver Dis 2004;8:595–617.
   PubMedGoogle Scholar
• Sanyal AJ, Campbell-Sargent C, Mirshahi F, Rizzo WB, Contos MJ, Sterling RK, Luketic VA, Shiffman ML, Clore JN. Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. Gastroenterology 2001;120:1183–1192.
   PubMed Web of Science ®Google Scholar
• Cortez-Pinto H, Chatham J, Chacko VP, Arnold C, Rashid A, Diehl AM. Alterations in liver ATP homeostasis in human nonalcoholic steatohepatitis: a pilot study. JAMA 1999;282:1659–1664.
   PubMed Web of Science ®Google Scholar
• Feldstein AE, Werneburg NW, Canbay A, Guicciardi ME, Bronk SF, Rydzewski R, Burgart LJ, Gores GJ. Free fatty acids promote hepatic lipotoxicity by stimulating TNF-alpha expression via a lysosomal pathway. Hepatology 2004;40:185–194.
   PubMed Web of Science ®Google Scholar
• Feng B, Yao PM, Li Y, Devlin CM, Zhang D, Harding HP, Sweeney M, Rong JX, Kuriakose G, Fisher EA, Marks AR, Ron D, Tabas I. The endoplasmic reticulum is the site of cholesterol-induced cytotoxicity in macrophages. Nat Cell Biol 2003;5:781–792.
   PubMed Web of Science ®Google Scholar
• Wei Y, Wang D, Topczewski F, Pagliassotti MJ. Saturated fatty acids induce endoplasmic reticulum stress and apoptosis independently of ceramide in liver cells. Am J Physiol Endocrinol Metab 2006;291:E275–281.
   PubMed Web of Science ®Google Scholar
• Todd DJ, Lee AH, Glimcher LH. The endoplasmic reticulum stress response in immunity and autoimmunity. Nat Rev Immunol 2008;8:663–674.
   PubMed Web of Science ®Google Scholar
• Puri P, Wiest MM, Cheung O, Mirshahi F, Sargeant C, Min HK, Contos MJ, Sterling RK, Fuchs M, Zhou H, Watkins SM, Sanyal AJ. The plasma lipidomic signature of nonalcoholic steatohepatitis. Hepatology 2009;50:1827–1838.
   PubMed Web of Science ®Google Scholar
• Kapoor A, Sanyal AJ. Endoplasmic reticulum stress and the unfolded protein response. Clin Liver Dis 2009;13:581–590.
   PubMed Web of Science ®Google Scholar
• Yoshida H. Unconventional splicing of XBP-1 mRNA in the unfolded protein response. Antioxid Redox Signal 2007;9:2323–2333.
   PubMed Web of Science ®Google Scholar
• Hotamisligil GS. Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell 2010;140:900–917.
   PubMed Web of Science ®Google Scholar
• Yang L, Li P, Fu S, Calay ES, Hotamisligil GS. Defective hepatic autophagy in obesity promotes ER stress and causes insulin resistance. Cell Metab 2010;11:467–478.
   PubMed Web of Science ®Google Scholar
• Singh R, Kaushik S, Wang Y, Xiang Y, Novak I, Komatsu M, Tanaka K, Cuervo AM, Czaja MJ. Autophagy regulates lipid metabolism. Nature 2009;458:1131–1135.
   PubMed Web of Science ®Google Scholar
• Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 2003;112:1796–1808.
   PubMed Web of Science ®Google Scholar
• Wellen KE, Hotamisligil GS. Inflammation, stress, and diabetes. J Clin Invest 2005;115:1111–1119.
   PubMed Web of Science ®Google Scholar
• Hotamisligil GS. Inflammation and metabolic disorders. Nature 2006;444:860–867.
   PubMed Web of Science ®Google Scholar
• Marchesini G, Brizi M, Morselli-Labate AM, Bianchi G, Bugianesi E, McCullough AJ, Forlani G, Melchionda N. Association of nonalcoholic fatty liver disease with insulin resistance. Am J Med 1999;107:450–455.
   PubMed Web of Science ®Google Scholar
• Marchesini G, Bugianesi E, Forlani G, Cerrelli F, Lenzi M, Manini R, Natale S, Vanni E, Villanova N, Melchionda N, Rizzetto M. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology 2003;37:917–923.
   PubMed Web of Science ®Google Scholar
• Banerji MA, Buckley MC, Chaiken RL, Gordon D, Lebovitz HE, Kral JG. Liver fat, serum triglycerides and visceral adipose tissue in insulin-sensitive and insulin-resistant black men with NIDDM. Int J Obes Relat Metab Disord 1995;19:846–850.
   PubMed Web of Science ®Google Scholar
• 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:E906–916.
   PubMed Web of Science ®Google Scholar
• Toledo FG, Sniderman AD, Kelley DE. Influence of hepatic steatosis (fatty liver) on severity and composition of dyslipidemia in type 2 diabetes. Diabetes Care 2006;29:1845–1850.
   PubMed Web of Science ®Google Scholar
• van der Poorten D, Milner KL, Hui J, Hodge A, Trenell MI, Kench JG, London R, Peduto T, Chisholm DJ, George J. Visceral fat: a key mediator of steatohepatitis in metabolic liver disease. Hepatology 2008;48:449–457.
   PubMed Web of Science ®Google Scholar
• Ibrahim MM. Subcutaneous and visceral adipose tissue: structural and functional differences. Obes Rev 2010;11:11–18.
   PubMed Web of Science ®Google Scholar
• Haque M, Sanyal AJ. The metabolic abnormalities associated with non-alcoholic fatty liver disease. Best Pract Res Clin Gastroenterol 2002;16:709–731.
   PubMed Web of Science ®Google Scholar
• Jaeschke A, Davis RJ. Metabolic stress signaling mediated by mixed-lineage kinases. Mol Cell 2007;27:498–508.
   PubMed Web of Science ®Google Scholar
• Aguirre V, Uchida T, Yenush L, Davis R, White MF. The c-Jun NH(2)-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of Ser(307). J Biol Chem 2000;275:9047–9054.
   PubMed Web of Science ®Google Scholar
• Weston CR, Davis RJ. The JNK signal transduction pathway. Curr Opin Cell Biol 2007;19:142–149.
   PubMed Web of Science ®Google Scholar
• Sabio G, Das M, Mora A, Zhang Z, Jun JY, Ko HJ, Barrett T, Kim JK, Davis RJ. A stress signaling pathway in adipose tissue regulates hepatic insulin resistance. Science 2008;322:1539–1543.
   PubMed Web of Science ®Google Scholar
• Solinas G, Vilcu C, Neels JG, Bandyopadhyay GK, Luo JL, Naugler W, Grivennikov S, Wynshaw-Boris A, Scadeng M, Olefsky JM, Karin M. JNK1 in hematopoietically derived cells contributes to diet-induced inflammation and insulin resistance without affecting obesity. Cell Metab 2007;6:386–397.
   PubMed Web of Science ®Google Scholar
• Hirosumi J, Tuncman G, Chang L, Gorgun CZ, Uysal KT, Maeda K, Karin M, Hotamisligil GS. A central role for JNK in obesity and insulin resistance. Nature 2002;420:333–336.
   PubMed Web of Science ®Google Scholar
• Schattenberg JM, Wang Y, Singh R, Rigoli RM, Czaja MJ. Hepatocyte CYP2E1 overexpression and steatohepatitis lead to impaired hepatic insulin signaling. J Biol Chem 2005;280:9887–9894.
   PubMed Web of Science ®Google Scholar
• 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;103:1372–1379.
   PubMed Web of Science ®Google Scholar
• Senn JJ, Klover PJ, Nowak IA, Zimmers TA, Koniaris LG, Furlanetto RW, Mooney RA. Suppressor of cytokine signaling-3 (SOCS-3), a potential mediator of interleukin-6-dependent insulin resistance in hepatocytes. J Biol Chem 2003;278:13740–13746.
   PubMed Web of Science ®Google Scholar
• Cai D, Yuan M, Frantz DF, Melendez PA, Hansen L, Lee J, Shoelson SE. Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB. Nat Med 2005;11:183–190.
   PubMed Web of Science ®Google Scholar
• Paradis V, Perlemuter G, Bonvoust F, Dargere D, Parfait B, Vidaud M, Conti M, Huet S, Ba N, Buffet C, Bedossa P. High glucose and hyperinsulinemia stimulate connective tissue growth factor expression: a potential mechanism involved in progression to fibrosis in nonalcoholic steatohepatitis. Hepatology 2001;34:738–744.
   PubMed Web of Science ®Google Scholar
• Sugimoto R, Enjoji M, Kohjima M, Tsuruta S, Fukushima M, Iwao M, Sonta T, Kotoh K, Inoguchi T, Nakamuta M. High glucose stimulates hepatic stellate cells to proliferate and to produce collagen through free radical production and activation of mitogen-activated protein kinase. Liver Int 2005;25:1018–1026.
   PubMed Web of Science ®Google Scholar
• Kern PA, Saghizadeh M, Ong JM, Bosch RJ, Deem R, Simsolo RB. The expression of tumor necrosis factor in human adipose tissue. Regulation by obesity, weight loss, and relationship to lipoprotein lipase. J Clin Invest 1995;95:2111–2119.
   PubMed Web of Science ®Google Scholar
• Diehl AM. Tumor necrosis factor and its potential role in insulin resistance and nonalcoholic fatty liver disease. Clin Liver Dis 2004;8:619–638.
   PubMedGoogle Scholar
• Crespo J, Cayon A, Fernandez-Gil P, Hernandez-Guerra M, Mayorga M, Dominguez-Diez A, Fernandez-Escalante JC, Pons-Romero F. Gene expression of tumor necrosis factor alpha and TNF-receptors, p55 and p75, in nonalcoholic steatohepatitis patients. Hepatology 2001;34:1158–1163.
   PubMed Web of Science ®Google Scholar
• Kantartzis K, Rittig K, Balletshofer B, Machann J, Schick F, Porubska K, Fritsche A, Haring HU, Stefan N. The relationships of plasma adiponectin with a favorable lipid profile, decreased inflammation, and less ectopic fat accumulation depend on adiposity. Clin Chem 2006;52:1934–1942.
   PubMed Web of Science ®Google Scholar
• Hui JM, Hodge A, Farrell GC, Kench JG, Kriketos A, George J. Beyond insulin resistance in NASH: TNF-alpha or adiponectin? Hepatology 2004;40:46–54.
   PubMed Web of Science ®Google Scholar
• Kaser S, Moschen A, Cayon A, Kaser A, Crespo J, Pons-Romero F, Ebenbichler CF, Patsch JR, Tilg H. Adiponectin and its receptors in non-alcoholic steatohepatitis. Gut 2005;54:117–121.
   PubMed Web of Science ®Google Scholar
• Xu A, Wang Y, Keshaw H, Xu LY, Lam KS, Cooper GJ. The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice. J Clin Invest 2003;112:91–100.
   PubMed Web of Science ®Google Scholar
• Kadowaki T, Yamauchi T, Kubota N, Hara K, Ueki K, Tobe K. Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest 2006;116:1784–1792.
   PubMed Web of Science ®Google Scholar
• Procaccini C, Galgani M, De Rosa V, Carbone F, La Rocca C, Ranucci G, Iorio R, Matarese G. Leptin: the prototypic adipocytokine and its role in NAFLD. Curr Pharm Des 2010;16:1902–1912.
   PubMed Web of Science ®Google Scholar
• Leclercq IA, Farrell GC, Schriemer R, Robertson GR. Leptin is essential for the hepatic fibrogenic response to chronic liver injury. J Hepatol 2002; 37:206–213.
   PubMed Web of Science ®Google Scholar
• Anania FA. Leptin, liver, and obese mice–fibrosis in the fat lane. Hepatology 2002;36:246–248.
   PubMed Web of Science ®Google Scholar
• Angulo P, Alba LM, Petrovic LM, Adams LA, Lindor KD, Jensen MD. Leptin, insulin resistance, and liver fibrosis in human nonalcoholic fatty liver disease. J Hepatol 2004;41:943–949.
   PubMed Web of Science ®Google Scholar
• Struben VM, Hespenheide EE, Caldwell SH. Nonalcoholic steatohepatitis and cryptogenic cirrhosis within kindreds. Am J Med 2000;108:9–13.
   PubMed Web of Science ®Google Scholar
• Mohanty SR, Troy TN, Huo D, O’Brien BL, Jensen DM, Hart J. Influence of ethnicity on histological differences in non-alcoholic fatty liver disease. J Hepatol 2009;50:797–804.
   PubMed Web of Science ®Google Scholar
• Riquelme A, Arrese M, Soza A, Morales A, Baudrand R, Perez-Ayuso RM, Gonzalez R, Alvarez M, Hernandez V, Garcia-Zattera MJ, Otarola F, Medina B, Rigotti A, Miquel JF, Marshall G, Nervi F. Non-alcoholic fatty liver disease and its association with obesity, insulin resistance and increased serum levels of C-reactive protein in Hispanics. Liver Int 2009;29:82–88.
   PubMed Web of Science ®Google Scholar
• Weston SR, Leyden W, Murphy R, Bass NM, Bell BP, Manos MM, Terrault NA. Racial and ethnic distribution of nonalcoholic fatty liver in persons with newly diagnosed chronic liver disease. Hepatology 2005;41:372–379.
   PubMed Web of Science ®Google Scholar
• Hooper AJ, Adams LA, Burnett JR. Genetic determinants of hepatic steatosis in man. J Lipid Res 2011;52:593–617.
   PubMed Web of Science ®Google Scholar
• Romeo S, Huang-Doran I, Baroni MG, Kotronen A. Unravelling the pathogenesis of fatty liver disease: patatin-like phospholipase domain-containing 3 protein. Curr Opin Lipidol 2010;21:247–252.
   PubMed Web of Science ®Google Scholar
• Romeo S, Kozlitina J, Xing C, Pertsemlidis A, Cox D, Pennacchio LA, Boerwinkle E, Cohen JC, Hobbs HH. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet 2008;40:1461–1465.
   PubMed Web of Science ®Google Scholar
• Valenti L, Al-Serri A, Daly AK, Galmozzi E, Rametta R, Dongiovanni P, Nobili V, Mozzi E, Roviaro G, Vanni E, Bugianesi E, Maggioni M, Fracanzani AL, Fargion S, Day CP. Homozygosity for the patatin-like phospholipase-3/adiponutrin I148M polymorphism influences liver fibrosis in patients with nonalcoholic fatty liver disease. Hepatology 2010;51:1209–1217.
   PubMed Web of Science ®Google Scholar
• He S, McPhaul C, Li JZ, Garuti R, Kinch L, Grishin NV, Cohen JC, Hobbs HH. A sequence variation (I148M) in PNPLA3 associated with nonalcoholic fatty liver disease disrupts triglyceride hydrolysis. J Biol Chem 2010;285:6706–6715.
   PubMed Web of Science ®Google Scholar
• Petersen KF, Dufour S, Hariri A, Nelson-Williams C, Foo JN, Zhang XM, Dziura J, Lifton RP, Shulman GI. Apolipoprotein C3 gene variants in nonalcoholic fatty liver disease. N Engl J Med 2010;362:1082–1089.
   PubMed Web of Science ®Google Scholar
• Loria P, Adinolfi LE, Bellentani S, Bugianesi E, Grieco A, Fargion S, Gasbarrini A, Loguercio C, Lonardo A, Marchesini G, Marra F, Persico M, Prati D, Baroni GS. Practice guidelines for the diagnosis and management of nonalcoholic fatty liver disease. A decalogue from the Italian Association for the Study of the Liver (AISF) Expert Committee. Dig Liver Dis 2010;42:272–282.
   PubMedGoogle Scholar
• Harrison SA, Neuschwander-Tetri BA. Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Clin Liver Dis 2004;8:861–879.
   PubMedGoogle Scholar
• 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;42:132–138.
   PubMed Web of Science ®Google Scholar
• Torres DM, Harrison SA. Diagnosis and therapy of nonalcoholic steatohepatitis. Gastroenterology 2008134:1682–1698.
   Google Scholar
• Prati D, Taioli E, Zanella A, Della Torre E, Butelli S, Del Vecchio E, Vianello L, Zanuso F, Mozzi F, Milani S, Conte D, Colombo M, Sirchia G. Updated definitions of healthy ranges for serum alanine aminotransferase levels. Ann Intern Med 2002;137:1–10.
   PubMed Web of Science ®Google Scholar
• 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;42:650–656.
   PubMed Web of Science ®Google Scholar
• Milner KL, van der Poorten D, Xu A, Bugianesi E, Kench JG, Lam KS, Chisholm DJ, George J. Adipocyte fatty acid binding protein levels relate to inflammation and fibrosis in nonalcoholic fatty liver disease. Hepatology 2009;49:1926–1934.
   PubMed Web of Science ®Google Scholar
• Machado M, Marques-Vidal P, Cortez-Pinto H. Hepatic histology in obese patients undergoing bariatric surgery. J Hepatol 2006;45:600–606.
   PubMed Web of Science ®Google Scholar
• Aithal GP, Thomas JA, Kaye PV, Lawson A, Ryder SD, Spendlove I, Austin AS, Freeman JG, Morgan L, Webber J. Randomized, placebo-controlled trial of pioglitazone in nondiabetic subjects with nonalcoholic steatohepatitis. Gastroenterology 2008;135:1176–1184.
   PubMed Web of Science ®Google Scholar
• Harrison SA, Oliver D, Arnold HL, Gogia S, Neuschwander-Tetri BA. Development and validation of a simple NAFLD clinical scoring system for identifying patients without advanced disease. Gut 2008;57:1441–1447.
   PubMed Web of Science ®Google Scholar
• Fracanzani AL, Valenti L, Bugianesi E, Andreoletti M, Colli A, Vanni E, Bertelli C, Fatta E, Bignamini D, Marchesini G, Fargion S. Risk of severe liver disease in nonalcoholic fatty liver disease with normal aminotransferase levels: a role for insulin resistance and diabetes. Hepatology 2008;48:792–798.
   PubMed Web of Science ®Google Scholar
• Sorrentino P, Tarantino G, Conca P, Perrella A, Terracciano M, Vecchione R, Gargiulo G, Gennarelli N, Lobello R. Silent nonalcoholic fatty liver disease-a clinical-histological study. J Hepatol 2004;41:751–757.
   PubMed Web of Science ®Google Scholar
• Mofrad P, Contos MJ, Haque M, Sargeant C, Fisher RA, Luketic VA, Sterling RK, Shiffman ML, Stravitz RT, Sanyal AJ. Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values. Hepatology 2003;37:1286–1292.
   PubMed Web of Science ®Google Scholar
• Feldstein AE, Wieckowska A, Lopez AR, Liu YC, Zein NN, McCullough AJ. Cytokeratin-18 fragment levels as noninvasive biomarkers for nonalcoholic steatohepatitis: a multicenter validation study. Hepatology 2009;50:1072–1078.
   PubMed Web of Science ®Google Scholar
• Kayadibi H, Gultepe M, Yasar B, Ince AT, Ozcan O, Ipcioglu OM, Kurdas OO, Bolat B, Benek YZ, Guveli H, Atalay S, Ozkara S, Keskin O. Diagnostic value of serum prolidase enzyme activity to predict the liver histological lesions in non-alcoholic fatty liver disease: a surrogate marker to distinguish steatohepatitis from simple steatosis. Dig Dis Sci 2009;54:1764–1771.
   PubMed Web of Science ®Google Scholar
• Angulo P, Keach JC, Batts KP, Lindor KD. Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology 1999;30:1356–1362.
   PubMed Web of Science ®Google Scholar
• McPherson S, Stewart SF, Henderson E, Burt AD, Day CP. Simple non-invasive fibrosis scoring systems can reliably exclude advanced fibrosis in patients with non-alcoholic fatty liver disease. Gut 2010;59:1265–1269.
   PubMed Web of Science ®Google Scholar
• Chitturi S, Weltman M, Farrell GC, McDonald D, Kench J, Liddle C, Samarasinghe D, Lin R, Abeygunasekera S, George J. HFE mutations, hepatic iron, and fibrosis: ethnic-specific association of NASH with C282Y but not with fibrotic severity. Hepatology 2002;36:142–149.
   PubMed Web of Science ®Google Scholar
• Bugianesi E, Manzini P, D’Antico S, Vanni E, Longo F, Leone N, Massarenti P, Piga A, Marchesini G, Rizzetto M. Relative contribution of iron burden, HFE mutations, and insulin resistance to fibrosis in nonalcoholic fatty liver. Hepatology 2004;39:179–187.
   PubMed Web of Science ®Google Scholar
• Valenti L, Fracanzani AL, Bugianesi E, Dongiovanni P, Galmozzi E, Vanni E, Canavesi E, Lattuada E, Roviaro G, Marchesini G, Fargion S. HFE genotype, parenchymal iron accumulation, and liver fibrosis in patients with nonalcoholic fatty liver disease. Gastroenterology 2010;138:905–912.
   PubMed Web of Science ®Google Scholar
• Bedogni G, Miglioli L, Masutti F, Tiribelli C, Marchesini G, Bellentani S. Prevalence of and risk factors for nonalcoholic fatty liver disease: the Dionysos nutrition and liver study. Hepatology 2005;42:44–52.
   PubMed Web of Science ®Google Scholar
• Saadeh S, Younossi ZM, Remer EM, Gramlich T, Ong JP, Hurley M, Mullen KD, Cooper JN, Sheridan MJ. The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology 2002;123:745–750.
   PubMed Web of Science ®Google Scholar
• Palmentieri B, de Sio I, La Mura V, Masarone M, Vecchione R, Bruno S, Torella R, Persico M. The role of bright liver echo pattern on ultrasound B-mode examination in the diagnosis of liver steatosis. Dig Liver Dis 2006;38:485–489.
   PubMedGoogle Scholar
• Hamaguchi M, Kojima T, Itoh Y, Harano Y, Fujii K, Nakajima T, Kato T, Takeda N, Okuda J, Ida K, Kawahito Y, Yoshikawa T, Okanoue T. The severity of ultrasonographic findings in nonalcoholic fatty liver disease reflects the metabolic syndrome and visceral fat accumulation. Am J Gastroenterol 2007;102:2708–2715.
   PubMed Web of Science ®Google Scholar
• Mottin CC, Moretto M, Padoin AV, Swarowsky AM, Toneto MG, Glock L, Repetto G. The role of ultrasound in the diagnosis of hepatic steatosis in morbidly obese patients. Obes Surg 2004;14:635–637.
   PubMed Web of Science ®Google Scholar
• Mazhar SM, Shiehmorteza M, Sirlin CB. Noninvasive assessment of hepatic steatosis. Clin Gastroenterol Hepatol 2009;7:135–140.
   PubMed Web of Science ®Google Scholar
• Fishbein MH, Gardner KG, Potter CJ, Schmalbrock P, Smith MA. Introduction of fast MR imaging in the assessment of hepatic steatosis. Magn Reson Imaging 1997; 15:287–293.
   PubMed Web of Science ®Google Scholar
• Charatcharoenwitthaya P, Lindor KD. Role of radiologic modalities in the management of non-alcoholic steatohepatitis. Clin Liver Dis 2007;11:37–54.
   PubMedGoogle Scholar
• Szczepaniak LS, Nurenberg P, Leonard D, Browning JD, Reingold JS, Grundy S, Hobbs HH, Dobbins RL. Magnetic resonance spectroscopy to measure hepatic triglyceride content: prevalence of hepatic steatosis in the general population. Am J Physiol Endocrinol Metab 2005;288:E462–468.
   PubMed Web of Science ®Google Scholar
• 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;53:732–737.
   PubMed Web of Science ®Google Scholar
• 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;94:2467–2474.
   PubMed Web of Science ®Google Scholar
• Adams LA, Lymp JF, St Sauver J, Sanderson SO, Lindor KD, Feldstein A, Angulo P. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology 2005;129:113–121.
   PubMed Web of Science ®Google Scholar
• Powell EE, Cooksley WG, Hanson R, Searle J, Halliday JW, Powell LW. The natural history of nonalcoholic steatohepatitis: a follow-up study of forty-two patients for up to 21 years. Hepatology 1990;11:74–80.
   PubMed Web of Science ®Google Scholar
• Ratziu V, Charlotte F, Heurtier A, Gombert S, Giral P, Bruckert E, Grimaldi A, Capron F, Poynard T. Sampling variability of liver biopsy in nonalcoholic fatty liver disease. Gastroenterology 2005;128:1898–1906.
   PubMed Web of Science ®Google Scholar
• Merriman RB, Ferrell LD, Patti MG, Weston SR, Pabst MS, Aouizerat BE, Bass NM. Correlation of paired liver biopsies in morbidly obese patients with suspected nonalcoholic fatty liver disease. Hepatology 2006;44:874–880.
   PubMed Web of Science ®Google Scholar
• Feldstein AE, Canbay A, Angulo P, Taniai M, Burgart LJ, Lindor KD, Gores GJ. Hepatocyte apoptosis and fas expression are prominent features of human nonalcoholic steatohepatitis. Gastroenterology 2003;125:437–443.
   PubMed Web of Science ®Google Scholar
• Diab DL, Yerian L, Schauer P, Kashyap SR, Lopez R, Hazen SL, Feldstein AE. Cytokeratin 18 fragment levels as a noninvasive biomarker for nonalcoholic steatohepatitis in bariatric surgery patients. Clin Gastroenterol Hepatol 2008;6:1249–1254.
   PubMed Web of Science ®Google Scholar
• Jarrar MH, Baranova A, Collantes R, Ranard B, Stepanova M, Bennett C, Fang Y, Elariny H, Goodman Z, Chandhoke V, Younossi ZM. Adipokines and cytokines in non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2008;27:412–421.
   PubMed Web of Science ®Google Scholar
• Wieckowska A, Zein NN, Yerian LM, Lopez AR, McCullough AJ, Feldstein AE. In vivo assessment of liver cell apoptosis as a novel biomarker of disease severity in nonalcoholic fatty liver disease. Hepatology 2006;44:27–33.
   PubMed Web of Science ®Google Scholar
• Malik R, Chang M, Bhaskar K, Nasser I, Curry M, Schuppan D, Byrnes V, Afdhal N. The clinical utility of biomarkers and the nonalcoholic steatohepatitis CRN liver biopsy scoring system in patients with nonalcoholic fatty liver disease. J Gastroenterol Hepatol 2009;24:564–568.
   PubMed Web of Science ®Google Scholar
• Yilmaz Y, Dolar E, Ulukaya E, Akgoz S, Keskin M, Kiyici M, Aker S, Yilmaztepe A, Gurel S, Gulten M, Nak SG. Soluble forms of extracellular cytokeratin 18 may differentiate simple steatosis from nonalcoholic steatohepatitis. World J Gastroenterol 2007;13:837–844.
   PubMed Web of Science ®Google Scholar
• Younossi ZM, Jarrar M, Nugent C, Randhawa M, Afendy M, Stepanova M, Rafiq N, Goodman Z, Chandhoke V, Baranova A. A novel diagnostic biomarker panel for obesity-related nonalcoholic steatohepatitis (NASH). Obes Surg 2008;18:1430–1437.
   PubMed Web of Science ®Google Scholar
• Poynard T, Ratziu V, Charlotte F, Messous D, Munteanu M, Imbert-Bismut F, Massard J, Bonyhay L, Tahiri M, Thabut D, Cadranel JF, Le Bail B, de Ledinghen V. Diagnostic value of biochemical markers (NashTest) for the prediction of non alcoholo steato hepatitis in patients with non-alcoholic fatty liver disease. BMC Gastroenterol 2006;6:34.
   PubMed Web of Science ®Google Scholar
• Younossi ZM, Page S, Rafiq N, Birerdinc A, Stepanova M, Hossain N, Afendy A, Younoszai Z, Goodman Z, Baranova A. A biomarker panel for non-alcoholic steatohepatitis (NASH) and NASH-related fibrosis. Obes Surg 2011; 21: 431–439.
   PubMed Web of Science ®Google Scholar
• Imbert-Bismut F, Ratziu V, Pieroni L, Charlotte F, Benhamou Y, Poynard T. Biochemical markers of liver fibrosis in patients with hepatitis C virus infection: a prospective study. Lancet 2001;357:1069–1075.
   PubMed Web of Science ®Google Scholar
• Wai CT, Greenson JK, Fontana RJ, Kalbfleisch JD, Marrero JA, Conjeevaram HS, Lok AS. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology 2003;38:518–526.
   PubMed Web of Science ®Google Scholar
• Vallet-Pichard A, Mallet V, Nalpas B, Verkarre V, Nalpas A, Dhalluin-Venier V, Fontaine H, Pol S. FIB-4: an inexpensive and accurate marker of fibrosis in HCV infection. comparison with liver biopsy and fibrotest. Hepatology 2007;46:32–36.
   PubMed Web of Science ®Google Scholar
• 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;7:1104–1112.
   PubMed Web of Science ®Google Scholar
• Guha IN, Parkes J, Roderick P, Chattopadhyay D, Cross R, Harris S, Kaye P, Burt AD, Ryder SD, Aithal GP, Day CP, Rosenberg WM. Noninvasive markers of fibrosis in nonalcoholic fatty liver disease: Validating the European Liver Fibrosis Panel and exploring simple markers. Hepatology 2008;47:455–460.
   PubMed Web of Science ®Google Scholar
• Angulo P, Hui JM, Marchesini G, Bugianesi E, George J, Farrell GC, Enders F, Saksena S, Burt AD, Bida JP, Lindor K, Sanderson SO, Lenzi M, Adams LA, Kench J, Therneau TM, Day CP. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology 2007;45:846–854.
   PubMed Web of Science ®Google Scholar
• Soderberg C, Stal P, Askling J, Glaumann H, Lindberg G, Marmur J, Hultcrantz R. Decreased survival of subjects with elevated liver function tests during a 28-year follow-up. Hepatology 2010;51:595–602.
   PubMed Web of Science ®Google Scholar
• Teli MR, James OF, Burt AD, Bennett MK, Day CP. The natural history of nonalcoholic fatty liver: a follow-up study. Hepatology 1995;22:1714–1719.
   PubMed Web of Science ®Google Scholar
• Dam-Larsen S, Franzmann M, Andersen IB, Christoffersen P, Jensen LB, Sorensen TI, Becker U, Bendtsen F. Long term prognosis of fatty liver: risk of chronic liver disease and death. Gut 2004;53:750–755.
   PubMed Web of Science ®Google Scholar
• Caldwell SH, Hespenheide EE. Subacute liver failure in obese women. Am J Gastroenterol 2002;97:2058–2062.
   PubMed Web of Science ®Google Scholar
• Kuwabara H, Yoshii Y, Mori H, Fujiwara S, Eiraku S, Kojima H, Miyaji K, Hongo Y, Katsu K. Nonalcoholic steatohepatitis-related cirrhosis with subacute liver failure: an autopsy case. Dig Dis Sci 2003;48:1668–1670.
   PubMed Web of Science ®Google Scholar
• Ekstedt M, Franzen LE, Mathiesen UL, Thorelius L, Holmqvist M, Bodemar G, Kechagias S. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 2006;44:865–873.
   PubMed Web of Science ®Google Scholar
• Targher G, Bertolini L, Rodella S, Tessari R, Zenari L, Lippi G, Arcaro G. Nonalcoholic fatty liver disease is independently associated with an increased incidence of cardiovascular events in type 2 diabetic patients. Diabetes Care 2007;30:2119–2121.
   PubMed Web of Science ®Google Scholar
• Evans CD, Oien KA, MacSween RN, Mills PR. Non-alcoholic steatohepatitis: a common cause of progressive chronic liver injury? J Clin Pathol 2002;55:689–692.
   PubMed Web of Science ®Google Scholar
• Sanyal AJ, Banas C, Sargeant C, Luketic VA, Sterling RK, Stravitz RT, Shiffman ML, Heuman D, Coterrell A, Fisher RA, Contos MJ, Mills AS. Similarities and differences in outcomes of cirrhosis due to nonalcoholic steatohepatitis and hepatitis C. Hepatology 2006;43:682–689.
   PubMed Web of Science ®Google Scholar
• Hui JM, Kench JG, Chitturi S, Sud A, Farrell GC, Byth K, Hall P, Khan M, George J. Long-term outcomes of cirrhosis in nonalcoholic steatohepatitis compared with hepatitis C. Hepatology 2003;38:420–427.
   PubMed Web of Science ®Google Scholar
• Guzman G, Brunt EM, Petrovic LM, Chejfec G, Layden TJ, Cotler SJ. Does nonalcoholic fatty liver disease predispose patients to hepatocellular carcinoma in the absence of cirrhosis? Arch Pathol Lab Med 2008;132:1761–1766.
   PubMed Web of Science ®Google Scholar
• Ascha MS, Hanouneh IA, Lopez R, Tamimi TA, Feldstein AF, Zein NN. The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. Hepatology 2010;51:1972–1978.
   PubMed Web of Science ®Google Scholar
• Bhagat V, Mindikoglu AL, Nudo CG, Schiff ER, Tzakis A, Regev A. Outcomes of liver transplantation in patients with cirrhosis due to nonalcoholic steatohepatitis versus patients with cirrhosis due to alcoholic liver disease. Liver Transpl 2009;15:1814–1820.
   PubMed Web of Science ®Google Scholar
• Yalamanchili K, Saadeh S, Klintmalm GB, Jennings LW, Davis GL. Nonalcoholic fatty liver disease after liver transplantation for cryptogenic cirrhosis or nonalcoholic fatty liver disease. Liver Transpl 2010;16:431–439.
   PubMed Web of Science ®Google Scholar
• Malik SM, Devera ME, Fontes P, Shaikh O, Sasatomi E, Ahmad J. Recurrent disease following liver transplantation for nonalcoholic steatohepatitis cirrhosis. Liver Transpl 2009;15:1843–1851.
   PubMed Web of Science ®Google Scholar
• Newsome PN. Recurrence of nonalcoholic fatty liver disease after liver transplantation: it is common, but does it affect outcome? Liver Transpl 2010;16:420–422.
   PubMed Web of Science ®Google Scholar
• Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, 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;120:1640–1645.
   PubMed Web of Science ®Google Scholar
• Perseghin G, Lattuada G, De Cobelli F, Esposito A, Belloni E, Ntali G, Ragogna F, Canu T, Scifo P, Del Maschio A, Luzi L. Increased mediastinal fat and impaired left ventricular energy metabolism in young men with newly found fatty liver. Hepatology 2008;47:51–58.
   PubMed Web of Science ®Google Scholar
• Cali AM, Zern TL, Taksali SE, de Oliveira AM, Dufour S, Otvos JD, Caprio S. Intrahepatic fat accumulation and alterations in lipoprotein composition in obese adolescents: a perfect proatherogenic state. Diabetes Care 2007;30:3093–3098.
   PubMed Web of Science ®Google Scholar
• Hamaguchi M, Kojima T, Takeda N, Nagata C, Takeda J, Sarui H, Kawahito Y, Yoshida N, Suetsugu A, Kato T, Okuda J, Ida K, Yoshikawa T. Nonalcoholic fatty liver disease is a novel predictor of cardiovascular disease. World J Gastroenterol 2007;13:1579–1584.
   PubMed Web of Science ®Google Scholar
• Fraser A, Harris R, Sattar N, Ebrahim S, Smith GD, Lawlor DA. Gamma-glutamyltransferase is associated with incident vascular events independently of alcohol intake: analysis of the British Women’s Heart and Health Study and Meta-Analysis. Arterioscler Thromb Vasc Biol 2007;27:2729–2735.
   PubMed Web of Science ®Google Scholar
• Targher G, Bertolini L, Padovani R, Rodella S, Zoppini G, Zenari L, Cigolini M, Falezza G, Arcaro G. Relations between carotid artery wall thickness and liver histology in subjects with nonalcoholic fatty liver disease. Diabetes Care 2006;29:1325–1330.
   PubMed Web of Science ®Google Scholar
• Kim CH, Park JY, Lee KU, Kim JH, Kim HK. Fatty liver is an independent risk factor for the development of Type 2 diabetes in Korean adults. Diabet Med 2008;25:476–481.
   PubMed Web of Science ®Google Scholar
• Yamada T, Fukatsu M, Suzuki S, Wada T, Yoshida T, Joh T. Fatty liver predicts impaired fasting glucose and type 2 diabetes mellitus in Japanese undergoing a health checkup. J Gastroenterol Hepatol 2010;25:352–356.
   PubMed Web of Science ®Google Scholar
• Ratziu V, Bellentani S, Cortez-Pinto H, Day C, Marchesini G. A position statement on NAFLD/NASH based on the EASL 2009 special conference. J Hepatol 2010;53:372–384.
   PubMed Web of Science ®Google Scholar
• Johnson NA, George J. Fitness versus fatness: moving beyond weight loss in nonalcoholic fatty liver disease. Hepatology 2010;52:370–381.
   PubMed Web of Science ®Google Scholar
• Larson-Meyer DE, Heilbronn LK, Redman LM, Newcomer BR, Frisard MI, Anton S, Smith SR, Alfonso A, Ravussin E. Effect of calorie restriction with or without exercise on insulin sensitivity, beta-cell function, fat cell size, and ectopic lipid in overweight subjects. Diabetes Care 2006;29:1337–1344.
   PubMed Web of Science ®Google Scholar
• Petersen KF, Dufour S, Befroy D, Lehrke M, Hendler RE, Shulman GI. Reversal of nonalcoholic hepatic steatosis, hepatic insulin resistance, and hyperglycemia by moderate weight reduction in patients with type 2 diabetes. Diabetes 2005;54:603–608.
   PubMed Web of Science ®Google Scholar
• Tamura Y, Tanaka Y, Sato F, Choi JB, Watada H, Niwa M, Kinoshita J, Ooka A, Kumashiro N, Igarashi Y, Kyogoku S, Maehara T, Kawasumi M, Hirose T, Kawamori R. Effects of diet and exercise on muscle and liver intracellular lipid contents and insulin sensitivity in type 2 diabetic patients. J Clin Endocrinol Metab 2005;90:3191–3196.
   PubMed Web of Science ®Google Scholar
• Huang MA, Greenson JK, Chao C, Anderson L, Peterman D, Jacobson J, Emick D, Lok AS, Conjeevaram HS. One-year intense nutritional counseling results in histological improvement in patients with non-alcoholic steatohepatitis: a pilot study. Am J Gastroenterol 2005;100:1072–1081.
   PubMed Web of Science ®Google Scholar
• Promrat K, Kleiner DE, Niemeier HM, Jackvony E, Kearns M, Wands JR, Fava JL, Wing RR. Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology 2010;51:121–129.
   PubMed Web of Science ®Google Scholar
• Harrison SA, Fecht W, Brunt EM, Neuschwander-Tetri BA. Orlistat for overweight subjects with nonalcoholic steatohepatitis: A randomized, prospective trial. Hepatology 2009;49:80–86.
   PubMed Web of Science ®Google Scholar
• St George A, Bauman A, Johnston A, Farrell G, Chey T, George J. Independent effects of physical activity in patients with nonalcoholic fatty liver disease. Hepatology. 2009 Jul;50(1):68–76.
   PubMed Web of Science ®Google Scholar
• Sjostrom L, Narbro K, Sjostrom CD, Karason K, Larsson B, Wedel H, Lystig T, Sullivan M, Bouchard C, Carlsson B, Bengtsson C, Dahlgren S, Gummesson A, Jacobson P, Karlsson J, Lindroos AK, Lonroth H, Naslund I, Olbers T, Stenlof K, Torgerson J, Agren G, Carlsson LM. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med 2007;357:741–752.
   PubMed Web of Science ®Google Scholar
• Adams TD, Gress RE, Smith SC, Halverson RC, Simper SC, Rosamond WD, Lamonte MJ, Stroup AM, Hunt SC. Long-term mortality after gastric bypass surgery. N Engl J Med. 2007 Aug 23;357(8):753–61.
   PubMed Web of Science ®Google Scholar
• Lowell JA, Shenoy S, Ghalib R, Caldwell C, White FV, Peters M, Howard TK. Liver transplantation after jejunoileal bypass for morbid obesity. J Am Coll Surg 1997;185:123–127.
   PubMed Web of Science ®Google Scholar
• Requarth JA, Burchard KW, Colacchio TA, Stukel TA, Mott LA, Greenberg ER, Weismann RE. Long-term morbidity following jejunoileal bypass. The continuing potential need for surgical reversal. Arch Surg 1995;130:318–325.
   PubMedGoogle Scholar
• Cotler SJ, Vitello JM, Guzman G, Testa G, Benedetti E, Layden TJ. Hepatic decompensation after gastric bypass surgery for severe obesity. Dig Dis Sci 2004;49:1563–1568.
   PubMed Web of Science ®Google Scholar
• Grimm IS, Schindler W, Haluszka O. Steatohepatitis and fatal hepatic failure after biliopancreatic diversion. Am J Gastroenterol 1992;87:775–779.
   PubMed Web of Science ®Google Scholar
• Mummadi RR, Kasturi KS, Chennareddygari S, Sood GK. Effect of bariatric surgery on nonalcoholic fatty liver disease: systematic review and meta-analysis. Clin Gastroenterol Hepatol 2008;6:1396–1402.
   PubMed Web of Science ®Google Scholar
• Selvin E, Bolen S, Yeh HC, Wiley C, Wilson LM, Marinopoulos SS, et al. Cardiovascular outcomes in trials of oral diabetes medications: a systematic review. Arch Intern Med 2008;168:2070–2080.
   PubMed Web of Science ®Google Scholar
• Musso G, Gambino R, Cassader M, Pagano G. A meta-analysis of randomized trials for the treatment of nonalcoholic fatty liver disease. Hepatology 2010;52:79–104.
   PubMed Web of Science ®Google Scholar
• Sanyal AJ, Chalasani N, Kowdley KV, McCullough A, Diehl AM, Bass NM, Neuschwander-Tetri BA, Lavine JE, Tonascia J, Unalp A, Van Natta M, Clark J, Brunt EM, Kleiner DE, Hoofnagle JH, Robuck PR. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med 2010;362:1675–1685.
   PubMed Web of Science ®Google Scholar
• Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 2007;356:2457–2471.
   PubMed Web of Science ®Google Scholar
• Adams LA, Angulo P. Treatment of non-alcoholic fatty liver disease. Postgrad Med J 2006;82:315–322.
   PubMed Web of Science ®Google Scholar
• Guallar E, Hanley DF, Miller ER 3rd.. An editorial update: Annus horribilis for vitamin E. Ann Intern Med 2005;143:143–145.
   PubMed Web of Science ®Google Scholar
• Lindor KD, Kowdley KV, Heathcote EJ, Harrison ME, Jorgensen R, Angulo P, Lymp JF, Burgart L, Colin P. Ursodeoxycholic acid for treatment of nonalcoholic steatohepatitis: results of a randomized trial. Hepatology 2004;39:770–778.
   PubMed Web of Science ®Google Scholar
• Leuschner UF, Lindenthal B, Herrmann G, Arnold JC, Rossle M, Cordes HJ, Zeuzem S, Hein J, Berg T. High-dose ursodeoxycholic acid therapy for nonalcoholic steatohepatitis: a double-blind, randomized, placebo-controlled trial. Hepatology 2010;52:472–479.
   PubMed Web of Science ®Google Scholar
• Abdelmalek MF, Sanderson SO, Angulo P, Soldevila-Pico C, Liu C, Peter J, Keach J, Cave M, Chen T, McClain CJ, Lindor KD. Betaine for nonalcoholic fatty liver disease: results of a randomized placebo-controlled trial. Hepatology 2009;50:1818–1826.
   PubMed Web of Science ®Google Scholar
• Malaguarnera M, Gargante MP, Russo C, Antic T, Vacante M, Avitabile T, Li Volti G, Galvano F. L-carnitine supplementation to diet: a new tool in treatment of nonalcoholic steatohepatitis–a randomized and controlled clinical trial. Am J Gastroenterol 2010;105:1338–1345.
   PubMed Web of Science ®Google Scholar
• Georgescu EF, Ionescu R, Niculescu M, Mogoanta L, Vancica L. Angiotensin-receptor blockers as therapy for mild-to-moderate hypertension-associated non-alcoholic steatohepatitis. World J Gastroenterol 2009;15:942–954.
   PubMed Web of Science ®Google Scholar
• Zelber-Sagi S, Kessler A, Brazowsky E, Webb M, Lurie Y, Santo M, Leshno M, Blendis L, Halpern Z, Oren R. A double-blind randomized placebo-controlled trial of orlistat for the treatment of nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 2006;4:639–644.
   PubMed Web of Science ®Google Scholar
• Haukeland JW, Konopski Z, Eggesbo HB, von Volkmann HL, Raschpichler G, Bjoro K, Haaland T, Loberg EM, Birkeland K. Metformin in patients with non-alcoholic fatty liver disease: a randomized, controlled trial. Scand J Gastroenterol 2009;44:853–860.
   PubMed Web of Science ®Google Scholar
• Uygun A, Kadayifci A, Isik AT, Ozgurtas T, Deveci S, Tuzun A, Yesilova Z, Gulsen M, Dagalp K. Metformin in the treatment of patients with non-alcoholic steatohepatitis. Aliment Pharmacol Ther 2004;19:537–544.
   PubMed Web of Science ®Google Scholar
• Belfort R, Harrison SA, Brown K, Darland C, Finch J, Hardies J, Balas B, Gastaldelli A, Tio F, Pulcini J, Berria R, Ma JZ, Dwivedi S, Havranek R, Fincke C, DeFronzo R, Bannayan GA, Schenker S, Cusi K. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med 2006;355:2297–2307.
   PubMed Web of Science ®Google Scholar
• Idilman R, Mizrak D, Corapcioglu D, Bektas M, Doganay B, Sayki M, Coban S, Erden E, Soykan I, Emral R, Uysal AR, Ozden A. Clinical trial: insulin-sensitizing agents may reduce consequences of insulin resistance in individuals with non-alcoholic steatohepatitis. Aliment Pharmacol Ther 2008;28:200–208.
   PubMed Web of Science ®Google Scholar
• Omer Z, Cetinkalp S, Akyildiz M, Yilmaz F, Batur Y, Yilmaz C, Akarca U. Efficacy of insulin-sensitizing agents in nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol 2010;22:18–23.
   PubMed Web of Science ®Google Scholar
• Ratziu V, Giral P, Jacqueminet S, Charlotte F, Hartemann-Heurtier A, Serfaty L, Podevin P, Lacorte JM, Bernhardt C, Bruckert E, Grimaldi A, Poynard T. Rosiglitazone for nonalcoholic steatohepatitis: one-year results of the randomized placebo-controlled Fatty Liver Improvement with Rosiglitazone Therapy (FLIRT) Trial. Gastroenterology 2008;135:100–110.
   PubMed Web of Science ®Google Scholar
• Dufour JF, Oneta CM, Gonvers JJ, Bihl F, Cerny A, Cereda JM, Zala JF, Helbling B, Steuerwald M, Zimmermann A. Randomized placebo-controlled trial of ursodeoxycholic acid with vitamin e in nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol 2006;4:1537–1543.
   PubMed Web of Science ®Google Scholar
• Harrison SA, Torgerson S, Hayashi P, Ward J, Schenker S. Vitamin E and vitamin C treatment improves fibrosis in patients with nonalcoholic steatohepatitis. Am J Gastroenterol 2003;98:2485–2490.
   PubMed Web of Science ®Google Scholar
• Nobili V, Manco M, Devito R, Di Ciommo V, Comparcola D, Sartorelli MR, Piemonte F, Marcellini M, Angulo P. Lifestyle intervention and antioxidant therapy in children with nonalcoholic fatty liver disease: a randomized, controlled trial. Hepatology 2008;48:119–128.
   PubMed Web of Science ®Google Scholar
• Nelson A, Torres DM, Morgan AE, Fincke C, Harrison SA. A pilot study using simvastatin in the treatment of nonalcoholic steatohepatitis: A randomized placebo-controlled trial. J Clin Gastroenterol 2009;43:990–994.
   PubMed Web of Science ®Google Scholar