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Journal of Clinical and Experimental Hepatology logoLink to Journal of Clinical and Experimental Hepatology
. 2012 Jul 21;2(2):122–134. doi: 10.1016/S0973-6883(12)60101-7

Non-alcoholic Fatty Liver Disease: East Versus West

Swastik Agrawal 1, Ajay K Duseja 1,*
PMCID: PMC3940312  PMID: 25755421

Abstract

Non-alcoholic fatty liver disease (NAFLD) is an important cause of liver disease worldwide with prevalence ranging from 10% to 30% in various countries. It has become an important cause of unexplained rise in transaminases, cryptogenic cirrhosis, and cryptogenic hepatocellular carcinoma. Pathogenesis is related to obesity, insulin resistance, oxidative stress, lipotoxicity, and resultant inflammation in the liver progressing to fibrosis. Pharmacological treatment in patients with NAFLD is still evolving and the treatment of these patients rests upon lifestyle modification with diet and exercise being the cornerstones of therapy. While there are many similarities between patients with NAFLD from Asia and the West, there are certain features which make the patients with NAFLD from Asia stand apart. This review highlights the data on NAFLD from Asia comparing it with the data from the West.

Keywords: Cirrhosis, diabetes mellitus, gene mutations, insulin resistance, metabolic syndrome, non-alcoholic steatohepatitis

Abbreviations: ALT, alanine aminotransferases; APO C3, apolipoprotein C3; CC, cryptogenic cirrhosis; CLD, chronic liver disease; DM, diabetes mellitus; FRAP, ferric-reducing ability of plasma; GSH, glutathione; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HDL, high-density lipoprotein; HTN, hypertension; IR, insulin resistance; ITT, insulin tolerance test; MS, metabolic syndrome; NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic steatohepatitis; PCC, protein carbonyl; PNPLA3, patatin-like phospholipase domain-containing protein 3; SOD, superoxide dismutase; TBARS, thiobarbituric acid reactive substances; TG, triglyceride; TGF-β, transforming growth factor-beta; TNF-α, tumor necrosis factor-alfa; VLDL, very low density lipoproteins

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References

  • 1.Ludwig J, Viggiano TR, McGill DB, Oh BJ. Nonalcoholic steatohepatitis. Mayo Clinic experience with a hitherto unnamed disease. Mayo Clin Proc. 1980;55:434–438. [PubMed] [Google Scholar]
  • 2.Amarapurkar DN, Hashimoto E, Lesmana LA, Sollano JD, Chen PJ, Goh KL, Asia-Pacific Working Party on NAFLD How common is non-alcoholic fatty liver disease in the Asia-Pacific region and are there local differences? J Gastroenterol Hepatol. 2007;22:788–793. doi: 10.1111/j.1440-1746.2007.05042.x. [DOI] [PubMed] [Google Scholar]
  • 3.Chitturi S, Wong VW, Farrell G. Nonalcoholic fatty liver in Asia: firmly entrenched and rapidly gaining ground. J Gastroenterol Hepatol. 2011;26(Suppl 1):163–172. doi: 10.1111/j.1440-1746.2010.06548.x. [DOI] [PubMed] [Google Scholar]
  • 4.Das K, Das K, Mukherjee PS. Nonobese population in a developing country has a high prevalence of nonalcoholic fatty liver and significant liver disease. Hepatology. 2010;51:1593–1602. doi: 10.1002/hep.23567. [DOI] [PubMed] [Google Scholar]
  • 5.Amarapurkar D, Kamani P, Patel N. Prevalence of non-alcoholic fatty liver disease: population based study. Ann Hepatol. 2007;6:161–163. [PubMed] [Google Scholar]
  • 6.Mohan V, Farooq S, Deepa M, Ravikumar R, Pitchumoni CS. Prevalence of non-alcoholic fatty liver disease in urban south Indians in relation to different grades of glucose intolerance and metabolic syndrome. Diabetes Res Clin Pract. 2009;84:84–91. doi: 10.1016/j.diabres.2008.11.039. [DOI] [PubMed] [Google Scholar]
  • 7.Singh SP, Nayak S, Swain M. Prevalence of nonalcoholic fatty liver disease in coastal eastern India: a preliminary ultrasonographic survey. Trop Gastroenterol. 2004;25:76–79. [PubMed] [Google Scholar]
  • 8.Sanyal AJ. American Gastroenterological Association. AGA technical review on nonalcoholic fatty liver disease. Gastroenterology. 2002;123:1705–1725. doi: 10.1053/gast.2002.36572. [DOI] [PubMed] [Google Scholar]
  • 9.Weston SR, Leyden W, Murphy R. Racial and ethnic distribution of nonalcoholic fatty liver in persons with newly diagnosed chronic liver disease. Hepatology. 2005;41:372–379. doi: 10.1002/hep.20554. [DOI] [PubMed] [Google Scholar]
  • 10.Petersen KF, Dufour S, Feng J. Increased prevalence of insulin resistance and nonalcoholic fatty liver disease in Asian-Indian men. Proc Natl Acad Sci USA. 2006;103:18273–18277. doi: 10.1073/pnas.0608537103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Targher G, Bertolini L, Padovani R. Prevalence of nonalcoholic fatty liver disease and its association with cardiovascular disease among type 2 diabetic patients. Diabetes Care. 2007;30:1212–1218. doi: 10.2337/dc06-2247. [DOI] [PubMed] [Google Scholar]
  • 12.Williams CD, Stengel J, Asike MI. 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. doi: 10.1053/j.gastro.2010.09.038. [DOI] [PubMed] [Google Scholar]
  • 13.Bernal-Reyes R, Sáenz-Labra A, Bernardo-Escudero R. Prevalence of non-alcoholic steatohepatitis. Comparative study with diabetic patients. Rev Gastroenterol Mex. 2000;65:58–62. [PubMed] [Google Scholar]
  • 14.Duseja A, Bhansali A, Bhadada S, Jain P, Dhiman RK, Chawla Y. Nonalcoholic fatty liver disease in patients with recent onset type 2 diabetes mellitus [Abstract] J Gastroenterol Hepatol. 2004;19(Suppl):A402. [Google Scholar]
  • 15.Gupte P, Amarapurkar D, Agal S. Nonalcoholic steatohepatitis in type 2 diabetes mellitus. J Gastroenterol Hepatol. 2004;19:854–858. doi: 10.1111/j.1440-1746.2004.03312.x. [DOI] [PubMed] [Google Scholar]
  • 16.Merat S, Yarahmadi S, Tahaghoghi S. Prevalence of fatty liver disease among type 2 diabetes mellitus patients and its relation to insulin resistance. Mid East J Dig Dis. 2009;1:74–79. [Google Scholar]
  • 17.Park SH, Jeon WK, Kim SH. Prevalence and risk factors of non-alcoholic fatty liver disease among Korean adults. J Gastroenterol Hepatol. 2006;21:138–143. doi: 10.1111/j.1440-1746.2005.04086.x. [DOI] [PubMed] [Google Scholar]
  • 18.Ong JP, Elariny H, Collantes R. Predictors of nonalcoholic steatohepatitis and advanced fibrosis in morbidly obese patients. Obes Surg. 2005;15:310–315. doi: 10.1381/0960892053576820. [DOI] [PubMed] [Google Scholar]
  • 19.Kojima S, Watanabe N, Numata M, Ogawa T, Matsuzaki S. Increase in the prevalence of fatty liver in Japan over the past 12 years: analysis of clinical background. J Gastroenterol. 2003;38:954–961. doi: 10.1007/s00535-003-1178-8. [DOI] [PubMed] [Google Scholar]
  • 20.Fan JG, Li F, Cai XB, Peng YD, Ao QH, Gao Y. The importance of metabolic factors for the increasing prevalence of fatty liver in Shanghai factory workers. J Gastroenterol Hepatol. 2007;22:663–668. doi: 10.1111/j.1440-1746.2007.04892.x. [DOI] [PubMed] [Google Scholar]
  • 21.Hasan I, Gani RA, Machmud R. Prevalence and risk factors for nonalcoholic fatty liver in Indonesia [Abstract] J Gastroenterol Hepatol. 2002;17(Suppl):S154. [Google Scholar]
  • 22.Huang HL, Lin WY, Lee LT, Wang HH, Lee WJ, Huang KC. Metabolic syndrome is related to nonalcoholic steatohepatitis in severely obese subjects. Obes Surg. 2007;17:1457–1463. doi: 10.1007/s11695-008-9423-0. [DOI] [PubMed] [Google Scholar]
  • 23.Clark JM, Brancati FL, Diehl AM. The prevalence and etiology of elevated aminotransferase levels in the United States. Am J Gastroenterol. 2003;98:960–967. doi: 10.1111/j.1572-0241.2003.07486.x. [DOI] [PubMed] [Google Scholar]
  • 24.de Lédinghen V, Ratziu V, Causse X. Association Française pour l'Etude du Foie Groupe Epidémiologie et Evaluation; Association Nationale des Gastroentérologues des Hôpitauxgénéraux de France. Diagnostic and predictive factors of significant liver fibrosis and minimal lesions in patients with persistent unexplained elevated transaminases. A prospective multicenter study. J Hepatol. 2006;45:592–599. doi: 10.1016/j.jhep.2006.05.008. [DOI] [PubMed] [Google Scholar]
  • 25.Madan K, Batra Y, Panda SK. Role of polymerase chain reaction and liver biopsy in the evaluation of patients with asymptomatic transaminitis: implications in diagnostic approach. J Gastroenterol Hepatol. 2004;19:1291–1299. doi: 10.1111/j.1440-1746.2004.03446.x. [DOI] [PubMed] [Google Scholar]
  • 26.Dhiman RK, Duseja A. Nonalcoholic fatty liver disease. In: Gupta SB. J Assoc Physicians India. Medicine Update. 2005;15:469–475. [Google Scholar]
  • 27.Jamali R, Khonsari M, Merat S. Persistent alanine aminotransferase elevation among the general Iranian population: prevalence and causes. World J Gastroenterol. 2008;14:2867–2871. doi: 10.3748/wjg.14.2867. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Chen CH, Huang MH, Yang JC. Prevalence and etiology of elevated serum alanine aminotransferase level in an adult population in Taiwan. J Gastroenterol Hepatol. 2007;22:1482–1489. doi: 10.1111/j.1440-1746.2006.04615.x. [DOI] [PubMed] [Google Scholar]
  • 29.Mofrad P, Contos MJ, Haque M. Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values. Hepatology. 2003;37:1286–1292. doi: 10.1053/jhep.2003.50229. [DOI] [PubMed] [Google Scholar]
  • 30.Amarapurkar DN, Patel ND. Clinical spectrum and natural history of non-alcoholic steatohepatitis with normal alanine aminotransferases values. Trop Gastroenterol. 2004;25:130–134. [PubMed] [Google Scholar]
  • 31.Caldwell SH, Oelsner DH, Iezzoni JC, Hespenheide EE, Battle EH, Driscoll CJ. Cryptogenic cirrhosis: clinical characterization and risk factors for underlying disease. Hepatology. 1999;29:664–666. doi: 10.1002/hep.510290347. [DOI] [PubMed] [Google Scholar]
  • 32.Poonawala A, Nair SP, Thuluvath PJ. Prevalence of obesity and diabetes in patients with cryptogenic cirrhosis: a casecontrol study. Hepatology. 2000;32:689–692. doi: 10.1053/jhep.2000.17894. [DOI] [PubMed] [Google Scholar]
  • 33.Ayata G, Gordon FD, Lewis WD. Cryptogenic cirrhosis: clinicopathologic findings at and after liver transplantation. Hum Pathol. 2002;33:1098–1104. doi: 10.1053/hupa.2002.129419. [DOI] [PubMed] [Google Scholar]
  • 34.Amarapurkar D, Das HS. Chronic liver disease in diabetes mellitus. Trop Gastroenterol. 2002;23:3–5. [PubMed] [Google Scholar]
  • 35.Nayak NC, Vasdev N, Saigal S, Soin AS. End-stage nonalcoholic fatty liver disease: evaluation of pathomorphologic features and relationship to cryptogenic cirrhosis from study of explant livers in a living donor liver transplant program. Hum Pathol. 2010;41:425–430. doi: 10.1016/j.humpath.2009.06.021. [DOI] [PubMed] [Google Scholar]
  • 36.Duseja A, Sharma BK, Kumar A. Nonalcoholic fatty liver in a developing country is responsible for significant liver disease. Hepatology. 2010;52:2248–2249. doi: 10.1002/hep.23838. [DOI] [PubMed] [Google Scholar]
  • 37.Michitaka K, Nishiguchi S, Aoyagi Y, Hiasa Y, Tokumoto Y, Onji M, Japan Etiology of Liver Cirrhosis Study Group Etiology of liver cirrhosis in Japan: a nationwide survey. J Gastroenterol. 2010;45:86–94. doi: 10.1007/s00535-009-0128-5. [DOI] [PubMed] [Google Scholar]
  • 38.Marrero JA, Fontana RJ, Su GL, Conjeevaram HS, Emick DM, Lok AS. NAFLD may be a common underlying liver disease in patients with hepatocellular carcinoma in the United States. Hepatology. 2002;36:1349–1354. doi: 10.1053/jhep.2002.36939. [DOI] [PubMed] [Google Scholar]
  • 39.Das D, Chattopadhyay D, Aslam T. NAFLD and the changing face of hepatocellular cancer (HCC) [Abstract] Gut. 2011;60(Suppl 1):A243. [Google Scholar]
  • 40.Bugianesi E, Leone N, Vanni E. Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology. 2002;123:134–140. doi: 10.1053/gast.2002.34168. [DOI] [PubMed] [Google Scholar]
  • 41.Abe H, Yoshizawa K, Kitahara T, Aizawa R, Matsuoka M, Aizawa Y. Etiology of non-B non-C hepatocellular carcinoma in the eastern district of Tokyo. J Gastroenterol. 2008;43:967–974. doi: 10.1007/s00535-008-2264-8. [DOI] [PubMed] [Google Scholar]
  • 42.Oh KC, Park SH, Park JC. Is the prevalence of cryptogenic hepatocellular carcinoma increasing in Korea? Korean J Gastroenterol. 2005;45:45–51. [PubMed] [Google Scholar]
  • 43.Song HY, Lee HK, Lee JS. Risk factors of cryptogenic hepatocellular carcinoma in patients with low body mass index or without metabolic syndrome. Korean J Intern Med. 2012;27:47–52. doi: 10.3904/kjim.2012.27.1.47. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 44.Takuma Y, Nouso K. Nonalcoholic steatohepatitis-associated hepatocellular carcinoma: our case series and literature review. World J Gastroenterol. 2010;16:1436–1441. doi: 10.3748/wjg.v16.i12.1436. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 45.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. doi: 10.1002/hep.23527. [DOI] [PubMed] [Google Scholar]
  • 46.Angulo P, Keach JC, Batts KP, Lindor KD. Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology. 1999;30:1356–1362. doi: 10.1002/hep.510300604. [DOI] [PubMed] [Google Scholar]
  • 47.Hui AY, Wong VW, Chan HL. Histological progression of nonalcoholic fatty liver disease in Chinese patients. Aliment Pharmacol Ther. 2005;21:407–413. doi: 10.1111/j.1365-2036.2005.02334.x. [DOI] [PubMed] [Google Scholar]
  • 48.Adams LA, Lymp JF, St Sauver J. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology. 2005;126:113–121. doi: 10.1053/j.gastro.2005.04.014. [DOI] [PubMed] [Google Scholar]
  • 49.Matteoni CA, Younossi ZM, Gramlich T, Boparai N, Liu YC, McCullough AJ. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology. 2005;129:113–121. doi: 10.1016/s0016-5085(99)70506-8. [DOI] [PubMed] [Google Scholar]
  • 50.Khurram M, Ashraf MM. A clinical and biochemical profile of biopsy-proven non-alcoholic fatty liver disease subjects. J Coll Physicians Surg Pak. 2007;17:531–534. [PubMed] [Google Scholar]
  • 51.De Lusong MA, Labio E, Daez L, Gloria V. Non-alcoholic fatty liver disease in the Philippines: comparable with other nations? World J Gastroenterol. 2008;14:913–917. doi: 10.3748/wjg.14.913. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 52.Shen L, Fan JG, Shao Y. Prevalence of nonalcoholic fatty liver among administrative officers in Shanghai: an epidemiological survey. World J Gastroenterol. 2003;9:1106–1110. doi: 10.3748/wjg.v9.i5.1106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 53.Duseja A, Das A, Das R. The clinicopathological profile of Indian patients with nonalcoholic fatty liver disease (NAFLD) is different from that in the West. Dig Dis Sci. 2007;52:2368–2374. doi: 10.1007/s10620-006-9136-y. [DOI] [PubMed] [Google Scholar]
  • 54.Duseja A, Das A, Dhiman RK. Indian patients with nonalcoholic fatty liver disease presenting with raised transaminases are different at presentation. World J Gastroenterol. 2007;13:649–650. doi: 10.3748/wjg.v13.i4.649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 55.Dassanayake AS, Kasturiratne A, Rajindrajith S. Prevalence and risk factors for non-alcoholic fatty liver disease among adults in an urban Sri Lankan population. J Gastroenterol Hepatol. 2009;24:1284–1288. doi: 10.1111/j.1440-1746.2009.05831.x. [DOI] [PubMed] [Google Scholar]
  • 56.Willett WC, Dietz WH, Colditz GA. Guidelines for healthy weight. N Engl J Med. 1999;341:427–434. doi: 10.1056/NEJM199908053410607. [DOI] [PubMed] [Google Scholar]
  • 57.Amarapurkar DN, Amarapurkar AD. Nonalcoholic steatohepatitis: clinicopathological profile. J Assoc Phys India. 2000;48:311–313. [PubMed] [Google Scholar]
  • 58.Agarwal SR, Malhotra V, Sakhuja P, Sarin SK. Clinical, biochemical and histological profile of nonalcoholic steatohepatitis. Indian J Gastroenterol. 2001;20:183–186. [PubMed] [Google Scholar]
  • 59.Duseja A, Murlidharan R, Bhansali A. Assessment of insulin resistance and effect of metformin in nonalcoholic steatohepatitis-a preliminary report. Indian J Gastroenterol. 2004;23:12–15. [PubMed] [Google Scholar]
  • 60.Steering Committee of the Western Pacific region of the World Health Organization, The International Association for the study of Obesity and the International Obesity Task Force. The Asia-Pacific perspective: redefining obesity and its treatment. Health Communications Australia Pty Limited: Melbourne 2000. ISBN 0-9577082-1-1.
  • 61.Deurenberg-Yap M, Chew SK, Deurenberg P. Elevated body fat percentage and cardiovascular risks at low body mass index levels among Singaporean Chinese, Malays and Indians. Obes Rev. 2002;3:209–215. doi: 10.1046/j.1467-789x.2002.00069.x. [DOI] [PubMed] [Google Scholar]
  • 62.Misra A, Misra R. Asian Indians and insulin resistance syndrome: global perspective. Metab Syndr Relat Disord. 2003;1:277–283. doi: 10.1089/1540419031361390. [DOI] [PubMed] [Google Scholar]
  • 63.Ko GT, Chan JC, Cockram CS, Woo J. Prediction of hypertension, diabetes, dyslipidaemia or albuminuria using simple anthropometric indexes in Hong Kong Chinese. Int J Obes Relat Metab Disord. 1999;23:1136–1142. doi: 10.1038/sj.ijo.0801043. [DOI] [PubMed] [Google Scholar]
  • 64.Misra A, Vikram NK. Clinical and pathophysiological consequences of abdominal adiposity and abdominal adipose tissue depots. Nutrition. 2003;19:457–466. doi: 10.1016/s0899-9007(02)01003-1. [DOI] [PubMed] [Google Scholar]
  • 65.Misra A, Chowbey P, Makkar BM. Consensus statement for diagnosis of obesity, abdominal obesity and the metabolic syndrome for Asian Indians and recommendations for physical activity, medical and surgical management. J Assoc Physicians India. 2009;57:163–170. [PubMed] [Google Scholar]
  • 66.Tilg H, Diehl AM. Cytokines in alcoholic and nonalcoholic steatohepatitis. N Engl J Med. 2000;343:1467–1476. doi: 10.1056/NEJM200011163432007. [DOI] [PubMed] [Google Scholar]
  • 67.Marchesini G, Brizi M, Morselli-Labate AM. Association of nonalcoholic fatty liver disease with insulin resistance. Am J Med. 1999;107:450–455. doi: 10.1016/s0002-9343(99)00271-5. [DOI] [PubMed] [Google Scholar]
  • 68.Angelico F, Del Ben M, Conti R. Insulin resistance, the metabolic syndrome, and nonalcoholic fatty liver disease. J Clin Endocrinol Metab. 2005;90:1578–1582. doi: 10.1210/jc.2004-1024. [DOI] [PubMed] [Google Scholar]
  • 69.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. doi: 10.1002/hep.20280. [DOI] [PubMed] [Google Scholar]
  • 70.Chitturi S, Abeygunasekera S, Farrell GC. NASH and insulin resistance: insulin hypersecretion and specific association with the insulin resistance syndrome. Hepatology. 2002;35:373–379. doi: 10.1053/jhep.2002.30692. [DOI] [PubMed] [Google Scholar]
  • 71.Speliotes EK, Massaro JM, Hoffmann U. Fatty liver is associated with dyslipidemia and dysglycemia independent of visceral fat: the Framingham Heart Study. Hepatology. 2010;51:1979–1987. doi: 10.1002/hep.23593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 72.Madan K, Batra Y, Gupta SD. Non-alcoholic fatty liver disease may not be a severe disease at presentation among Asian Indians. World J Gastroenterol. 2006;12:3400–3405. doi: 10.3748/wjg.v12.i21.3400. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 73.Amarapurkar DN, Patel ND. Prevalence of metabolic syndrome in non-diabetic and non-cirrhotic patients with non-alcoholic steatohepatitis. Trop Gastroenterol. 2004;25:125–129. [PubMed] [Google Scholar]
  • 74.Sreenivasa Baba C, Alexander G, Kalyani B. Effect of exercise and dietary modification on serum aminotransferase levels in patients with nonalcoholic steatohepatitis. J Gastroenterol Hepatol. 2006;2:191–198. doi: 10.1111/j.1440-1746.2005.04233.x. [DOI] [PubMed] [Google Scholar]
  • 75.Sung KC, Ryan MC, Wilson AM. The severity of nonalcoholic fatty liver disease is associated with increased cardiovascular risk in a large cohort of non-obese Asian subjects. Atherosclerosis. 2009;203:581–586. doi: 10.1016/j.atherosclerosis.2008.07.024. [DOI] [PubMed] [Google Scholar]
  • 76.Shibata M, Kihara Y, Taguchi M, Tashiro M, Otsuki M. Nonalcoholic fatty liver disease is a risk factor for type 2 diabetes in middle-aged Japanese men. Diabetes Care. 2007;30:2940–2944. doi: 10.2337/dc07-0792. [DOI] [PubMed] [Google Scholar]
  • 77.Fan JG, Li F, Cai XB, Peng YD, Ao QH, Gao Y. Effects of nonalcoholic fatty liver disease on the development of metabolic disorders. J Gastroenterol Hepatol. 2007;22:1086–1091. doi: 10.1111/j.1440-1746.2006.04781.x. [DOI] [PubMed] [Google Scholar]
  • 78.Rafiq N, Bai C, Fang Y. Long-term follow-up of patients with nonalcoholic fatty liver. Clin Gastroenterol Hepatol. 2009;7:234–238. doi: 10.1016/j.cgh.2008.11.005. [DOI] [PubMed] [Google Scholar]
  • 79.Marchesini G, Bugianesi E, Forlani G. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology. 2003;37:917–923. doi: 10.1053/jhep.2003.50161. [DOI] [PubMed] [Google Scholar]
  • 80.Fan JG, Zhu J, Li XJ. Fatty liver and the metabolic syndrome among Shanghai adults. J Gastroenterol Hepatol. 2005;20:1825–1832. doi: 10.1111/j.1440-1746.2005.04058.x. [DOI] [PubMed] [Google Scholar]
  • 81.Videla LA, Rodrigo R, Orellana M. Oxidative stress-related parameters in the liver of non-alcoholic fatty liver disease patients. Clin Sci (Lond) 2004;106:261–268. doi: 10.1042/CS20030285. [DOI] [PubMed] [Google Scholar]
  • 82.Weltman MD, Farrell GC, Hall P, Ingelman-Sundberg M, Liddle C. Hepatic cytochrome P450 2E1 is increased in patients with nonalcoholic steatohepatitis. Hepatology. 1998;27:128–133. doi: 10.1002/hep.510270121. [DOI] [PubMed] [Google Scholar]
  • 83.Musso G, Gambino R, De Michieli F. Nitrosative stress predicts the presence and severity of nonalcoholic fatty liver at different stages of the development of insulin resistance and metabolic syndrome: possible role of vitamin A intake. Am J Clin Nutr. 2007;86:661–671. doi: 10.1093/ajcn/86.3.661. [DOI] [PubMed] [Google Scholar]
  • 84.Madan K, Bhardwaj P, Thareja S, Gupta SD, Saraya A. Oxidant stress and antioxidant status among patients with nonalcoholic fatty liver disease (NAFLD) J Clin Gastroenterol. 2006;40:930–935. doi: 10.1097/01.mcg.0000212608.59090.08. [DOI] [PubMed] [Google Scholar]
  • 85.Narasimhan S, Gokulakrishnan K, Sampathkumar R. Oxidative stress is independently associated with non-alcoholic fatty liver disease (NAFLD) in subjects with and without type 2 diabetes. Clin Biochem. 2010;43:815–821. doi: 10.1016/j.clinbiochem.2010.04.003. [DOI] [PubMed] [Google Scholar]
  • 86.Sanyal AJ, Campbell-Sargent C, Mirshahi F. Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. Gastroenterology. 2001;120:1183–1192. doi: 10.1053/gast.2001.23256. [DOI] [PubMed] [Google Scholar]
  • 87.Pérez-Carreras M, Del Hoyo P, Martín MA. Defective hepatic mitochondrial respiratory chain in patients with nonalcoholic steatohepatitis. Hepatology. 2003;38:999–1007. doi: 10.1053/jhep.2003.50398. [DOI] [PubMed] [Google Scholar]
  • 88.Kowdley KV, Belt P, Wilson LA, NASH Clinical Research Network Serum ferritin is an independent predictor of histologic severity and advanced fibrosis in patients with nonalcoholic fatty liver disease. Hepatology. 2012;55:77–85. doi: 10.1002/hep.24706. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 89.Day CP, James OF. Steatohepatitis: a tale of two “hits”? Gastroenterology. 1998;114:842–845. doi: 10.1016/s0016-5085(98)70599-2. [DOI] [PubMed] [Google Scholar]
  • 90.Graham RM, Chua AC, Carter KW. Hepatic iron loading in mice increases cholesterol bio-synthesis. Hepatology. 2010;52:462–471. doi: 10.1002/hep.23712. [DOI] [PubMed] [Google Scholar]
  • 91.Valenti L, Fracanzani AL, Bugianesi E. HFE genotype, parenchymal iron accumulation, and liver fibrosis in patients with nonalcoholic fatty liver disease. Gastroenterology. 2010;138:905–912. doi: 10.1053/j.gastro.2009.11.013. [DOI] [PubMed] [Google Scholar]
  • 92.Bonkovsky HL, Jawaid Q, Tortorelli K. Non-alcoholic steatohepatitis and iron: increased prevalence of mutations of the HFE gene in non-alcoholic steatohepatitis. J Hepatol. 1999;31:421–429. doi: 10.1016/s0168-8278(99)80032-4. [DOI] [PubMed] [Google Scholar]
  • 93.Duseja A, Das R, Das A, Dhiman RK, Chawla Y, Garewal G. Serum iron levels and hepatic iron overload in patients with nonalcoholic steatohepatitis. Dig Dis Sci. 2006;51:1730–1731. doi: 10.1007/s10620-005-9041-9. [DOI] [PubMed] [Google Scholar]
  • 94.Duseja A, Das R, Nanda M, Das A, Garewal G, Chawla Y. Nonalcoholic steatohepatitis in Asian Indians is neither associated with iron overload nor with HFE gene mutations. World J Gastroenterol. 2005;11:393–395. doi: 10.3748/wjg.v11.i3.393. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 95.Yamauchi N, Itoh Y, Tanaka Y. Clinical characteristics and prevalence of GB virus C, SEN virus, and HFE mutation in Japanese patients with nonalcoholic steatohepatitis. J Gastroenterol. 2004;39:654–660. doi: 10.1007/s00535-003-1361-y. [DOI] [PubMed] [Google Scholar]
  • 96.Chitturi S, Weltman M, Farrell GC. HFE mutations, hepatic iron, and fibrosis: ethnic-specific association of NASH with C282Y but not with fibrotic severity. Hepatology. 2002;36:142–149. doi: 10.1053/jhep.2002.33892. [DOI] [PubMed] [Google Scholar]
  • 97.Miller M, Rhyne J, Chen H. APOC3 promoter polymorphisms C-482T and T-455C are associated with the metabolic syndrome. Arch Med Res. 2007;38:444–451. doi: 10.1016/j.arcmed.2006.10.013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 98.Petersen KF, Dufour S, Hariri A. Apolipoprotein C3 gene variants in nonalcoholic fatty liver disease. N Engl J Med. 2010;362:1082–1089. doi: 10.1056/NEJMoa0907295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 99.Kozlitina J, Boerwinkle E, Cohen JC, Hobbs HH. Dissociation between APOC3 variants, hepatic triglyceride content and insulin resistance. Hepatology. 2011;53:467–474. doi: 10.1002/hep.24072. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 100.Valenti L, Nobili V, Al-Serri A. The APOC3 T-455C and C-482T promoter region polymorphisms are not associated with the severity of liver damage independently of PNPLA3 I148M genotype in patients with nonalcoholic fatty liver. J Hepatol. 2011;55:1409–1414. doi: 10.1016/j.jhep.2011.03.035. [DOI] [PubMed] [Google Scholar]
  • 101.Li Y, Xing C, Cohen JC, Hobbs HH. Genetic variant in PNPLA3 is associated with nonalcoholic fatty liver disease in China. Hepatology. 2012;55:327–328. doi: 10.1002/hep.24659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 102.Peter A, Kantartzis K, Machicao F. Visceral obesity modulates the impact of apolipoprotein C3 gene variants on liver fat content. Int J Obes (Lond) 2011 doi: 10.1038/ijo.2011.154. [Epub ahead of print]. [DOI] [PubMed] [Google Scholar]
  • 103.Duseja A, Aggarwal R. APOC3 and PNPLA3 in non-alcoholic fatty liver disease: need to clear the air. J Gastroenterol Hepatol. 2012;27:848–851. doi: 10.1111/j.1440-1746.2012.07103.x. [DOI] [PubMed] [Google Scholar]
  • 104.Cox AJ, Wing MR, Carr JJ. Association of PNPLA3 SNP rs738409 with liver density in African Americans with type 2 diabetes mellitus. Diabetes Metab. 2011;37:452–455. doi: 10.1016/j.diabet.2011.05.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 105.Romeo S, Kozlitina J, Xing C. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet. 2008;40:1461–1465. doi: 10.1038/ng.257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 106.Valenti L, Al-Serri A, Daly AK. 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. doi: 10.1002/hep.23622. [DOI] [PubMed] [Google Scholar]
  • 107.Valenti L, Alisi A, Galmozzi E. I148M patatin-like phospholipase domain-containing 3 gene variant and severity of pediatric nonalcoholic fatty liver disease. Hepatology. 2010;52:1274–1280. doi: 10.1002/hep.23823. [DOI] [PubMed] [Google Scholar]
  • 108.Zain SM, Mohamed R, Mahadeva S. A multi-ethnic study of a PNPLA3 gene variant and its association with disease severity in non-alcoholic fatty liver disease. Hum Genet. 2012 doi: 10.1007/s00439-012-1141-y. [Epub ahead of print]. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 109.Sookoian S, Pirola CJ. Meta-analysis of the influence of I148M variant of patatin-like phospholipase domain containing 3 gene (PNPLA3) on the susceptibility and histological severity of nonalcoholic fatty liver disease. Hepatology. 2011;53:1883–1894. doi: 10.1002/hep.24283. [DOI] [PubMed] [Google Scholar]
  • 110.Wong VW, Vergniol J, Wong GL. Diagnosis of fibrosis and cirrhosis using liver stiffness measurement in nonalcoholic fatty liver disease. Hepatology. 2010;51:454–462. doi: 10.1002/hep.23312. [DOI] [PubMed] [Google Scholar]
  • 111.Park JW, Jeong G, Kim SJ, Kim MK, Park SM. Predictors reflecting the pathological severity of non-alcoholic fatty liver disease: comprehensive study of clinical and immunohistochemical findings in younger Asian patients. J Gastroenterol Hepatol. 2007;22:491–497. doi: 10.1111/j.1440-1746.2006.04758.x. [DOI] [PubMed] [Google Scholar]
  • 112.Wong VW, Wong GL, Tsang SW. Metabolic and histological features of non-alcoholic fatty liver disease patients with different serum alanine aminotransferase levels. Aliment Pharmacol Ther. 2009;29:387–396. doi: 10.1111/j.1365-2036.2008.03896.x. [DOI] [PubMed] [Google Scholar]
  • 113.Wong VW, Wong GL, Choi PC. Disease progression of nonalcoholic fatty liver disease: a prospective study with paired liver biopsies at 3 years. Gut. 2010;59:969–974. doi: 10.1136/gut.2009.205088. [DOI] [PubMed] [Google Scholar]
  • 114.Harrison SA, Torgerson S, Hayashi PH. The natural history of nonalcoholic fatty liver disease: a clinical histopathological study. Am J Gastroenterol. 2003;98:2042–2047. doi: 10.1111/j.1572-0241.2003.07659.x. [DOI] [PubMed] [Google Scholar]
  • 115.Farrell GC, Larter CZ. Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology. 2006;43(2 Suppl 1):S99–S112. doi: 10.1002/hep.20973. [DOI] [PubMed] [Google Scholar]
  • 116.Yatsuji S, Hashimoto E, Tobari M, Taniai M, Tokushige K, Shiratori K. Clinical features and outcomes of cirrhosis due to non-alcoholic steatohepatitis compared with cirrhosis caused by chronic hepatitis. J Gastroenterol Hepatol. 2009;24:248–254. doi: 10.1111/j.1440-1746.2008.05640.x. [DOI] [PubMed] [Google Scholar]
  • 117.Hashimoto E, Yatsuji S, Tobari M. Hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. J Gastroenterol. 2009;44(Suppl 19):89–95. doi: 10.1007/s00535-008-2262-x. [DOI] [PubMed] [Google Scholar]
  • 118.Starley BQ, Calcagno CJ, Harrison SA. Nonalcoholic fatty liver disease and hepatocellular carcinoma: a weighty connection. Hepatology. 2010;51:1820–1832. doi: 10.1002/hep.23594. [DOI] [PubMed] [Google Scholar]
  • 119.Ong JP, Pitts A, Younossi ZM. Increased overall mortality and liver-related mortality in non-alcoholic fatty liver disease. J Hepatol. 2008;49:608–612. doi: 10.1016/j.jhep.2008.06.018. [DOI] [PubMed] [Google Scholar]
  • 120.Sookoian S, Pirola CJ. Non-alcoholic fatty liver disease is strongly associated with carotid atherosclerosis: a systematic review. J Hepatol. 2008;49:600–607. doi: 10.1016/j.jhep.2008.06.012. [DOI] [PubMed] [Google Scholar]
  • 121.Targher G, Day CP, Bonora E. Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. N Engl J Med. 2010;363:1341–1350. doi: 10.1056/NEJMra0912063. [DOI] [PubMed] [Google Scholar]
  • 122.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;50:68–76. doi: 10.1002/hep.22940. [DOI] [PubMed] [Google Scholar]
  • 123.Wang CL, Liang L, Fu JF. Effect of lifestyle intervention on non-alcoholic fatty liver disease in Chinese obese children. World J Gastroenterol. 2008;14:1598–1602. doi: 10.3748/wjg.14.1598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 124.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. doi: 10.1002/hep.23623. [DOI] [PubMed] [Google Scholar]
  • 125.Madan K, Batra Y, Gupta DS. Vitamin E-based therapy is effective in ameliorating transaminasemia in nonalcoholic fatty liver disease. Indian J Gastroenterol. 2005;24:251–255. [PubMed] [Google Scholar]
  • 126.Satapathy SK, Garg S, Chauhan R. Beneficial effects of tumor necrosis factor-alpha inhibition by pentoxifylline on clinical, biochemical, and metabolic parameters of patients with nonalcoholic steatohepatitis. Am J Gastroenterol. 2004;99:1946–1952. doi: 10.1111/j.1572-0241.2004.40220.x. [DOI] [PubMed] [Google Scholar]
  • 127.Satapathy SK, Sakhuja P, Malhotra V, Sharma BC, Sarin SK. Beneficial effects of pentoxifylline on hepatic steatosis, fibrosis and necroinflammation in patients with non-alcoholic steatohepatitis. J Gastroenterol Hepatol. 2007;22:634–638. doi: 10.1111/j.1440-1746.2006.04756.x. [DOI] [PubMed] [Google Scholar]
  • 128.Lee YM, Sutedja D, Wai CT. A randomized controlled pilot study of pentoxifylline in patients with non-alcoholic steatohepatitis (NASH) Hepatol Int. 2008;2:196–201. doi: 10.1007/s12072-008-9058-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 129.Uygun A, Kadayifci A, Isik AT. Metformin in the treatment of patients with non-alcoholic steatohepatitis. Aliment Pharmacol Ther. 2004;19:537–544. doi: 10.1111/j.1365-2036.2004.01888.x. [DOI] [PubMed] [Google Scholar]
  • 130.Omer Z, Cetinkalp S, Akyildiz M. Efficacy of insulin-sensitizing agents in nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol. 2010;22:18–23. doi: 10.1097/MEG.0b013e32832e2baf. [DOI] [PubMed] [Google Scholar]
  • 131.Zhu FS, Liu S, Chen XM, Huang ZG, Zhang DW. Effects of n-3 polyunsaturated fatty acids from seal oils on nonalcoholic fatty liver disease associated with hyperlipidemia. World J Gastroenterol. 2008;14:6395–6400. doi: 10.3748/wjg.14.6395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 132.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. doi: 10.1016/j.cgh.2008.08.012. [DOI] [PubMed] [Google Scholar]
  • 133.Kakizaki S, Takizawa D, Yamazaki Y. Nonalcoholic fatty liver disease in Japanese patients with severe obesity who received laparoscopic Roux-en-Y gastric bypass surgery (LRYGB) in comparison to non-Japanese patients. J Gastroenterol. 2008;43:86–92. doi: 10.1007/s00535-007-2130-0. [DOI] [PubMed] [Google Scholar]

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