Atorvastatin Versus Vitamin E in Treatment of Non-alcoholic Fatty Liver Disease

Summary

The purpose of the study is to compare the impact of atorvastatin 20mg qd and Vitamin E 300mg qd therapy on liver fat content in patients with type 2 diabetes associated with high LDL-C and non-alcoholic fatty liver disease.

Timeline

Start

2013-05

Primary completion

2016-12

Completion

2016-12

Publications

• Background Angulo P. Nonalcoholic fatty liver disease. N Engl J Med. 2002 Apr 18;346(16):1221-31. doi: 10.1056/NEJMra011775. No abstract available.
• Background Targher G, Bertolini L, Padovani R, Rodella S, Tessari R, Zenari L, Day C, Arcaro G. Prevalence of nonalcoholic fatty liver disease and its association with cardiovascular disease among type 2 diabetic patients. Diabetes Care. 2007 May;30(5):1212-8. doi: 10.2337/dc06-2247. Epub 2007 Feb 2.
• Background Fan JG, Zhu J, Li XJ, Chen L, Lu YS, Li L, Dai F, Li F, Chen SY. Fatty liver and the metabolic syndrome among Shanghai adults. J Gastroenterol Hepatol. 2005 Dec;20(12):1825-32. doi: 10.1111/j.1440-1746.2005.04058.x.
• Background Kotronen A, Yki-Jarvinen H. Fatty liver: a novel component of the metabolic syndrome. Arterioscler Thromb Vasc Biol. 2008 Jan;28(1):27-38. doi: 10.1161/ATVBAHA.107.147538. Epub 2007 Aug 9.
• Background Ryysy L, Hakkinen AM, Goto T, Vehkavaara S, Westerbacka J, Halavaara J, Yki-Jarvinen H. Hepatic fat content and insulin action on free fatty acids and glucose metabolism rather than insulin absorption are associated with insulin requirements during insulin therapy in type 2 diabetic patients. Diabetes. 2000 May;49(5):749-58. doi: 10.2337/diabetes.49.5.749.
• Background Seppala-Lindroos A, Vehkavaara S, Hakkinen AM, Goto T, Westerbacka J, Sovijarvi A, Halavaara J, Yki-Jarvinen H. Fat accumulation in the liver is associated with defects in insulin suppression of glucose production and serum free fatty acids independent of obesity in normal men. J Clin Endocrinol Metab. 2002 Jul;87(7):3023-8. doi: 10.1210/jcem.87.7.8638.
• Background Adiels M, Taskinen MR, Packard C, Caslake MJ, Soro-Paavonen A, Westerbacka J, Vehkavaara S, Hakkinen A, Olofsson SO, Yki-Jarvinen H, Boren J. Overproduction of large VLDL particles is driven by increased liver fat content in man. Diabetologia. 2006 Apr;49(4):755-65. doi: 10.1007/s00125-005-0125-z. Epub 2006 Feb 4.
• Background Malmstrom R, Packard CJ, Caslake M, Bedford D, Stewart P, Yki-Jarvinen H, Shepherd J, Taskinen MR. Defective regulation of triglyceride metabolism by insulin in the liver in NIDDM. Diabetologia. 1997 Apr;40(4):454-62. doi: 10.1007/s001250050700.
• Background Hanley AJ, Williams K, Festa A, Wagenknecht LE, D'Agostino RB Jr, Kempf J, Zinman B, Haffner SM; insulin resistance atherosclerosis study. Elevations in markers of liver injury and risk of type 2 diabetes: the insulin resistance atherosclerosis study. Diabetes. 2004 Oct;53(10):2623-32. doi: 10.2337/diabetes.53.10.2623.
• Background 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 Jul;129(1):113-21. doi: 10.1053/j.gastro.2005.04.014.
• Background Mehta SR, Thomas EL, Patel N, Crofton ME, McCarthy J, Eliahoo J, Morin SX, Fitzpatrick J, Durighel G, Goldstone AP, Johnston DG, Bell JD, Taylor-Robinson SD. Proton magnetic resonance spectroscopy and ultrasound for hepatic fat quantification. Hepatol Res. 2010 Apr;40(4):399-406. doi: 10.1111/j.1872-034X.2009.00620.x. Epub 2010 Mar 4.
• Background Argo CK, Loria P, Caldwell SH, Lonardo A. Statins in liver disease: a molehill, an iceberg, or neither? Hepatology. 2008 Aug;48(2):662-9. doi: 10.1002/hep.22402.
• Background Hyogo H, Tazuma S, Arihiro K, Iwamoto K, Nabeshima Y, Inoue M, Ishitobi T, Nonaka M, Chayama K. Efficacy of atorvastatin for the treatment of nonalcoholic steatohepatitis with dyslipidemia. Metabolism. 2008 Dec;57(12):1711-8. doi: 10.1016/j.metabol.2008.07.030.
• Background Kiyici M, Gulten M, Gurel S, Nak SG, Dolar E, Savci G, Adim SB, Yerci O, Memik F. Ursodeoxycholic acid and atorvastatin in the treatment of nonalcoholic steatohepatitis. Can J Gastroenterol. 2003 Dec;17(12):713-8. doi: 10.1155/2003/857869.
• Background Rallidis LS, Drakoulis CK, Parasi AS. Pravastatin in patients with nonalcoholic steatohepatitis: results of a pilot study. Atherosclerosis. 2004 May;174(1):193-6. doi: 10.1016/j.atherosclerosis.2004.01.008. No abstract available.
• Background Hatzitolios A, Savopoulos C, Lazaraki G, Sidiropoulos I, Haritanti P, Lefkopoulos A, Karagiannopoulou G, Tzioufa V, Dimitrios K. Efficacy of omega-3 fatty acids, atorvastatin and orlistat in non-alcoholic fatty liver disease with dyslipidemia. Indian J Gastroenterol. 2004 Jul-Aug;23(4):131-4.
• Background Gomez-Dominguez E, Gisbert JP, Moreno-Monteagudo JA, Garcia-Buey L, Moreno-Otero R. A pilot study of atorvastatin treatment in dyslipemid, non-alcoholic fatty liver patients. Aliment Pharmacol Ther. 2006 Jun 1;23(11):1643-7. doi: 10.1111/j.1365-2036.2006.02926.x.
• Background Antonopoulos S, Mikros S, Mylonopoulou M, Kokkoris S, Giannoulis G. Rosuvastatin as a novel treatment of non-alcoholic fatty liver disease in hyperlipidemic patients. Atherosclerosis. 2006 Jan;184(1):233-4. doi: 10.1016/j.atherosclerosis.2005.08.021. Epub 2005 Oct 5. No abstract available.
• Background Foster T, Budoff MJ, Saab S, Ahmadi N, Gordon C, Guerci AD. Atorvastatin and antioxidants for the treatment of nonalcoholic fatty liver disease: the St Francis Heart Study randomized clinical trial. Am J Gastroenterol. 2011 Jan;106(1):71-7. doi: 10.1038/ajg.2010.299. Epub 2010 Sep 14.
• Background Athyros VG, Tziomalos K, Gossios TD, Griva T, Anagnostis P, Kargiotis K, Pagourelias ED, Theocharidou E, Karagiannis A, Mikhailidis DP; GREACE Study Collaborative Group. Safety and efficacy of long-term statin treatment for cardiovascular events in patients with coronary heart disease and abnormal liver tests in the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) Study: a post-hoc analysis. Lancet. 2010 Dec 4;376(9756):1916-22. doi: 10.1016/S0140-6736(10)61272-X. Epub 2010 Nov 23.
• Background Wiesinger HA, Shah J, White A, Yoshida EM, Frohlich J, Sirrs S, Gill S, Byrne MF. Liver biochemistry abnormalities in a quaternary care lipid clinic database. Ann Hepatol. 2008 Jan-Mar;7(1):63-6.
• Background Cohen DE, Anania FA, Chalasani N; National Lipid Association Statin Safety Task Force Liver Expert Panel. An assessment of statin safety by hepatologists. Am J Cardiol. 2006 Apr 17;97(8A):77C-81C. doi: 10.1016/j.amjcard.2005.12.014. Epub 2006 Feb 3.
• Background Rougon G, Hobert O. New insights into the diversity and function of neuronal immunoglobulin superfamily molecules. Annu Rev Neurosci. 2003;26:207-38. doi: 10.1146/annurev.neuro.26.041002.131014. Epub 2003 Feb 13.
• Background Cowin GJ, Jonsson JR, Bauer JD, Ash S, Ali A, Osland EJ, Purdie DM, Clouston AD, Powell EE, Galloway GJ. Magnetic resonance imaging and spectroscopy for monitoring liver steatosis. J Magn Reson Imaging. 2008 Oct;28(4):937-45. doi: 10.1002/jmri.21542.
• Background Machann J, Thamer C, Schnoedt B, Stefan N, Haring HU, Claussen CD, Fritsche A, Schick F. Hepatic lipid accumulation in healthy subjects: a comparative study using spectral fat-selective MRI and volume-localized 1H-MR spectroscopy. Magn Reson Med. 2006 Apr;55(4):913-7. doi: 10.1002/mrm.20825.
• Background 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 Feb;288(2):E462-8. doi: 10.1152/ajpendo.00064.2004. Epub 2004 Aug 31.
• Background Liu M, Gao X, Rao SX, Wu L, Zeng MS. [Measurement of intrahepatic triglyceride stores by 1H magnetic resonance spectroscopy: study with rat models and in patients]. Zhonghua Yi Xue Za Zhi. 2008 Feb 26;88(8):531-3. Chinese.
• Background Lavine JE. Vitamin E treatment of nonalcoholic steatohepatitis in children: a pilot study. J Pediatr. 2000 Jun;136(6):734-8.
• Background 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 Nov;98(11):2485-90. doi: 10.1111/j.1572-0241.2003.08699.x.
• Background Vajro P, Mandato C, Franzese A, Ciccimarra E, Lucariello S, Savoia M, Capuano G, Migliaro F. Vitamin E treatment in pediatric obesity-related liver disease: a randomized study. J Pediatr Gastroenterol Nutr. 2004 Jan;38(1):48-55. doi: 10.1097/00005176-200401000-00012.
• Background Adams LA, Angulo P. Vitamins E and C for the treatment of NASH: duplication of results but lack of demonstration of efficacy. Am J Gastroenterol. 2003 Nov;98(11):2348-50. doi: 10.1111/j.1572-0241.2003.08695.x. No abstract available.
• Background 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; NASH CRN. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med. 2010 May 6;362(18):1675-85. doi: 10.1056/NEJMoa0907929. Epub 2010 Apr 28.
• Background Hasegawa T, Yoneda M, Nakamura K, Makino I, Terano A. Plasma transforming growth factor-beta1 level and efficacy of alpha-tocopherol in patients with non-alcoholic steatohepatitis: a pilot study. Aliment Pharmacol Ther. 2001 Oct;15(10):1667-72. doi: 10.1046/j.1365-2036.2001.01083.x.
• Background Yoshizumi T, Nakamura T, Yamane M, Islam AH, Menju M, Yamasaki K, Arai T, Kotani K, Funahashi T, Yamashita S, Matsuzawa Y. Abdominal fat: standardized technique for measurement at CT. Radiology. 1999 Apr;211(1):283-6. doi: 10.1148/radiology.211.1.r99ap15283.
• Background Hayashi T, Boyko EJ, McNeely MJ, Leonetti DL, Kahn SE, Fujimoto WY. Minimum waist and visceral fat values for identifying Japanese Americans at risk for the metabolic syndrome. Diabetes Care. 2007 Jan;30(1):120-7. doi: 10.2337/dc06-0739.
• Background Fujimoto WY, Bergstrom RW, Boyko EJ, Chen KW, Leonetti DL, Newell-Morris L, Shofer JB, Wahl PW. Visceral adiposity and incident coronary heart disease in Japanese-American men. The 10-year follow-up results of the Seattle Japanese-American Community Diabetes Study. Diabetes Care. 1999 Nov;22(11):1808-12. doi: 10.2337/diacare.22.11.1808.
• Background Ye Y, Bao Y, Hou X, Pan X, Wu H, Li H, Wang C, Tang J, Lu H, Xiang K, Jia W. Identification of waist circumference cutoffs for abdominal obesity in the Chinese population: a 7.8-year follow-up study in the Shanghai urban area. Int J Obes (Lond). 2009 Sep;33(9):1058-62. doi: 10.1038/ijo.2009.134. Epub 2009 Jul 7.

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Indications