A pilot study using simvastatin in the treatment of nonalcoholic steatohepatitis: A randomized placebo-controlled trial

Journal of Clinical Gastroenterology

Volumn 43, Issue 10, 2009, Pages 990-994

  Nelson, Austin ^a   Torres, Dawn M ^b   Morgan, Ana E ^b   Fincke, Christopher ^b   Harrison, Stephen A ^b  

^a WILFORD HALL MEDICAL CENTER   (United States)

^b BROOKE ARMY MEDICAL CENTER   (United States)

Author keywords

HMG CoA reductase inhibitors; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; Randomized controlled trial; Statin

Indexed keywords

ALANINE AMINOTRANSFERASE; ASPARTATE AMINOTRANSFERASE; CHOLESTEROL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; INTERLEUKIN 6; LIVER ENZYME; LOW DENSITY LIPOPROTEIN; PLACEBO; SIMVASTATIN; TUMOR NECROSIS FACTOR ALPHA; AMINOTRANSFERASE;

ABSENCE OF SIDE EFFECTS; ADULT; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; BODY MASS; CHOLESTEROL BLOOD LEVEL; CLINICAL ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DIABETES MELLITUS; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG SAFETY; FEMALE; HISTOLOGY; HUMAN; HYPERLIPIDEMIA; HYPERTENSION; INFLAMMATION; LIVER BIOPSY; LIVER FUNCTION TEST; MALE; NONALCOHOLIC FATTY LIVER; OBESITY; PILOT STUDY; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; TREATMENT OUTCOME; AGED; BIOPSY; BLOOD; FATTY LIVER; FOLLOW UP; MIDDLE AGED;

ADULT; AGED; BIOPSY; BODY MASS INDEX; DOUBLE-BLIND METHOD; FATTY LIVER; FEMALE; FOLLOW-UP STUDIES; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; HYPERLIPIDEMIAS; MALE; MIDDLE AGED; PILOT PROJECTS; SIMVASTATIN; TRANSAMINASES;

EID: 74949102941     PISSN: 01920790     EISSN: None     Source Type: Journal    
DOI: 10.1097/MCG.0b013e31819c392e     Document Type: Article

References (39)

1. Machado M, Marques-Vidal P, Cortez-Pinto H. Hepatic histology in obese patients undergoing bariatric surgery. J Hepatol. 2006;45:600-606.
2. Wanless IR, Lentz JS. Fatty liver hepatitis (steatohepatitis) and obesity: an autopsy study with analysis of risk factors. Hepatology. 1990;12:1106-1110.
3. Harrison SA, Neuschwander-Tetri BA. Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Clin Liver Dis. 2004;8:861-879.
4. Defronso RA, Ferranini E. Insulin resistance: a multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care. 1991;14:173-194.
5. Day CP, James OF. Steatohepatitis: a tale of two hits? [editorial]. Gastroenterology. 1998;114:842-845.
6. Kaplan LM. Leptin, obesity, and liver disease. Gastroenterology. 1998;115:997-1001.
7. Harrison SA, Kadakia S, Lang KA, et al.. Nonalcoholic Steatohepatitis: what we know in the new millennium. Am J Gastroenterol. 2002;97:2714-2724.
8. Adams LA, Lymp JF, Sauver JS, et al.. The natural history of nonalcoholic fatty liver. Gastroenteroloy. 2005;129: 113-121.
9. Hussein O, Grosovski M, Schlesinger S, et al.. Orlistat reverse fatty infiltration and improves hepatic fibrosis in obese patients with nonalcoholic steatohepatitis (NASH). Dig Dis Sci. 2007; 52:2512-2519. (Pubitemid 47373883)
10. Harrison SA, Torgerson S, Hayashi P, et al.. Vitamin E and C treatment improves fibrosis in patients with nonalcoholic steatohepatitis. Am J Gastroenterol. 2003;98:2485-2490.
11. Sanyal AJ, Mofrad PS, Contos MJ, et al.. A pilot study of vitamin E versus vitamin E and pioglitazone for the treatment of nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol. 2004;2:1107-1115.
12. Lindor KD, Kowdley KV, Heathcote EJ, et al.. Ursodeoxycholic acid for treatment of nonalcoholic steatohepatitis: results of a randomized trial. Hepatology. 2004;39:770-778.
13. Merat S, Malekzadeh R, Sohrabi MR, et al.. Probucol in the treatment of nonalcoholic steatohepatitis: an open-labeled study. J Clin Gastroenterol. 2003;36:266-268.
14. Deushi M, Nomura M, Kawakami A, et al.. Ezetimibe improves liver steatosis and insulin resistance in obese rat model of metabolic syndrome. FEBS Lett. 2007;581:5664-5670.
15. Yokohama S, Yoneda M, Haneda M. Therapeutic efficacy of an antiotensin II receptor antagonist in patients with nonalcoholic steatohepatitis. Hepatology. 2004;40:1222-1225.
16. Bugianesi E, Gentilcore E, Manini R, et al.. A randomized controlled trial of metformin versus vitamin E or prescriptive diet in nonalcoholic fatty liver disease. Am J Gastroenterol. 2005;100:1082-1090.
17. Belfort R, Harrison SA, Brown K, et al.. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med. 2006;355:2297-2307.
18. Ding X, Saxena NK, Lin S, et al.. Exendin-4, a glucagon-like protein-1 (GLP-1) receptor agonist, reverses hepatic steatosis in ob/ob mice. Hepatology. 2006;43:173-181.
19. Georgescu EF, Georgescu M. Therapeutic options in nonalcoholic steatohepatitis (NASH). Are all agents alike? Results of a Preliminary Study. J Gastrointestinal Liver Dis. 2007;16:39-46.
20. Gomez-Dominguez E, Gisbert JP, Moreno-Monteagudo JA, et al.. A pilot study of atorvastatin treatment in dyslipdemidic, non-alcoholic fatty liver patients. Aliment Pharmacol Ther. 2006;23:1643-1647.
21. Rallidis LO, Drakoulis CH, Parasi AI. Pravastatin in patients with nonalcoholic steatohepatitis: results of a pilot study. Letter to the Editor. Artherosclerosis. 2004;174:193-196.
22. Brunt EM, Janney CG, Di Bisceglie AM, et al.. Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol. 1999;94:2467-2474.
23. Sridevi DE, Siegel DA, Jialal IS. Simvastatin (40 mg/d), adiponectin levels, and insulin sensitivity in subjects with metabolic syndrome. Am J Cardiol. 2007;100:1397-1399.
24. Bravo AA, Sheth SG, Chopra S. Liver biopsy. N Engl J Med. 2001;344:495-500.
25. Leclercq IA, Farrell GC, Field J, et al.. CYP2E1 and CYP4A as microsomal catalyst of lipid peroxides in murine nonalcoholic steatohepatitis. J Clin Invest. 2000;105:1067-1075.
26. Kern PA, Saghizadeh M, Ong JM, et al.. The expression of tumor necrosis factor in human adipose tissue. Regulation of obesity, weight loss, and relationship to lipoprotein lipase. J Clin Invest. 1995;95:2111-2119.
27. Klover PJ, Zimmers TA, Koniaris LG, et al.. Chronic exposure to interleukin-6 causes hepatic insulin resistance in mice. Diabetes. 2003;52:2784-2789.
28. Tsochatzis E, Papatheodororidis GV, Archimandritis AJ. The evolving role of leptin and adiponectin in chronic liver diseases. Am J Gastroenterol. 2006;101:2629-2640.
29. Anania FA, Parekh S. Abnormal lipid and glucose metabolism in obesity: implications for nonalcoholic fatty liver disease. Gastroenterol. 2007;132:2191-2207.
30. Chitturi S, Farrell G, Forst L, et al.. Serum leptin in NASH correlates with hepatic steatosis but not fibrosis: a manifestation of lipotoxicity? Hepatology. 2002;36:403-409.
31. Nakao K, Nakata K, Ohtsubo N, et al.. Association between nonalcoholic fatty liver, markers of obesity, and serum leptin levels in young adults. Am J Gastroenterol. 2002;97:1796-1801.
32. Hui JM, Hodge A, Farrell GC, et al.. Beyond insulin resistance in NASH: TNF-alpha or adiponectin? Hepatology. 2004;40: 46-54.
33. Targher G, Bertolini L, Rodella S, et al.. Associations between plasma adiponectin concentrations and liver histology in patients with nonalcoholic fatty liver disease. Clin Endocrinology. 2006;64:679-683.
34. Shepherd J, Cobbe SM, Ford I, et al.. For the West of Scotland Coronary Prevention Study Group: prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med. 1995;333:1301-1307.
35. Devaraj S, Chan E, Jialal I. Direct demonstration of an antiinflammatory effect of simvastatin in subjects with the metabolic syndrome. J Clin Endocrinol Metab. 2006;91:4489-4496.
36. Zhao SP, Wu ZH. Atorvastatin reduces serum leptin concentration in hypercholesterolemic rabbits. Clin Chim Acta. 2005;360:133-140.
37. Blanco-Colio LM, Martín-Ventura JL, Gó mez-Guerrero C, et al.. Adiponectin plasma levels are increased by atorvastatin treatment in subjects at high cardiovascular risk. Eur J Pharmacol. 2008;586:259-265.
38. Chu CH, Lee JK, Lam HC, et al.. Atorvastatin does not affect insulin sensitivity and the adiponectin or leptin levels in hyperlipidemic Type 2 diabetes. J Endocrinol Invest. 2008;31:42-47.
39. Chan WB, Ko TG, Yeung VT, et al.. A comparative study of atorvastatin and simvastatin as monotherapy for mixed hyperlipidaemia in Type 2 diabetic patients. Diabetes Res Clin Prac. 2004;66:97-99.