The Fatty Acid-Bile Acid Conjugate Aramchol Reduces Liver Fat Content in Patients With Nonalcoholic Fatty Liver Disease

Clinical Gastroenterology and Hepatology

Volumn 12, Issue 12, 2014, Pages 2085-2091.e1

  Safadi, Rifaat ^a,b   Konikoff, Fred M ^c   Mahamid, Mahmud ^b   Zelber Sagi, Shira ^d,e   Halpern, Maya ^f   Gilat, Tuvia ^d,f   Oren, Ran ^a,d  

^a HADASSAH HEBREW UNIVERSITY MEDICAL CENTER   (Israel)

^b Israel   (Israel)

^c TEL AVIV UNIVERSITY   (Israel)

^d TEL AVIV SOURASKY MEDICAL CENTER   (Israel)

^e UNIVERSITY OF HAIFA   (Israel)

^f Galmed Medical Research Ltd   (Israel)

Author keywords

Cholic Acid; Clinical Trial; Lipid; NASH; Steatosis

Indexed keywords

3BETA ARACHIDYL AMIDO 7ALPHA 12ALPHA DIHYDROXY, 5BETA CHOLAN 24 OIC ACID; ADIPONECTIN; ALANINE AMINOTRANSFERASE; BILE ACID CONJUGATE; FATTY ACID; PLACEBO; UNCLASSIFIED DRUG; ARAMCHOL; CHOLIC ACID DERIVATIVE; FAT; GASTROINTESTINAL AGENT;

ADULT; AGED; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ARTICLE; ASTHENIA; BACKACHE; BODY MASS; CONSTIPATION; CONTROLLED STUDY; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG BLOOD LEVEL; DRUG EFFECT; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; FAT CONTENT; FEMALE; FOLLOW UP; HOMEOSTASIS; HUMAN; ISRAEL; MAJOR CLINICAL STUDY; MALE; METABOLIC PARAMETERS; MULTICENTER STUDY; NONALCOHOLIC FATTY LIVER; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PHASE 2 CLINICAL TRIAL; RANDOMIZED CONTROLLED TRIAL; SCORING SYSTEM; TREATMENT DURATION; UPPER ABDOMINAL PAIN; UPPER RESPIRATORY TRACT INFECTION; ADOLESCENT; BIOPSY; LIVER; MIDDLE AGED; NON-ALCOHOLIC FATTY LIVER DISEASE; PATHOLOGY; PLACENTA; PREGNANCY; TREATMENT OUTCOME; YOUNG ADULT;

ADOLESCENT; ADULT; AGED; BIOPSY; CHOLIC ACIDS; DOUBLE-BLIND METHOD; FATS; FEMALE; GASTROINTESTINAL AGENTS; HUMANS; ISRAEL; LIVER; MAGNETIC RESONANCE SPECTROSCOPY; MALE; MIDDLE AGED; NON-ALCOHOLIC FATTY LIVER DISEASE; PLACENTA; PREGNANCY; TREATMENT OUTCOME; YOUNG ADULT;

EID: 84918843434     PISSN: 15423565     EISSN: 15427714     Source Type: Journal    
DOI: 10.1016/j.cgh.2014.04.038     Document Type: Article

References (33)

1. Ratziu V., Bellentani S., Cortez-Pinto H., et al. Aposition statement on NAFLD/NASH based on the EASL 2009 special conference. JHepatol 2010, 53:372-384.
2. Chalasani N., Younossi Z., Lavine J.E., et al. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology. Gastroenterology 2012, 142:1592-1609.
3. Malinowski S.S., Byrd J.S., Bell A.M., et al. Pharmacologic therapy for nonalcoholic fatty liver disease in adults. Pharmacotherapy 2013, 33:223-242.
4. Benjamin S.M., Valdez R., Vinicor F. Diabetes prevention. NEngl J Med 2002, 346:1829-1830.
5. Lassailly G., Caiazzo R., Pattou F., et al. Bariatric surgery for curing NASH in the morbidly obese?. JHepatol 2013, 58:1249-1251.
6. Bell L.N., Wang J., Muralidharan S., et al. Relationship between adipose tissue insulin resistance and liver histology in nonalcoholic steatohepatitis: a pioglitazone versus vitamin E versus placebo for the treatment of nondiabetic patients with nonalcoholic steatohepatitis trial follow-up study. Hepatology 2012, 56:1311-1318.
7. Mahady S.E., Wong G., Craig J.C., et al. Pioglitazone and vitamin E for nonalcoholic steatohepatitis: a cost utility analysis. Hepatology 2012, 56:2172-2179.
8. Dufour J.F., Oneta C.M., Gonvers J.J., et al. Randomized placebo-controlled trial of ursodeoxycholic acid with vitamin E in nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol 2006, 4:1537-1543.
9. Schwimmer J.B., Middleton M.S., Deutsch R., et al. Aphase 2 clinical trial of metformin as a treatment for non-diabetic paediatric non-alcoholic steatohepatitis. Aliment Pharmacol Ther 2005, 21:871-879.
10. Konikoff F.M., Gilat T. Effects of fatty acid bile acid conjugates (FABACs) on biliary lithogenesis: potential consequences for non-surgical treatment of gallstones. Curr Drug Targets Immune Endocr Metabol Disord 2005, 5:171-175.
11. Dobrzyn A., Ntambi J.M. Stearoyl-CoA desaturase as a new drug target for obesity treatment. Obes Rev 2005, 6:169-174.
12. Dobrzyn P., Dobrzyn A., Miyazaki M., et al. Stearoyl-CoA desaturase 1 deficiency increases fatty acid oxidation by activating AMP-activated protein kinase in liver. Proc Natl Acad Sci U S A 2004, 101:6409-6414.
13. Leikin-Frenkel A., Goldiner I., Leikin-Gobbi D., et al. Treatment of preestablished diet-induced fatty liver by oral fatty acid-bile acid conjugates in rodents. Eur J Gastroenterol Hepatol 2008, 20:1205-1213.
14. Goldiner I., van der Velde A.E., Vandenberghe K.E., et al. ABCA1-dependent but apoA-I-independent cholesterol efflux mediated by fatty acid-bile acid conjugates (FABACs). Biochem J 2006, 396:529-536.
15. Leikin-Frenkel A., Gonen A., Shaish A., et al. Fatty acid bile acid conjugate inhibits hepatic stearoyl coenzyme A desaturase and is non-atherogenic. Arch Med Res 2010, 41:397-404.
16. MacDonald M.L., van Eck M., Hildebrand R.B., et al. Despite antiatherogenic metabolic characteristics, SCD1-deficient mice have increased inflammation and atherosclerosis. Arterioscler Thromb Vasc Biol 2009, 29:341-347.
17. Zhang Z., Dales N.A., Winther M.D. Opportunities and challenges in developing stearoyl-coenzyme A desaturase-1 inhibitors as novel therapeutics for human disease. JMed Chem 2013 Dec20, Epub ahead of print.
18. Fischbach F., Bruhn H. Assessment of invivo 1H magnetic resonance spectroscopy in the liver: a review. Liver Int 2008, 28:297-307.
19. Kang G.H., Cruite I., Shiehmorteza M., et al. Reproducibility of MRI-determined proton density fat fraction across two different MR scanner platforms. JMagn Reson Imaging 2011, 34:928-934.
20. Szczepaniak L.S., Nurenberg P., Leonard D., et al. Magnetic resonance spectroscopy to measure hepatic triglyceride content: prevalence of hepatic steatosis in the general population. Am J Physiol Endocrinol Metab 2005, 288:E462-E468.
21. Villanova N., Moscatiello S., Ramilli S., et al. Endothelial dysfunction and cardiovascular risk profile in nonalcoholic fatty liver disease. Hepatology 2005, 42:473-480.
22. Giannotti G., Landmesser U. Endothelial dysfunction as an early sign of atherosclerosis. Herz 2007, 32:568-572.
23. Brevetti G., Silvestro A., Schiano V., et al. Endothelial dysfunction and cardiovascular risk prediction in peripheral arterial disease: additive value of flow-mediated dilation to ankle-brachial pressure index. Circulation 2003, 108:2093-2098.
24. Belfort R., Harrison S.A., Brown K., et al. Aplacebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. NEngl J Med 2006, 355:2297-2307.
25. Mathurin P., Hollebecque A., Arnalsteen L., et al. Prospective study of the long-term effects of bariatric surgery on liver injury in patients without advanced disease. Gastroenterology 2009, 137:532-540.
26. Nobili V., Manco M., Devito R., et al. Lifestyle intervention and antioxidant therapy in children with nonalcoholic fatty liver disease: a randomized, controlled trial. Hepatology 2008, 48:119-128.
27. Dixon J.B., Bhathal P.S., Hughes N.R., et al. Nonalcoholic fatty liver disease: improvement in liver histological analysis with weight loss. Hepatology 2004, 39:1647-1654.
28. Krawczyk M., Bonfrate L., Portincasa P. Nonalcoholic fatty liver disease. Best Pract Res Clin Gastroenterol 2010, 24:695-708.
29. Lonardo A., Bellentani S., Ratziu V., et al. Insulin resistance in nonalcoholic steatohepatitis: necessary but not sufficient-death of a dogma from analysis of therapeutic studies?. Expert Rev Gastroenterol Hepatol 2011, 5:279-289.
30. Lonardo A., Lombardini S., Ricchi M., et al. Review article: hepatic steatosis and insulin resistance. Aliment Pharmacol Ther 2005, 22(Suppl 2):64-70.
31. Tilg H., Moschen A.R. Evolution of inflammation in nonalcoholic fatty liver disease: the multiple parallel hits hypothesis. Hepatology 2010, 52:1836-1846.
32. Gaggini M., Morelli M., Buzzigoli E., et al. Non-alcoholic fatty liver disease (NAFLD) and its connection with insulin resistance, dyslipidemia, atherosclerosis and coronary heart disease. Nutrients 2013, 5:1544-1560.
33. Rabin K.R., Kamari Y., Avni I., et al. Adiponectin: linking the metabolic syndrome to its cardiovascular consequences. Expert Rev Cardiovasc Ther 2005, 3:465-471.