Ursodeoxycholic acid: A therapeutic niche in an internist’s practice

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Abstract

The paper shows more than 40 years’ experience with ursodeoxycholic acid (UDCA) used as a drug; during this period it has demonstrated its rather high clinical efficacy. Due to the range of its inherent pleiotropic (choleretic, cytoprotective, immunomodulatory, antiapoptotic, hypocholesterolemic, and litholytic) properties, UDCA has a broad spectrum of therapeutic activity. The paper considers the issues associated with the mechanism of action and with the clinical effects of this bile acid. It gives the results of the most important randomized controlled trials determining currently the evidence base for the efficiency and safety of using UDCA in the clinical picture of visceral diseases.

About the authors

O M Drapkina

E L Bueverova

References

  1. Kotb M.A. Molecular mechanisms of ursodeoxycholic Acid toxicity & side effects: ursodeoxycholic Acid freezes regeneration & induces hibernation mode. Int J Mol Sci 2012; 13 (7): 8882—8914.
  2. Trauner M., Graziadei I.W. Review article: mechanisms of action and therapeutic applications of ursodeoxycholic acid in chronic liver diseases. Aliment Pharmacol Ther 1999; 13 (8): 979—996.
  3. Матвеев А.В. Гепатопротекторы. Анализ международных исследований по препаратам группы лекарств для печени. Симферополь: ИТ «АРИАЛ», 2013. 384.
  4. Hagey L.R., Crombie D.L., Espinosa E. Carey M.C., Igimi H., Hofmann A.F. Ursodeoxycholic acid in the Ursidae: biliary bile acids of bears, pandas, and related carnivores. J Lipid Res 1993; 34 (11): 1911—1917.
  5. Lim A.G., Jazrawi R.P., Northfield T.C. The ursodeoxycholic acid story in primary biliary cirrhosis. Gut 1995; 37 (3): 301—304.
  6. Makino I., Tanaka H. From a choleretic to an immunomodulator: historical review of ursodeoxycholic acid as a medicament. J Gastroenterol Hepatol 1998; 13 (6): 659—664.
  7. Kanazawa T., Shimazake A., Sato T., Hoshino T. Synthesis of ursodeoxycholic acid and its conjugated bile acid. Proc Jpn Acod 1954; 30: 391—394.
  8. Danzinger R.G., Hofmann A.F., Schoenfield L.J., Thistle J.L. Dissolution of cholesterol gallstones by chenodeoxycholic acid. N Engl J Med 1972; 286 (1): 1—8.
  9. Leuschner U., Leuschner M., Sieratzki J., Kurtz W., Hubner K. Gallstone dissolution with ursodeoxycholic acid in patients with chronic active hepatitis and two years follow-up. A pilot study. Dig Dis Sci 1985; 30 (7): 642—649.
  10. Fischer M.M., Paradine M.E. Influence of ursodeoxycholic acid (UDCA) on biochemical parameters in cholestatic liver disease. Gastroenterology 1986; (90): 1725.
  11. Poupon R., Chretien Y., Poupon R.E., Ballet F., Calmus Y., Darnis F. Is ursodeoxycholic acid an effective treatment for primary biliary cirrhosis? Lancet 1987; 1 (8537): 834—836.
  12. Tsubakio K., Kiriyama K., Matsushima N., Taniguchi M., Shizusawa T., Katoh T., Manabe N., Yabu M., Kanayama Y., Himeno S. Autoimmune pancreatitis successfully treated with ursodeoxycholic acid. Intern Med 2002; 41 (12): 1142—1146.
  13. Tarao K., Fujiyama S. Ohkawa S., Miyakawa K., Tamai S., Hirokawa S., Masaki T., Tanaka K. Ursodiol use is possibly associated with lower incidence of hepatocellular carcinoma in hepatitis C virus-associated liver cirrhosis. Cancer Epidemiol Biomarkers Prev 2005; 14 (1): 164—169.
  14. Hempfling W., Dilger K., Beuers U. Systematic review: ursodeoxycholic acid — adverse effects and drug interactions. Aliment Pharmacol Ther 2003; 18 (10): 963—972.
  15. Stiehl A., Raedsch R., Rudolph G. Ileal excretion of bile acids: comparison with biliary bile composition and effect of ursodeoxycholic acid treatment. Gastroenterology 1988; 94: 1201—1206.
  16. Ceryak S., Bouscarel B., Fromm H. Comparative binding of bile acids to serum lipoproteins and albumin. J Lipid Res 1993; 34 (10): 1661—1674.
  17. Hofmann A.F. Pharmacology of ursodeoxycholic acid, an enterohepatic drug. Scand J Gastroenterol Suppl. 1994; 204: 1—15.
  18. Lazaridis K.N., Gores G.J., Lindor K.D. Ursodeoxycholic acid «mechanisms of action and clinical use in hepatobiliary disorders». J Hepatol 2001; 35 (1): 134—46.
  19. Angulo P. Use of ursodeoxycholic acid in patients with liver disease. Curr Gastroenterol Rep 2002; 4 (1): 37—44.
  20. Stiehl A.,Rudolph G., Raedsch R., Möller B., Hopf U., Lotterer E., Bircher J., Fölsch U., Klaus J., Endele R. et al. Ursodeoxycholic acid-induced changes of plasma and urinary bile acids in patients with primary biliary cirrhosis. Hepatology 1990;12: 492—497.
  21. Batta A.K., Arora R., Salen G., Tint G.S., Eskreis D., Katz S. Characterization of serum an durinary bile acids in patients with primary biliary cirrhosis by gasliquid chromatography-massspectrometry: effect of ursodeoxycholic acid treatment. J Lipid Res 1989; 30 (12): 1953—1962.
  22. Marteau P., Chazouilléres O., Myara A., Jian R., Rambaud J.C., Poupon R. Effect of chronic administration of ursodeoxycholic acid on the ileal absorption of endogenous bile acids in man. Hepatology 1990; 12 (5): 1206—1208.
  23. Stiehl A., Raedsch R., Rudolph G. Acute effects of ursodeoxycholic and chenodeoxycholic acid on the small intestinal absorption of bile acids. Gastroenterology 1990; 98 (2): 424—428.
  24. Heuman D.M., Bajaj R. Ursodeoxycholate conjugates protect against disruption of cholesterol-rich membranes by bile salts. Gastroenterology 1994; 106 (5): 1333—1341.
  25. Beuers U., Spengler U., Zwiebel F.M., Pauletzki J., Fischer S., Paumgartner G. Effect of ursodeoxycholic acid on the kinetics of the major hydrophobic bile acids in health and in chronic cholestatic liver disease. Hepatology 1992; 15 (4): 603—608.
  26. Portincasa P. Ciaula A.D., Bonfrate L., Wang D.Q. Therapy of gallstone disease: What it was, what it is, what it will be. World J Gastrointest Pharmacol Ther 2012; 3 (2): 7—20.
  27. May G.R., Sutherland L.R., Shaffer E.A. Efficacy of bile acid therapy for gallstone dissolution: a meta-analysis of randomized trials. Aliment Pharmacol Ther 1993; 7 (2): 139—148.
  28. Simko V., Michael S., Prego V. Ursodeoxycholic therapy in chronic liver disease: a meta-analysis in primary biliary cirrhosis and in chronic hepatitis. Am J Gastroenterol 1994; 89 (3): 392—298.
  29. Shi J., Wu C., Lin Y., Chen Y.X., Zhu L., Xie W.F. Long-term effects of mild-dose ursodeoxycholic acid in primary biliary cirrhosis: a meta-analysis of randomized controlled trials. Am J Gastroenterol 2006; 101 (7): 1529—1538.
  30. Gong Y., Huang Z.B., Christensen E., Gluud C. Ursodeoxycholic acid for primary biliary cirrhosis. Cochrane Database Syst Rev 2008; (3): CD000551.
  31. Hirschfield G.M., Invernizzi P. Progress in the genetics of primary biliary cirrhosis. Semin Liver Dis 2011; 31 (2): 147—156.
  32. Ishibashi H. Komori A., Shimoda S., Ambrosini Y.M., Gershwin M.E., Nakamura M. Risk factors and prediction of long-term outcome in primary biliary cirrhosis. Intern Med 2011; 50 (1): 1—10.
  33. O’Brien C.B., Senior J.R., Arora-Mirchandani R., Batta A.K., Salen G. Ursodeoxycholic acid for the treatment of primary sclerosing cholangitis: a 30-month pilot study. Hepatology 1991; 14 (5): 838—847.
  34. Beuers U., Spengler U., Kruis W., Aydemir U., Wiebecke B., Heldwein W., Weinzierl M., Pape G.R., Sauerbruch T., Paumgartner G. Ursodeoxycholic acid for treatment of primary sclerosing cholangitis: a placebo-controlled trial. Hepatology 1992; 16 (3): 707—714.
  35. Mitchell S.A., Bansi D.S., Hunt N., Von Bergmann K., Fleming K.A., Chapman R.W. A preliminary trial of high-dose ursodeoxycholic acid in primary sclerosing cholangitis. Gastroenterology 2001; 121 (4): 900—907.
  36. Lindor K.D., Kowdley K.V., Luketic V.A., Harrison M.E., McCashland T., Befeler A.S., Harnois D., Jorgensen R., Petz J., Keach J., Mooney J., Sargeant C., Braaten J., Bernard T., King D., Miceli E., Schmoll J., Hoskin T., Thapa P., Enders F. High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis. Hepatology 2009; 50 (3): 808—814.
  37. Shi J., Li Z Zeng X., Lin Y., Xie W.F. Ursodeoxycholic acid in primary sclerosing cholangitis: meta-analysis of randomized controlled trials. Hepatol Res 2009; 39 (9): 865—873.
  38. Poropat G., Giljaca V., Stimac D., Gluud C. Bile acids for primary sclerosing cholangitis. Cochrane Database Syst Rev 2011; 1: CD003626.
  39. Plevris J.N., Hayes P.C., Bouchier I. Ursodeoxycholic acid in the treatment of alcoholic liver disease. Eur J Gastroenterol Hepatol 1991; (3): 653—656.
  40. Bettini R., Gorini M. Use of ursodeoxycholic acid combined with silymarin in the treatment of chronic ethyl-toxic hepatopathy. Clin Ter 2002; 153 (5): 305—307.
  41. Маев И.В., Кучерявый Ю.А., Морозов С.В, Стукова Н.Ю. Влияние препаратов урсодезоксихолевой кислоты на биохимические показатели крови и результаты эластографии печени у пациентов с алкогольным циррозом печени. Клин перспективы гастроэнтерологии, гепатологии 2010; 4: 43—48.
  42. Sato S., Miyake T., Tobita H., Oshima N., Ishine J., Hanaoka T., Amano Y., Kinoshita Y. A dose-up of ursodeoxycholic acid decreases transaminases in hepatitis C patients. World J Gastroenterol 2009; 15 (22): 2782—2786.
  43. Bertolotti D.M., Morselli-Labate A.M., Rusticali A.G., Loria P., Carulli N. Ursodeoxycholic Acid Improves Liver Tests in Chronic Hepatitis. Clin Drug Investig 1999; 17 (6): 425—434.
  44. Omata M., Yoshida H., Yoshida H., Toyota J., Tomita E., Nishiguchi S., Hayashi N., Iino S., Makino I., Okita K., Toda G., Tanikawa K., Kumada H.; Japanese C-Viral Hepatitis Network. A large-scale, multicentre, double-blind trial of ursodeoxycholic acid in patients with chronic hepatitis C. Gut 2007; 56: 1747—1753.
  45. Лапина Т.Л., Картавенко И.М. Урсодезоксихолевая кислота: влияние на слизистую оболочку верхних отделов желудочно-кишечного тракта. Рос журн гастроэнтерол, гепатол и колопроктол 2007; 6: 51—57.
  46. Grand’Maison S., Durand M., Mahone M. The effects of ursodeoxycholic acid treatment for intrahepatic cholestasis of pregnancy on maternal and fetal outcomes: a meta-analysis including non-randomized studies. J Obstet Gynaecol Can 2014; 36 (7):632—641.
  47. Poropat G., Giljaca V., Stimac D., Gluud C. Bile acids for liver-transplanted patients. Cochrane Database Syst Rev 2010; (3): CD005442.
  48. Testoni Р.А. Acute recurrent pancreatitis: Etiopathogenesis, diagnosis and treatment. World J Gastroenterol 2014; 20 (45): 16891—16901.
  49. Alberts D.S., Martínez M.E., Hess L.M., Einspahr J.G., Green S.B., Bhattacharyya A.K., Guillen J., Krutzsch M., Batta A.K., Salen G., Fales L., Koonce K., Parish D., Clouser M., Roe D., Lance P.; Phoenix and Tucson Gastroenterologist Networks. Phase III trial of ursodeoxycholic acid to prevent colorectal adenoma recurrence. J Natl Cancer Inst 2005; 97 (11): 846—853.
  50. Day C.P., De Minicis S., Svegliati-Baroni G. From NAFLD to NASH and HCC: pathogenetic mechanisms and therapeutic insights. Curr Pharm Des 2013; 19 (29): 5239—5249.
  51. Ekstedt M., Franzén L.E., Mathiesen U.L., Holmqvist M., Bodemar G., Kechagias S. Statins in non-alcoholic fatty liver disease and chronically elevated liver enzymes: a histopathological follow-up study. J Hepatol 2007; 47 (1): 135—141.
  52. Lonardo A., Sookoian S., Chonchol M., Loria P., Targher G. Cardiovascular and systemic risk in nonalcoholic fatty liver disease — atherosclerosis as a major player in the natural course of NAFLD. Curr Pharm Des 2013; 19 (29): 5177—5192.
  53. Siebler J., Gall P. Treatment of nonalcoholic fatty liver disease. World J Gastroenterol 2006; 12 (14): 2161—2167.
  54. Буеверов А.О. Возможности клинического применения урсодезоксихолевой кислоты. Consilium Medicum 2005; 7 (6): 18—22.
  55. Ratziu V., Zelber-Sagi S. Pharmacologic therapy of non-alcoholic steatohepatitis. Clin Liver Dis 2009; 13 (4): 667—688.
  56. Leuschner U.F., Lindenthal B., Herrmann G., Arnold J.C., Rössle M., Cordes H.J., Zeuzem S., Hein J., Berg T.; NASH Study Group. High-dose ursodeoxycholic acid therapy for nonalcoholic steatohepatitis: a double-blind, randomized, placebo-controlledtrial. Hepatology 2010; 52 (2): 472—479.
  57. Xiang Z., Chen Y.P., Ma K.F. The role of ursodeoxycholic acid in non-alcoholic steatohepatitis: a systematic review. BMC Gastroenterol 2013; 13: 140.
  58. Cabezas Gelabert R. Effect of ursodeoxycholic acid combined with statins in hypercholesterolemia treatment: a prospective clinical trial. Rev Clin Esp 2004; 204 (12): 632—635.
  59. Буеверова Е.Л. Нарушения липидного обмена у больных с метаболическим синдромом: Дис. ... канд. мед. наук. М., 2009. Доступно по: http://www.dissercat.com/content/narusheniya-lipidnogo-obmena-u-bolnykh-s-metabolicheskim-sindromom. Ссылка активна 13.02.2015.
  60. Корнеева О.Н., Драпкина О.М. Комбинация урсодезоксихолевой кислоты и аторвастатина: вопросы межлекарственного взаимодействия в лечении пациентов с ожирением и сопутствующей патологией печени. Рос мед вести 2012; 1: 29—33.
  61. Драпкина О.М., Авилова А.Г. Статины и неалкогольная жировая болезнь печени. Атеросклероз и дислипидемии 2014; 1: 31—36.
  62. Драпкина О.М., Деева Т.А., Волкова Н.П., Ивашкин В.Т. Современные подходы к диагностике и лечению НАЖБ. Тер архив 2014; 10: 116—123.
  63. Claudel T., Staels B., Kuipers F. The Farnesoid X receptor: a molecular link between bile acid and lipid and glucose metabolism. Arterioscler Thromb Vasc Biol 2005; 25 (10): 2020—2030.
  64. Ивашкин В.Т. Ядерные рецепторы и патология печени. Рос журн гастроэнтерол, гепатол и колопроктол 2010; 4: 7—15.

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