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. 1991 Sep;32(9):1061–1065. doi: 10.1136/gut.32.9.1061

Ursodeoxycholic acid in chronic liver disease.

J S de Caestecker 1, R P Jazrawi 1, M L Petroni 1, T C Northfield 1
PMCID: PMC1379051  PMID: 1916492

Abstract

The hydrophilic bile acid ursodeoxycholic acid has recently been shown to reduce biochemical markers of both cholestasis and hepatocellular damage in patients with chronic liver diseases. The most compelling evidence available is for chronic cholestatic liver diseases, in particular primary biliary cirrhosis, primary sclerosing cholangitis, and cholestasis associated with cystic fibrosis. The effects may be less beneficial in patients with advanced liver disease from these conditions. Data from placebo controlled trials are now available in support of earlier uncontrolled observations, but it is not yet clear whether short term benefit results in an improvement in longterm prognosis. The mechanism of action of the compound seems to reside in its displacement of toxic hydrophobic bile acids from both the bile acid pool and hepatocellular membranes. There may be an independent effect on bile flow, which could be of particular importance in cystic fibrosis, and possibly an effect on the immune system. Ursodeoxycholic acid should now be regarded as occupying a central place in the medical management of chronic cholestatic liver diseases, in particular primary biliary cirrhosis, because it improves cholestasis and reduces hepatocellular damage and it is not toxic. Research should now be targeted on whether treatment with ursodeoxycholic acid, initiated early in cholestatic liver conditions, improves the long-term outcome.

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Selected References

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  1. Balasubramaniam K., Grambsch P. M., Wiesner R. H., Lindor K. D., Dickson E. R. Diminished survival in asymptomatic primary biliary cirrhosis. A prospective study. Gastroenterology. 1990 Jun;98(6):1567–1571. doi: 10.1016/0016-5085(90)91091-j. [DOI] [PubMed] [Google Scholar]
  2. Bateson M. C., Ross P. E., Diffey B. L. Ursodeoxycholic acid in primary biliary cirrhosis. Lancet. 1989 Apr 22;1(8643):898–899. doi: 10.1016/s0140-6736(89)92888-2. [DOI] [PubMed] [Google Scholar]
  3. Batta A. K., Salen G., Arora R., Shefer S., Tint G. S., Abroon J., Eskreis D., Katz S. Effect of ursodeoxycholic acid on bile acid metabolism in primary biliary cirrhosis. Hepatology. 1989 Oct;10(4):414–419. doi: 10.1002/hep.1840100404. [DOI] [PubMed] [Google Scholar]
  4. Bellentani S., Tabarroni G., Barchi T., Ferretti I., Fratti N., Villa E., Manenti F. Effect of ursodeoxycholic acid treatment on alanine aminotransferase and gamma-glutamyltranspeptidase serum levels in patients with hypertransaminasemia. Results from a double-blind controlled trial. J Hepatol. 1989 Jan;8(1):7–12. doi: 10.1016/0168-8278(89)90155-4. [DOI] [PubMed] [Google Scholar]
  5. Bircher J. Treatment of patients with benign recurrent intrahepatic cholestasis. Hepatology. 1989 Dec;10(6):1030–1032. doi: 10.1002/hep.1840100632. [DOI] [PubMed] [Google Scholar]
  6. Calmus Y., Gane P., Rouger P., Poupon R. Hepatic expression of class I and class II major histocompatibility complex molecules in primary biliary cirrhosis: effect of ursodeoxycholic acid. Hepatology. 1990 Jan;11(1):12–15. doi: 10.1002/hep.1840110104. [DOI] [PubMed] [Google Scholar]
  7. Chazouillères O., Poupon R., Capron J. P., Metman E. H., Dhumeaux D., Amouretti M., Couzigou P., Labayle D., Trinchet J. C. Ursodeoxycholic acid for primary sclerosing cholangitis. J Hepatol. 1990 Jul;11(1):120–123. doi: 10.1016/0168-8278(90)90281-u. [DOI] [PubMed] [Google Scholar]
  8. Chretien Y., Poupon R., Gherardt M. F., Chazouilleres O., Labbe D., Myara A., Trivin F. Bile acid glycine and taurine conjugates in serum of patients with primary biliary cirrhosis: effect of ursodeoxycholic treatment. Gut. 1989 Aug;30(8):1110–1115. doi: 10.1136/gut.30.8.1110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cotting J., Lentze M. J., Reichen J. Effects of ursodeoxycholic acid treatment on nutrition and liver function in patients with cystic fibrosis and longstanding cholestasis. Gut. 1990 Aug;31(8):918–921. doi: 10.1136/gut.31.8.918. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Graham J. M., Northfield T. C. Solubilization of lipids from hamster bile-canalicular and contiguous membranes and from human erythrocyte membranes by conjugated bile salts. Biochem J. 1987 Mar 15;242(3):825–834. doi: 10.1042/bj2420825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hofmann A. F., Popper H. Ursodeoxycholic acid for primary biliary cirrhosis. Lancet. 1987 Aug 15;2(8555):398–399. doi: 10.1016/s0140-6736(87)92421-4. [DOI] [PubMed] [Google Scholar]
  12. Kaplan M. M. Medical treatment of primary biliary cirrhosis. Semin Liver Dis. 1989 May;9(2):138–143. doi: 10.1055/s-2008-1040505. [DOI] [PubMed] [Google Scholar]
  13. Kitani K., Kanai S. Interactions between different bile salts in the biliary excretion of the rat. Res Commun Chem Pathol Pharmacol. 1983 Jan;39(1):139–152. [PubMed] [Google Scholar]
  14. Kitani K., Kanai S. Tauroursodeoxycholate prevents taurocholate induced cholestasis. Life Sci. 1982 Feb 7;30(6):515–523. doi: 10.1016/0024-3205(82)90264-8. [DOI] [PubMed] [Google Scholar]
  15. Leuschner U., Fischer H., Kurtz W., Güldütuna S., Hübner K., Hellstern A., Gatzen M., Leuschner M. Ursodeoxycholic acid in primary biliary cirrhosis: results of a controlled double-blind trial. Gastroenterology. 1989 Nov;97(5):1268–1274. doi: 10.1016/0016-5085(89)91698-3. [DOI] [PubMed] [Google Scholar]
  16. Leuschner U., Leuschner M., Sieratzki J., Kurtz W., Hübner K. Gallstone dissolution with ursodeoxycholic acid in patients with chronic active hepatitis and two years follow-up. A pilot study. Dig Dis Sci. 1985 Jul;30(7):642–649. doi: 10.1007/BF01308413. [DOI] [PubMed] [Google Scholar]
  17. Matsuzaki Y., Tanaka N., Osuga T., Aikawa T., Shoda J., Doi M., Nakano M. Improvement of biliary enzyme levels and itching as a result of long-term administration of ursodeoxycholic acid in primary biliary cirrhosis. Am J Gastroenterol. 1990 Jan;85(1):15–23. [PubMed] [Google Scholar]
  18. Nittono H., Tokita A., Hayashi M., Nakatsu N., Obinata K., Watanabe T., Yamashiro Y., Yabuta K., Miyano T. Ursodeoxycholic acid in biliary atresia. Lancet. 1988 Mar 5;1(8584):528–528. doi: 10.1016/s0140-6736(88)91313-x. [DOI] [PubMed] [Google Scholar]
  19. Nittono H., Tokita A., Hayashi M., Watanabe T., Obinata K., Nakatsu N., Miyano T. Ursodeoxycholic acid therapy in the treatment of biliary atresia. Biomed Pharmacother. 1989;43(1):37–41. doi: 10.1016/0753-3322(89)90189-3. [DOI] [PubMed] [Google Scholar]
  20. Podda M., Ghezzi C., Battezzati P. M., Bertolini E., Crosignani A., Petroni M. L., Zuin M. Effect of different doses of ursodeoxycholic acid in chronic liver disease. Dig Dis Sci. 1989 Dec;34(12 Suppl):59S–65S. doi: 10.1007/BF01536665. [DOI] [PubMed] [Google Scholar]
  21. Poupon R. E., Eschwège E., Poupon R. Ursodeoxycholic acid for the treatment of primary biliary cirrhosis. Interim analysis of a double-blind multicentre randomized trial. The UDCA-PBC Study Group. J Hepatol. 1990 Jul;11(1):16–21. doi: 10.1016/0168-8278(90)90265-s. [DOI] [PubMed] [Google Scholar]
  22. Poupon R., Chrétien Y., Poupon R. E., Ballet F., Calmus Y., Darnis F. Is ursodeoxycholic acid an effective treatment for primary biliary cirrhosis? Lancet. 1987 Apr 11;1(8537):834–836. doi: 10.1016/s0140-6736(87)91610-2. [DOI] [PubMed] [Google Scholar]
  23. Stiehl A., Rudolph G., Raedsch R., Möller B., Hopf U., Lotterer E., Bircher J., Fölsch U., Klaus J., Endele R. Ursodeoxycholic acid-induced changes of plasma and urinary bile acids in patients with primary biliary cirrhosis. Hepatology. 1990 Sep;12(3 Pt 1):492–497. doi: 10.1002/hep.1840120308. [DOI] [PubMed] [Google Scholar]
  24. Thompson J. N., Cohen J., Blenkharn J. I., McConnell J. S., Barr J., Blumgart L. H. A randomized clinical trial of oral ursodeoxycholic acid in obstructive jaundice. Br J Surg. 1986 Aug;73(8):634–636. doi: 10.1002/bjs.1800730819. [DOI] [PubMed] [Google Scholar]
  25. Triger D. R. Update on primary biliary cirrhosis. Dig Dis. 1990;8(2):61–70. doi: 10.1159/000171240. [DOI] [PubMed] [Google Scholar]
  26. Ullrich D., Rating D., Schröter W., Hanefeld F., Bircher J. Treatment with ursodeoxycholic acid renders children with biliary atresia suitable for liver transplantation. Lancet. 1987 Dec 5;2(8571):1324–1324. doi: 10.1016/s0140-6736(87)91208-6. [DOI] [PubMed] [Google Scholar]
  27. Vogel W., Kathrein H., Judmaier G., Braunsteiner H. Deterioration of primary biliary cirrhosis during treatment with ursodeoxycholic acid. Lancet. 1988 May 21;1(8595):1163–1163. doi: 10.1016/s0140-6736(88)91974-5. [DOI] [PubMed] [Google Scholar]

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