Ursodeoxycholic acid in cholestasis: Potential mechanisms of action and therapeutic applications
1998; Lippincott Williams & Wilkins; Volume: 28; Issue: 6 Linguagem: Inglês
10.1002/hep.510280601
ISSN1527-3350
AutoresUlrich Beuers, James L. Boyer, Gustav Paumgartner,
Tópico(s)Pediatric Hepatobiliary Diseases and Treatments
ResumoHepatologyVolume 28, Issue 6 p. 1449-1453 Concise ReviewFree Access Ursodeoxycholic acid in cholestasis: Potential mechanisms of action and therapeutic applications Ulrich Beuers M.D., Corresponding Author Ulrich Beuers M.D. [email protected] Department of Medicine II, Klinikum Grosshadern, University of Munich, Munich, GermanyDepartment of Medicine II, Klinikum Grosshadern, University of Munich, 81377 Munich, Germany. Fax: 49-89-7095-8887===Search for more papers by this authorJames L. Boyer, James L. Boyer Liver Center, Yale University School of Medicine, New Haven, CTSearch for more papers by this authorGustav Paumgartner, Gustav Paumgartner Department of Medicine II, Klinikum Grosshadern, University of Munich, Munich, GermanySearch for more papers by this author Ulrich Beuers M.D., Corresponding Author Ulrich Beuers M.D. [email protected] Department of Medicine II, Klinikum Grosshadern, University of Munich, Munich, GermanyDepartment of Medicine II, Klinikum Grosshadern, University of Munich, 81377 Munich, Germany. Fax: 49-89-7095-8887===Search for more papers by this authorJames L. Boyer, James L. Boyer Liver Center, Yale University School of Medicine, New Haven, CTSearch for more papers by this authorGustav Paumgartner, Gustav Paumgartner Department of Medicine II, Klinikum Grosshadern, University of Munich, Munich, GermanySearch for more papers by this author First published: 30 December 2003 https://doi.org/10.1002/hep.510280601Citations: 152AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL References 1 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: 642– 649. 2 Poupon R, Poupon RE, Calmus Y, Chretien Y, Ballet F, Darnis F. Is ursodeoxycholic acid an effective treatment for primary biliary cirrhosis? Lancet 1987; 1: 834– 836.MEDLINE 3 Leuschner U, Fischer H, Kurtz W, Güldütuna S, Hubner K, Hellstern A, Gatzen M, et al. Ursodeoxycholic acid in primary biliary cirrhosis: results of a controlled double-blind trial. Gastroenterology 1989; 97: 1268– 1274.MEDLINE 4 Mijayi K, Akiyama T, Ito M, Urakawa T, Shimaji Y. The effect of ursodeoxycholic acid on liver functions in patients with chronic liver disease. A double blind study in one institution and the study on the effect on hepatic blood flow. Rinsho to Kenkyu 1976; 53: 1395– 1403. 5 Yamanaka M, Oto M, Obata H, Shimizu M, Sugata F, Hatta Y, Dohi Y, et al. The examination of the therapeutic efficacy of ursodeoxycholic acid on chronic hepatitis. A double blind study. Shindan to Chiryo 1976; 64: 2150– 2157. 6 Poupon RE, Lindor KD, Cauch-Dudek K, Dickson ER, Poupon R, Heathcote EJ. Combined analysis of randomized controlled trials of ursodeoxycholic acid in primary biliary cirrhosis. Gastroenterology 1997; 113: 884– 890.MEDLINE 7 Shoda M. Über die Ursodesoxycholsäure aus Bärengallen und ihre physiologische Wirkung. J Biochem 1927; 7: 505– 510. 8 Kitani K. Hepatoprotective effect of ursodeoxycholate in experimental animals. In: G Paumgartner, A Stiehl, L Barbara, E Roda, eds. Strategies For the Treatment of Hepatobiliary Diseases. Lancaster: Kluwer. 1990; 43– 56. 9 Hofmann AF. Pharmacology of ursodeoxycholic acid, an enterohepatic drug. Scand J Gastroenterol 1994; 204(Suppl): 1– 15. 10 Stiehl A, Raedsch R, Rudolph G. Acute effects of ursodeoxycholic and chenodeoxycholic acid on the small intestinal absorption of bile acids. Gastroenterology 1990; 98: 424– 428.MEDLINE 11 Marteau P, Chazouilleres O, Myara A, Jian R, Rambaud JC, Poupon R. Effect of chronic administration of ursodeoxycholic acid on the ileal absorption of endogenous bile acids in man. Hepatology 1990; 12: 1206– 1208.MEDLINE 12 Eusufzai S, Ericsson S, Cederlund T, Einarsson K, Angelin B. Effect of ursodeoxycholic acid treatment on ileal absorption of bile acids in man as determined by the SeHCAT test. Gut 1991; 32: 1044– 1048.MEDLINE 13 Beuers U, Spengler U, Zwiebel FM, Pauletzki J, Fischer S, Paumgartner G. Effect of ursodeoxycholic acid on kinetics of major hydrophobic bile acids in health and in chronic cholestatic liver disease. Hepatology 1992; 15: 603– 608.MEDLINE 14 Rudolph G, Endele R, Senn M, Stiehl A. Effect of ursodeoxycholic acid on the kinetics of cholic acid and chenodeoxycholic acid in patients with primary sclerosing cholangitis. Hepatology 1993; 17: 1028– 1032.MEDLINE 15 Mazzella G, Parini P, Bazzoli F, Villanova N, Festi D, Aldini R, Roda A, et al. Ursodeoxycholic acid administration on bile acid metabolism in patients with early stages of primary biliary cirrhosis. Dig Dis Sci 1993; 38: 896– 902.MEDLINE 16 Batta AK, Arora R, Salen G, Tint GS, Eskreis D, Katz S. Characterization of serum and urinary bile acids in patients with primary biliary cirrhosis by gas-liquid chromatography-mass spectrometry: effect of ursodeoxycholic acid treatment. J Lipid Res 1989; 30: 1953– 1962.MEDLINE 17 Crosignani A, Podda M, Battezzati PM, Bertolini E, Zuin M, Watson D, Setchell KD, et al. Changes in bile acid composition in patients with primary biliary cirrhosis induced by ursodeoxycholic acid administration. Hepatology 1991; 14: 1000– 1007.MEDLINE 18 Stiehl A, Rudolph G, Raedsch R, Moller B, Hopf U, Lotterer E, Bircher J, et al. Ursodeoxycholic acid-induced changes of plasma and urinary bile acids in patients with primary biliary cirrhosis. Hepatology 1990; 12: 492– 497.MEDLINE 19 Poupon RE, Chretien Y, Poupon R, Paumgartner G. Serum bile acids in primary biliary cirrhosis: effect of ursodeoxycholic acid therapy. Hepatology 1993; 17: 599– 604.MEDLINE 20 Javitt JB. Cholestasis in rats induced by taurolithocholate. Nature 1966; 210: 1262– 1263.MEDLINE 21 Kitani K, Ohta M, Kanai S. Tauroursodeoxycholate prevents biliary protein excretion induced by other bile salts in the rat. Am J Physiol 1985; 248: G407– 417.MEDLINE 22 Heuman DM, Mills AS, McCall J, Hylemon PB, Pandak WM, Vlahcevic ZR. Conjugates of ursodeoxycholate protect against cholestasis and hepatocellular necrosis caused by more hydrophobic bile salts. In vivo studies in the rat. Gastroenterology 1991; 100: 203– 211.MEDLINE 23 Van Nieuwkerk CM, Oude Elferink RP, Groen AK, Ottenhoff R, Tytgat GN, Dingemans KP, Van Den Bergh Weerman MA, et al. Effects of ursodeoxycholate and cholate feeding on liver disease in FVB mice with a disrupted mdr2 P-glycoprotein gene. Gastroenterology 1996; 111: 165– 171.MEDLINE 24 Holsti P. Cirrhosis of the liver induced in rabbits by gastric instillation of 3-monohydroxy-cholynic acid. Nature 1960; 186: 250. 25 Greim H, Trulzsch D, Roboz J, Dressler K, Czygan P, Hutterer F, Schaffner F, et al. Mechanisms of cholestasis. 5. Bile acids in normal rat livers and in those after bile duct ligation. Gastroenterology 1972; 63: 837– 845.MEDLINE 26 Greim H, Trulzsch D, Czygan P, Rudick J, Hutterer F, Schaffner F, Popper H. Mechanism of cholestasis. 6. Bile acids in human livers with or without biliary obstruction. Gastroenterology 1972; 63: 846– 850.MEDLINE 27 Schmucker DL, Ohta M, Kanai S, Sato Y, Kitani K. Hepatic injury induced by bile salts: correlation between biochemical and morphological events. Hepatology 1990; 12: 1216– 1221.MEDLINE 28 Attili AF, Angelico M, Cantafora A, Alvaro D, Capocaccia L. Bile acid-induced liver toxicity: relation to the hydrophobic-hydrophilic balance of bile acids. Med Hypotheses 1986; 19: 57– 69.MEDLINE 29 Hofmann AF. Bile acid hepatotoxicity and the rationale of UDCA therapy in chronic cholestatic liver disease: some hypotheses. In: G Paumgartner, A Stiehl, L Barbara, E Roda, eds. Strategies for the Treatment of Hepatobiliary Diseases. Lancaster: Kluwer. 1990; 13– 33. 30 Reichen J, Simon R. Cholestasis. In: IM Arias, JL Boyer, N Fausto, WB Jakoby, DA Schachter, DA Shafritz, eds. The Liver. Biology and Pathobiology. New York: Raven Press. 1994; 1291– 1326. 31 Patel T, Spivey J, Vadakekalam J, Gores GJ. Apoptosis—an alternative mechanism of bile salt hepatotoxicity. In: G Paumgartner, U Beuers, eds. Bile Acids in Liver Diseases. Lancaster: Kluwer. 1995; 88– 95. 32 Kitani K, Kanai S. Tauroursodeoxycholate prevents taurocholate-induced cholestasis. Life Sci 1982; 30: 515– 523.MEDLINE 33 Galle PR, Theilmann L, Raedsch R, Otto G, Stiehl A. Ursodeoxycholate reduces hepatotoxicity of bile salts in primary human hepatocytes. Hepatology 1990; 12: 486– 491.MEDLINE 34 Heuman DM, Pandak WM, Hylemon PB, Vlahcevic ZR. Conjugates of ursodeoxycholate protect against cytotoxicity of more hydrophobic bile salts: in vitro studies in rat hepatocytes and human erythrocytes. Hepatology 1991; 14: 920– 926.MEDLINE 35 Schölmerich J, Baumgartner U, Miyai K, Gerok W. Tauroursodeoxycholate prevents taurolithocholate-induced cholestasis and toxicity in rat liver. J Hepatol 1990; 10: 280– 283.MEDLINE 36 Baumgartner U, Schölmerich J, Sellinger M, Reinhardt M, Ruf G, Farthmann EH. Different protective effects of tauroursodeoxycholate, ursodeoxycholate, and 23-methyl-ursodeoxycholate against taurolithocholate-induced cholestasis. Dig Dis Sci 1996; 41: 250– 255.MEDLINE 37 Tsukahara K, Kanai S, Ohta M, Kitani K. Taurine conjugate of ursodeoxycholate plays a major role in the hepatoprotective effect against cholestasis induced by taurochenodeoxycholate in rats. Liver 1993; 13: 262– 269.MEDLINE 38 Smit JJ, Schinkel AH, Oude Elferink RP, Groen AK, Wagenaar E, van Deemter L, Mol CA, et al. Homozygous disruption of the murine mdr2 P-glycoprotein gene leads to a complete absence of phospholipid from bile and to liver disease. Cell 1993; 75: 451– 462.MEDLINE 39 Güldütuna S, Zimmer G, Imhof M, Bhatti S, You T, Leuschner U. Molecular aspects of membrane stabilization by ursodeoxycholate. Gastroenterology 1993; 104: 1736– 1744.MEDLINE 40 Heuman DM, Bajaj R. Ursodeoxycholate conjugates protect against disruption of cholesterol-rich membranes by bile salts. Gastroenterology 1994; 106: 1333– 1341.MEDLINE 41 Heuman DM. Disruptive and protective interactions of bile salts, cholesterol: lecithin vesicles, and canalicular membranes. In: AF Hofmann, G Paumgartner, A Stiehl, eds. Bile Acids in Gastroenterology. Lancaster: Kluwer. 1995; 283– 289. 42 Heuman DM, Bajaj RS, Lin Q. Adsorption of mixtures of bile salt taurine conjugates to lecithin-cholesterol membranes: implications for bile salt toxicity and cytoprotection. J Lipid Res 1996; 37: 562– 573.MEDLINE 43 Jazrawi RP, de Caestecker JS, Goggin PM, Britten AJ, Joseph AE, Maxwell JD, Northfield TC, et al. Kinetics of hepatic bile acid handling in cholestatic liver disease: effect of ursodeoxycholic acid. Gastroenterology 1994; 106: 134– 142.MEDLINE 44 Stiehl A, Rudolph G, Sauer P, Theilmann L. Biliary secretion of bile acids and lipids in primary sclerosing cholangitis. Influence of cholestasis and effect of ursodeoxycholic acid treatment. J Hepatol 1995; 23: 283– 289.MEDLINE 45 Ohiwa T, Katagiri K, Hoshino M, Hayakawa T, Nakai T. Tauroursodeoxycholate and tauro-beta-muricholate exert cytoprotection by reducing intrahepatocyte taurochenodeoxycholate content. Hepatology 1993; 17: 470– 476.MEDLINE 46 Poupon RE, Balkau B, Eschwege E, Poupon R. A multicenter, controlled trial of ursodiol for the treatment of primary biliary cirrhosis. UDCA-PBC Study Group. N Engl J Med 1991; 324: 1548– 1554.MEDLINE 47 Heathcote EJ, Cauch Dudek K, Walker V, Bailey RJ, Blendis LM, Ghent CN, Michieletti P, et al. The Canadian multicenter double-blind randomized controlled trial of ursodeoxycholic acid in primary biliary cirrhosis. Hepatology 1994; 19: 1149– 1156.MEDLINE 48 Lindor KD, Dickson ER, Baldus WP, Jorgensen RA, Ludwig J, Murtaugh PA, Harrison JM, et al. Ursodeoxycholic acid in the treatment of primary biliary cirrhosis. Gastroenterology 1994; 106: 1284– 1290.MEDLINE 49 Combes B, Carithers RL, Maddrey WC, Lin D, McDonald MF, Wheeler DE, Eigenbrodt EH, et al. A randomized, double-blind, placebo-controlled trial of ursodeoxycholic acid in primary biliary cirrhosis. Hepatology 1995; 22: 759– 766.MEDLINE 50 Beuers U, Spengler U, Kruis W, Aydemir Ü, Wiebecke B, Heldwein W, Weinzierl M, et al. Ursodeoxycholic acid for treatment of primary sclerosing cholangitis: A double-blind, placebo-controlled trial. Hepatology 1992; 16: 707– 714.MEDLINE 51 Lindor KD. Ursodiol for primary sclerosing cholangitis. N Engl J Med 1997; 336: 691– 695.MEDLINE 52 Colombo C, Castellani MR, Balistreri WF, Seregni E, Assaisso ML, Giunta A. Scintigraphic documentation of an improvement in hepatobiliary excretory function after treatment with ursodeoxycholic acid in patients with cystic fibrosis and associated liver disease. Hepatology 1992; 15: 677– 684.MEDLINE 53 Müller M, Jansen PL. The secretory function of the liver: new aspects of hepatobiliary transport. J Hepatol 1998; 28: 344– 354.MEDLINE 54 Benedetti A, Strazzabosco M, Ng OC, Boyer JL. Regulation of activity and apical targeting of the Cl−/HCO3− exchanger in rat hepatocytes. Proc Natl Acad Sci U S A 1994; 91: 792– 796.MEDLINE 55 Boyer JL, Soroka CJ. Vesicle targeting to the apical domain regulates bile excretory function in isolated rat hepatocyte couplets. Gastroenterology 1995; 109: 1600– 1611.MEDLINE 56 Crawford JM. Role of vesicle-mediated transport pathways in hepatocellular bile secretion. Semin Liver Dis 1996; 16: 169– 189.MEDLINE 57 Larkin JM, Palade GE. Transcytotic vesicular carriers for polymeric IgA receptors accumulate in rat hepatocytes after bile duct ligation. J Cell Sci 1991; 98: 205– 216.MEDLINE 58 Barr VA, Hubbard AL. Newly synthesized hepatocyte plasma membrane proteins are transported in transcytotic vesicles in the bile duct-ligated rat. Gastroenterology 1993; 105: 554– 571.MEDLINE 59 Beuers U, Nathanson MH, Isales CM, Boyer JL. Tauroursodeoxycholic acid stimulates hepatocellular exocytosis and mobilizes extracellular Ca++ mechanisms defective in cholestasis. J Clin Invest 1993; 92: 2984– 2993.MEDLINE 60 Häussinger D, Saha N, Hallbrucker C, Lang F, Gerok W. Involvement of microtubules in the swelling-induced stimulation of transcellular taurocholate transport in perfused rat liver. Biochem J 1993; 291: 355– 360.MEDLINE 61 Crawford JM, Strahs DC, Crawford AR, Barnes S. Role of bile salt hydrophobicity in hepatic microtubule-dependent bile salt secretion. J Lipid Res 1994; 35: 1738– 1748.MEDLINE 62 Beuers U, Throckmorton DC, Anderson MS, Isales CM, Thasler W, Kullak-Ublick GA, Sauter G, et al. Tauroursodeoxycholic acid activates protein kinase C in isolated rat hepatocytes. Gastroenterology 1996; 110: 1553– 1563.MEDLINE 63 Schliess F, Kurz AK, vom Dahl S, Häussinger D. Mitogen-activated protein kinases mediate the stimulation of bile acid secretion by tauroursodeoxycholate in rat liver. Gastroenterology 1997; 113: 1306– 1314.MEDLINE 64 Burgoyne RD, Morgan A. Regulated exocytosis. Biochem J 1993; 293: 305– 316.MEDLINE 65 Nathanson MH, Boyer JL. Mechanisms and regulation of bile secretion. Hepatology 1991; 14: 551– 566.MEDLINE 66 Beuers U, Nathanson MH, Boyer JL. Effects of tauroursodeoxycholic acid on cytosolic Ca++ signals in isolated rat hepatocytes. Gastroenterology 1993; 104: 604– 612.MEDLINE 67 Bouscarel B, Fromm H, Nussbaum R. Ursodeoxycholate mobilizes intracellular Ca++ and activates phosphorylase a in isolated hepatocytes. Am J Physiol 1993; 264: G243– G251.MEDLINE 68 Beuers U, Thiel M, Bardenheuer H, Paumgartner G. Tauroursodeoxycholic acid inhibits the cytosolic Ca++ increase in human neutrophils stimulated by formyl-methionyl-leucyl-phenylalanine. Biochem Biophys Res Commun 1990; 171: 1115– 1121.MEDLINE 69 Bouscarel B, Gettys TW, Fromm H, Dubner H. Ursodeoxycholic acid inhibits glucagon-induced cAMP formation in hamster hepatocytes: a role for PKC. Am J Physiol 1995; 268: G300– G310.MEDLINE 70 Stravitz RT, Rao YP, Vlahcevic ZR, Gurley EC, Jarvis WD, Hylemon PB. Hepatocellular protein kinase C activation by bile acids: implications for regulation of cholesterol 7α-hydroxylase. Am J Physiol 1996; 271: G293– G303.MEDLINE 71 Roman R, Schlenker T, Fitz JG. Ursodeoxycholic acid activates Ca2+-dependent Cl− currents in a human biliary cell line. In: G Paumgartner, A Stiehl, W Gerok, eds. Bile Acids in Hepatobiliary Diseases. Lancaster: Kluwer Academic Publishers. 1997; 219– 223. 72 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; 11: 12– 15.MEDLINE 73 Calmus Y, Arvieux C, Gane P, Boucher E, Nordlinger B, Rouger P, Poupon R, et al. Cholestasis induces major histocompatibility complex class I expression in hepatocytes. Gastroenterology 1992; 102: 1371– 1377.MEDLINE 74 Hillaire S, Boucher E, Calmus Y, Gane P, Ballet F, Franco D, Moukthar M, et al. Effects of bile acids and cholestasis on major histocompatibility complex class I in human and rat hepatocytes. Gastroenterology 1994; 107: 781– 788.MEDLINE 75 Dickson ER, Grambsch PM, Fleming TR, Fisher LD, Langworthy A. Prognosis in primary biliary cirrhosis: model for decision making. Hepatology 1989; 10: 1– 7.MEDLINE 76 Christensen E, Altman DG, Neuberger J, De Stavola BL, Tygstrup N, Williams R. Updating prognosis in primary biliary cirrhosis using a time-dependent Cox regression model. PBC1 and PBC2 trial groups. Gastroenterology 1993; 105: 1865– 1876.MEDLINE 77 Stiehl A, Walker S, Stiehl L, Rudolph G, Hofmann WJ, Theilmann L. Effect of ursodeoxycholic acid on liver and bile duct disease in primary sclerosing cholangitis. A 3-year pilot study with a placebo-controlled study period. J Hepatol 1994; 20: 57– 64.MEDLINE 78 Dickson ER, Murtaugh PA, Wiesner RH, Grambsch PM, Fleming TR, Ludwig J, LaRusso NF, et al. Primary sclerosing cholangitis: refinement and validation of survival models. Gastroenterology 1992; 103: 1893– 1901.MEDLINE 79 Broome U, Olsson R, Loof L, Bodemar G, Hultcrantz R, Danielsson A, Prytz H, et al. Natural history and prognostic factors in 305 Swedish patients with primary sclerosing cholangitis. Gut 1996; 38: 610– 615.MEDLINE 80 Stiehl A, Rudolph G, Sauer P, Benz C, Stremmel W, Walker S, Theilmann L, et al. Efficacy of ursodeoxycholic acid treatment and endoscopic dilation of major duct stenoses in primary sclerosing cholangitis. An 8-year prospective study. J Hepatol 1997; 26: 560– 566.MEDLINE 81 Palma J, Reyes H, Ribalta J, Hernandez I, Sandoval L, Almuna R, Liepins J, et al. Ursodeoxycholic acid in the treatment of cholestasis of pregnancy: a randomized, double-blind study controlled with placebo. J Hepatol 1997; 27: 1022– 1028.MEDLINE 82 Colombo C, Battezzati PM, Podda M, Bettinardi N, Giunta A. Ursodeoxycholic acid for liver disease associated with cystic fibrosis: a double-blind multicenter trial. The Italian Group for the Study of Ursodeoxycholic Acid in Cystic Fibrosis. Hepatology 1996; 23: 1484– 1490.MEDLINE 83 Lindblad A, Glaumann H, Strandvik B. A two-year prospective study of the effect of ursodeoxycholic acid on urinary bile acid excretion and liver morphology in cystic fibrosis–associated liver disease. Hepatology 1998; 27: 166– 174.MEDLINE 84 van de Meeberg PC, Houwen RH, Sinaasappel M, Heijerman HG, Bijleveld CM, van Berge Henegouwen GP. Low-dose versus high-dose ursodeoxycholic acid in cystic fibrosis-related cholestatic liver disease. Results of a randomized study with 1-year follow-up. Scand J Gastroenterol 1997; 32: 369– 373.MEDLINE 85 Jacquemin E, Hermans D, Myara A, Habes D, Debray D, Hadchouel M, Sokal EM, et al. Ursodeoxycholic acid therapy in pediatric patients with progressive familial intrahepatic cholestasis. Hepatology 1997; 25: 519– 523.MEDLINE 86 Balistreri WF, Setchell KD, Ryckman FC. Bile acid therapy in paediatric liver disease. In: G Paumgartner, A Stiehl, W Gerok, eds. Bile Acids and the Hepatobiliary System. UDCA Study Group. London: Kluwer Academic Publishers. 1993; 271– 282. 87 Nittono H, Tokita A, Hayashi M, Watanabe T, Obinata K, Nakatsu N, Miyano T, et al. Ursodeoxycholic acid therapy in the treatment of biliary atresia. Biomed Pharmacother 1989; 43: 37– 41.MEDLINE 88 Spagnuolo MI, Iorio R, Vegnente A, Guarino A. Ursodeoxycholic acid for treatment of cholestasis in children on long-term total parenteral nutrition: a pilot study. Gastroenterology 1996; 111: 716– 719.MEDLINE 89 Fried RH, Murakami CS, Fisher LD, Willson RA, Sullivan KM, McDonald GB. Ursodeoxycholic acid treatment of refractory chronic graft-versus-host disease of the liver. Ann Intern Med 1992; 116: 624– 629.MEDLINE 90 Pageaux GP, Blanc P, Perrigault PF, Navarro F, Fabre JM, Souche B, Domergue J, et al. Failure of ursodeoxycholic acid to prevent acute cellular rejection after liver transplantation. J Hepatol 1995; 23: 119– 122.MEDLINE 91 Keiding S, Hockerstedt K, Bjoro K, Bondesen S, Hjortrup A, Isoniemi H, Erichsen C, et al. The Nordic multicenter double-blind randomized controlled trial of prophylactic ursodeoxycholic acid in liver transplant patients. Transplantation 1997; 63: 1591– 1594.MEDLINE 92 Barnes D, Talenti D, Cammell G, Goormastic M, Farquhar L, Henderson M, Vogt D, et al. A randomized clinical trial of ursodeoxycholic acid as adjuvant treatment to prevent liver transplant rejection. Hepatology 1997; 26: 853– 857.MEDLINE 93 Boucher E, Jouanolle H, Andre P, Ruffault A, Guyader D, Moirand R, Turlin B, et al. Interferon and ursodeoxycholic acid combined therapy in the treatment of chronic viral C hepatitis: results from a controlled randomized trial in 80 patients. Hepatology 1995; 21: 322– 327.MEDLINE 94 Angelico M, Gandin C, Pescarmona E, Rapicetta M, Del Vecchio C, Bini A, Spada E, et al. Recombinant interferon-alpha and ursodeoxycholic acid versus interferon-alpha alone in the treatment of chronic hepatitis C: a randomized clinical trial with long-term follow-up. Am J Gastroenterol 1995; 90: 263– 269.MEDLINE 95 Bellentani S, Podda M, Tiribelli C, Callea F, Marazzi M, Sodde M, Merlini R, et al. Ursodiol in the long-term treatment of chronic hepatitis: a double-blind multicenter clinical trial. J Hepatol 1993; 19: 459– 464.MEDLINE Citing Literature Volume28, Issue6December 1998Pages 1449-1453 ReferencesRelatedInformation
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