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Meta-Analysis
. 2011 Jan 19;2011(1):CD003626.
doi: 10.1002/14651858.CD003626.pub2.

Bile acids for primary sclerosing cholangitis

Goran Poropat  1 , Vanja Giljaca, Davor Stimac, Christian Gluud
Affiliations
Meta-Analysis

Bile acids for primary sclerosing cholangitis

Goran Poropat et al. Cochrane Database Syst Rev. .

Abstract

Background: Primary sclerosing cholangitis is a progressive chronic cholestatic liver disease that usually leads to the development of cirrhosis. Studies evaluating bile acids in the treatment of primary sclerosing cholangitis have shown a potential benefit of their use. However, no influence on patients survival and disease outcome has yet been proven.

Objectives: To assess the beneficial and harmful effects of bile acids for patients with primary sclerosing cholangitis.

Search strategy: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Library, MEDLINE, EMBASE and Science Citation Index Expanded generally from inception through to October 2010.

Selection criteria: Randomised clinical trials comparing any dose of bile acids or duration of treatment versus placebo, no intervention, or another intervention were included irrespective of blinding, language, or publication status.

Data collection and analysis: Two authors extracted data independently. We evaluated the risk of bias of the trials using prespecified domains. We performed the meta-analysis according to the intention-to-treat principle. We presented outcomes as relative risks (RR) or mean differences (MD), both with 95% confidence intervals (CI).

Main results: Eight trials evaluated ursodeoxycholic acid versus placebo or no intervention (592 patients). The eight randomised clinical trials have a high risk of bias. Patients were treated for three months to six years (median three years). The dosage of ursodeoxycholic acid used in the trials ranged from low (10 mg/kg body weight/day) to high (28 to 30 mg/kg body weight/day). Ursodeoxycholic acid did not significantly reduce the risk of death (RR 1.00; 95% CI 0.46 to 2.20); treatment failure including liver transplantation, varices, ascites, and encephalopathy (RR 1.22; 95% CI 0.91 to 1.64); liver histological deterioration (RR 0.89; 95% CI 0.45 to 1.74); or liver cholangiographic deterioration (RR 0.60; 95% CI 0.23 to 1.57). Ursodeoxycholic acid significantly improved serum bilirubin (MD -14.6 µmol/litre; 95% CI -18.7 to -10.6), alkaline phosphatases (MD -506 IU/litre; 95% CI -583 to -430), aspartate aminotransferase (MD -46 IU/litre; 95% CI -77 to -16), and gamma-glutamyltranspeptidase (MD -260 IU/litre; 95% CI -315 to -205), but not albumin (MD -0.20 g/litre; 95% CI -1.91 to 1.50). Ursodeoxycholic acid was safe and well tolerated by patients with primary sclerosing cholangitis.

Authors' conclusions: We did not find enough evidence to support or refute the use of bile acids in the treatment of primary sclerosing cholangitis. However, bile acids seem to lead to a significant improvement in liver biochemistry. Therefore, more randomised trials are needed before any of the bile acids can be recommended for this indication.

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Conflict of interest statement

None known.

Figures

1
1
Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
2
2
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
1.1
1.1. Analysis
Comparison 1 UDCA versus control (placebo or no treatment), Outcome 1 Mortality at the end of treatment.
1.2
1.2. Analysis
Comparison 1 UDCA versus control (placebo or no treatment), Outcome 2 Number of treatment failures at the end of treatment.
1.3
1.3. Analysis
Comparison 1 UDCA versus control (placebo or no treatment), Outcome 3 Adverse events.
1.4
1.4. Analysis
Comparison 1 UDCA versus control (placebo or no treatment), Outcome 4 Quality of life ‐ physical component.
1.5
1.5. Analysis
Comparison 1 UDCA versus control (placebo or no treatment), Outcome 5 Quality of life ‐ mental component.
1.6
1.6. Analysis
Comparison 1 UDCA versus control (placebo or no treatment), Outcome 6 Number of patients with liver histological deterioration at the end of treatment.
1.7
1.7. Analysis
Comparison 1 UDCA versus control (placebo or no treatment), Outcome 7 Histological inflammatory score at the end of treatment.
1.8
1.8. Analysis
Comparison 1 UDCA versus control (placebo or no treatment), Outcome 8 Number of patients with cholangiographic deterioration at the end of treatment.
1.9
1.9. Analysis
Comparison 1 UDCA versus control (placebo or no treatment), Outcome 9 Number of patients with worsening clinical symptoms (fatigue and/or pruritus) at the end of treatment.
1.10
1.10. Analysis
Comparison 1 UDCA versus control (placebo or no treatment), Outcome 10 Serum bilirubin level (µmol/l) at the end of treatment.
1.11
1.11. Analysis
Comparison 1 UDCA versus control (placebo or no treatment), Outcome 11 Serum alkaline phosphatases activity (IU/L) at the end of treatment.
1.12
1.12. Analysis
Comparison 1 UDCA versus control (placebo or no treatment), Outcome 12 Serum aspartate aminotransferase activity (IU/L) at the end of treatment.
1.13
1.13. Analysis
Comparison 1 UDCA versus control (placebo or no treatment), Outcome 13 Serum gamma‐glutamyltranspeptidase activity (IU/L) at the end of treatment.
1.14
1.14. Analysis
Comparison 1 UDCA versus control (placebo or no treatment), Outcome 14 Serum albumin concentration (g/l) at the end of treatment.
2.1
2.1. Analysis
Comparison 2 Sensitivity analyses, Outcome 1 Mortality ‐ Duration of the treatment with UDCA.
2.2
2.2. Analysis
Comparison 2 Sensitivity analyses, Outcome 2 Mortality ‐ Dose of UDCA in the treatment.
2.3
2.3. Analysis
Comparison 2 Sensitivity analyses, Outcome 3 Mortality ‐ Different duration of the treatment with different dose of UDCA.
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Update of

References

References to studies included in this review

Beuers 1992 {published data only}
    1. Beuers U, Spengler U, Kruis W, Aydemir U, Heldwein W, Weinzierl M, et al. Effect of ursodeoxycholic acid in primary sclerosing cholangitis: a controlled trial. Hepatology 1991;14(4 pt 2):64A. - PubMed
    1. Beuers U, Spengler U, Kruis W, Aydemir U, Wiebecke B, Heldwein W, et al. Ursodeoxycholic acid for treatment of primary sclerosing cholangitis: a placebo‐controlled trial. Hepatology 1992;16(3):707‐14. [MEDLINE: ] - PubMed
de Maria 1996 {published data only}
    1. Maria N, Colantoni A, Rosenbloom E, Thiel DH. Ursodeoxycholic acid does not improve the clinical course of primary sclerosing cholangitis over a 2‐year period. Hepato‐Gastroenterology 1996;43(12):1472‐9. [MEDLINE: ] - PubMed
Lindor 1997 {published data only}
    1. Lindor KD, for the Mayo Primary Sclerosing Cholangitis‐Ursodeoxycholic Acid Study Group. Ursodiol for primary sclerosing cholangitis. The New England Journal of Medicine 1997;336(10):691‐5. [MEDLINE: ] - PubMed
Lindor 2009 {published data only}
    1. Lindor KD, Enders FB, Schmoll JA, Hoskin TL, Jorgensen RA, Petz JL, et al. Randomized, double‐blind controlled trial of high‐dose ursodeoxycholic acid (UDCA) for primary sclerosing cholangitis (PSC). Hepatology 2008;48(4 (Suppl)):378A.
    1. Lindor KD, Kowdley KV, Luketic VAC, Harrison ME, McCashland T, Befeler AS, et al. High‐dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis. Hepatology 2009;50(3):808‐14. [MEDLINE: ] - PMC - PubMed
Lo 1992 {published data only}
    1. Lo SK, Herrmann R, Chapman RW, Fleming KA, Shearman J, Cusick P, et al. Ursodeoxycholic acid in primary sclerosing cholangitis: a double‐blind placebo controlled trial [AASLD abstract]. Hepatology 1992;16(2 Pt 2):92A.
Mitchell 2001 {published data only}
    1. Bansi D, Christie J, Fleming K, Chapman R. High‐dose ursodeoxycholic acid in primary sclerosing cholangitis: a randomized double‐blind, placebo‐controlled trial. Gastroenterology 1996;110:1146A. - PubMed
    1. Mitchell SA, Bansi D, Hunt N, Christie J, Fleming K, Chapman R. High‐dose ursodeoxycholic acid (UDCA) in primary sclerosing cholangitis (PSC): results after two years of a randomised double‐blind, placebo‐controlled trial. Gut 1997;40(Suppl 1):A29.
    1. Mitchell SA, Bansi DS, Hunt N, Bergmann KV, Fleming KA, Chapman RW. A preliminary trial of high‐dose ursodeoxycholic acid in primary sclerosing cholangitis. Gastroenterology 2001;121(4):900‐7. [MEDLINE: ] - PubMed
Olsson 2005 {published data only}
    1. Olsson R, Boberg KM, Muckadell OS, Lindgren S, Hultcrantz R, Folvik G, et al. High‐dose ursodeoxycholic acid in primary sclerosing cholangitis: A 5‐year multicenter, randomized, controlled study. Gastroenterology 2005;129(5):1464‐72. [MEDLINE: ] - PubMed
Stiehl 1994 {published data only}
    1. Stiehl A, Raedsch R, Rudolph G, Theilmann L. Treatment of primary sclerosing cholangitis with ursodeoxycholic acid: first results of a controlled study. Hepatology 1989;10(4):602.
    1. 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. Journal of Hepatology 1994;20(1):57‐64. [MEDLINE: ] - PubMed

References to studies excluded from this review

Charatcharoenwitthaya '08 {published data only}
    1. Charatcharoenwitthaya P, Angulo P, Enders FB, Lindor KD. Impact of inflammatory bowel disease and ursodeoxycholic acid therapy on small‐duct primary sclerosing cholangitis. Hepatology 2008;47(1):133‐42. [MEDLINE: ] - PubMed
Chazouilleres 1990 {published data only}
    1. Chazouilleres O, Poupon R, Capron JP, Metman EH, Dhumeaux D, Amouretti M, et al. Ursodeoxycholic acid for primary sclerosing cholangitis. Journal of Hepatology 1990;11(1):120‐3. [MEDLINE: ] - PubMed
Garioud 2006 {published data only}
    1. Garioud A, Seksik P, Chretien Y, Corpechot C, Poupon R, Poupon RE, et al. Four‐year outcome of primary sclerosing cholangitis (PSC) under low‐dose ursodeoxycholic acid (UDCA): a French prospective study. Journal of Hepatology 2006;44(Suppl 2):S234‐S235. [DOI: 10.1016/S0168-8278(06)80632-X] - DOI
Gilger 2000 {published data only}
    1. Gilger MA, Gann ME, Opekun AR, Gleason WA Jr. Efficacy of ursodeoxycholic acid in the treatment of primary sclerosing cholangitis in children. Journal of Pediatric Gastroenterology and Nutrition 2000;31(2):136‐41. [MEDLINE: ] - PubMed
Harnois 2001 {published data only}
    1. Harnois DM, Angulo P, Jorgensen RA, Larusso NF, Lindor KD. High‐dose ursodeoxycholic acid as a therapy for patients with primary sclerosing cholangitis. American Journal of Gastroenterology 2001;96(5):1558‐62. [MEDLINE: ] - PubMed
O'Brien 1991 {published data only}
    1. O'Brien CB, Senior JR, Arora‐Mirchandani R, Batta AK, Salen G. Ursodeoxycholic acid for the treatment of primary sclerosing cholangitis: a 30‐month pilot study. Hepatology 1991;14(5):838‐47. [MEDLINE: ] - PubMed
Okolicsanyi 2003 {published data only}
    1. Okolicsanyi L, Groppo M, Floreani A, Morselli‐Labate AM, Rusticali AG, Battocchia A, et al. Treatment of primary sclerosing cholangitis with low‐dose ursodeoxycholic acid: results of a retrospective Italian multicentre survey. Digestive and Liver Disease 2003;35(5):325‐31. [MEDLINE: ] - PubMed
Rudolph 1991 {published data only}
    1. Rudolph G, Walker S, Theilmann L, Folsch U, Bircher J, Stiehl A. The effect of ursodeoxycholic acid on survival in patients with primary sclerosing cholangitis [EASL abstract]. Journal of Hepatology 1991;13(Suppl 2):S165.
Schonfeld 1996 {published data only}
    1. Schonfeld J, Zotz R, Mahl M, Beste M, Breuer N, Goebell H. Primary sclerosing cholangitis: conventional and quantitative liver function tests during long‐term therapy with ursodeoxycholic acid [Primar sklerosierende cholangitis: konventionelle und quantitative leberfunktionstests unter einer mehrjahrigen therapie mit ursodesoxycholsaure]. Zeitschrift fur Gastroenterologie 1996;34(2):123‐7. [MEDLINE: ] - PubMed
van de Meeberg 1996 {published data only}
    1. Meeberg PC, Wolfhagen FH, Berge‐Henegouwen GP, Salemans JM, Tangerman A, Buuren HR, et al. Single or multiple dose ursodeoxycholic acid for cholestatic liver disease: biliary enrichment and biochemical response. Journal of Hepatology 1996;25(6):887‐94. [MEDLINE: ] - PubMed
van Hoogstraten 1998 {published data only}
    1. Hoogstraten HJ, Wolfhagen FH, Meeberg PC, Kuiper H, Nix GA, Becx MC, et al. Ursodeoxycholic acid therapy for primary sclerosing cholangitis: results of a 2‐year randomized controlled trial to evaluate single versus multiple daily doses. Journal of Hepatology 1998;29(3):417‐23. [MEDLINE: ] - PubMed
van Hoogstraten 2000 {published data only}
    1. Hoogstraten HJ, Vleggaar FP, Boland GJ, Steenbergen W, Griffioen P, Hop WC, et al. Budesonide or prednisone in combination with ursodeoxycholic acid in primary sclerosing cholangitis: a randomized double‐blind pilot study. Belgian‐Dutch PSC Study Group. American Journal of Gastroenterology 2000;95(8):2015‐22. [MEDLINE: ] - PubMed
van Milligen 1999 {published data only}
    1. Milligen de Wit AW, Kuiper H, Camoglio L, Bracht J, Jones EA, Tytgat GN, et al. Does ursodeoxycholic acid mediate immunomodulatory and anti‐inflammatory effects in patients with primary sclerosing cholangitis?. European Journal of Gastroenterology and Hepatology 1999;11(2):129‐36. [MEDLINE: ] - PubMed
van Thiel 1992 {published data only}
    1. Thiel DH, Wright HI, Gavaler JS. Ursodeoxycholic acid (UDCA) therapy for primary sclerosing cholangitis (PSC): preliminary report of a randomised controlled trial [AASLD abstract]. Hepatology 1992;16(2 Pt 2):62A.

Additional references

Angulo 1999
    1. Angulo P, Lindor KD. Primary sclerosing cholangitis. Hepatology 1999;30(1):325‐32. [MEDLINE: ] - PubMed
Beuers 1993
    1. Beuers U, Nathanson MH, Isales CM, Boyer JL. Tauroursodeoxycholic acid stimulates hepatocellular exocytosis and mobilizes extracellular Ca++ mechanisms defective in cholestasis. Journal of Clinical Investigation 1993;92(6):2984‐93. [MEDLINE: ] - PMC - PubMed
Beuers 1996
    1. Beuers U, Throckmorton DC, Anderson MS, Isales CM, Thasler W, Kullak‐Ublick GA. Tauroursodeoxycholic acid activates protein kinase C in isolated rat hepatocytes. Gastroenterology 1996;110(5):1553‐63. [MEDLINE: ] - PubMed
Beuers 2001
    1. Beuers U, Bilzer M, Chittattu A, Kullak‐Ublick GA, Keppler D, Paumgartner G, et al. Tauroursodeoxycholic acid inserts the apical conjugate export pump, Mrp2, into canalicular membranes and stimulates organic anion secretion by protein kinase C‐dependent mechanisms in cholestatic rat liver. Hepatology 2001;33(5):1206‐16. [MEDLINE: ] - PubMed
Beuers 2009
    1. Beuers U, Kullak‐Ublick GA, Pusl T, Rauws ER, Rust C. Medical treatment of primary sclerosing cholangitis: a role for novel bile acids and other (post‐) transcriptional modulators?. Clinical Reviews in Allergy and Immunology 2009;36(1):52‐61. [MEDLINE: ] - PubMed
Brok 2009
    1. Brok J, Thorlund K, Wetterslev J, Gluud C. Apparently conclusive meta‐analysis may be inconclusive ‐ Trial sequential analysis adjustment of random error risk due to repetitive testing of accumulating data in apparently conclusive neonatal meta‐analysis. International Journal of Epidemiology 2009;38(1):298‐303. [MEDLINE: ] - PubMed
Burak 2003
    1. Burak KW, Angulo P, Lindor KD. Is there a role for liver biopsy in primary sclerosing cholangitis?. American Journal of Gastroenterology 2003;98(5):1155‐8. [MEDLINE: ] - PubMed
Calmus 1990
    1. 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(1):12‐5. [MEDLINE: ] - PubMed
Card 2008
    1. Card TR, Solaymani‐Dodaran M, West J. Incidence and mortality of primary sclerosing cholangitis in the UK: a population‐based cohort study. Journal of Hepatology 2008;48(6):939‐44. [MEDLINE: ] - PubMed
Chen 1984
    1. Chen LY, Goldberg HI. Sclerosing cholangitis: broad spectrum of radiographic features. Gastrointestinal Radiolology 1984;9(1):39‐47. [MEDLINE: ] - PubMed
Chen 2007
    1. Chen W, Liu J, Gluud C. Bile acids for viral hepatitis. Cochrane Database of Systematic Reviews 2007, Issue 4. [DOI: 10.1002/14651858.CD003181.pub2] - DOI - PMC - PubMed
Crosignani 1996
    1. Crosignani A, Battezzati PM, Setchell KDR, Invernizzi P, Covini G, Zuin M, et al. Tauroursodeoxycholic acid for treatment of primary biliary cirrhosis. A dose‐response study. Digestive Diseases and Sciences 1996;41(4):809‐15. [MEDLINE: ] - PubMed
Cullen 2005
    1. Cullen SN, Chapman RW. Review article: current management of primary sclerosing cholangitis. Alimentary Pharmacology and Therapeutics 2005;21(8):933‐48. [MEDLINE: ] - PubMed
Demets 1987
    1. Demets DL. Methods for combining randomized clinical trials: strengths and limitations. Statistics in Medicine 1987;6(3):341‐50. [MEDLINE: ] - PubMed
DerSimonian 1986
    1. DerSimonian R, Laird N. Meta‐analysis in clinical trials. Controlled Clinical Trials 1986;7(3):177‐88. [MEDLINE: ] - PubMed
Donaldson 1991
    1. Donaldson PT, Farrant JM, Wilkinson ML, Hayllar K, Portmann BC, Williams R. Dual association of HLA DR2 and DR3 with primary sclerosing cholangitis. Hepatology 1991;13(1):129‐33. [MEDLINE: ] - PubMed
Egger 1997
    1. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta‐analysis detected by a simple graphical test. BMJ (Clinical Research Ed.) 1997;315(7109):629‐34. [MEDLINE: ] - PMC - PubMed
Gluud 2001
    1. Gluud C. Alcoholic hepatitis: no glucocorticosteroids?. In: Leuschner U, James OFW, Dancygier H editor(s). Steatohepatitis (NASH and ASH). Falk Symposium 121. Lancaster: Kluwer Academic Publisher, 2001:322‐42.
Gluud 2007
    1. Gluud C, Brok J, Gong Y, Koretz RL. Hepatology may have problems with putative surrogate outcome measures. Journal of Hepatology 2007;46(4):734‐42. - PubMed
Gluud 2010
    1. Gluud C, Nikolova D, Klingenberg SL, Alexakis N, Als‐Nielsen B, Colli A, et al. Cochrane Hepato‐Biliary Group. About The Cochrane Collaboration (Cochrane Review Groups (CRGs)). 2010, Issue 9. Art. No.: LIVER.
Gong 2008
    1. Gong Y, Huang ZB, Christensen E, Gluud C. Ursodeoxycholic acid for primary biliary cirrhosis. Cochrane Database of Systematic Reviews 2008, Issue 3. [DOI: 10.1002/14651858.CD000551.pub2] - DOI - PubMed
Gordon 2008
    1. Gordon FD. Primary sclerosing cholangitis. Surgical Clinics of North America 2008;88(6):1385‐407. [MEDLINE: ] - PubMed
Guicciardi 2002
    1. Guicciardi M, Gores GJ. Ursodeoxycholic acid cytoprotection: dancing with death receptors and survival pathways. Hepatology 2002;35(4):971‐3. [MEDLINE: ] - PubMed
Higgins 2002
    1. Higgins JPT, Thompson SG. Quantifying heterogeneity in a meta‐analysis. Statistics in Medicine 2002;21(11):1539‐58. [MEDLINE: ] - PubMed
Higgins 2009
    1. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.2 [updated September 2009]. The Cochrane Colloboration, 2009. Available from www.cochrane‐handbook.org.
ICH‐GCP 1997
    1. International Conference on Harmonisation Expert Working Group. International conference on harmonisation of technical requirements for registration of pharmaceuticals for human use. ICH harmonised tripartite guideline. Guideline for good clinical practice1997 CFR & ICH Guidelines. Vol. 1, PA 19063‐2043, USA: Barnett International/PAREXEL, 1997.
Jaeschke 2002
    1. Jaeschke H, Gores GJ, Cederbaum AI, Hinson JA, Pessayre D, Lemasters JJ. Mechanisms of hepatotoxicity. Toxicological Sciences 2002;65(2):166‐76. [MEDLINE: ] - PubMed
Kaplan 2007
    1. Kaplan GG, Laupland KB, Butzner D, Urbanski SJ, Lee SS. The burden of large and small duct primary sclerosing cholangitis in adults and children: a population‐based analysis. American Journal of Gastroenterology 2007;102(5):1042‐9. [MEDLINE: ] - PubMed
Kim 2000
    1. Kim WR, Therneau TM, Wiesner RH, Poterucha JJ, Benson JT, Malinchoc M, et al. A revised natural history model for primary sclerosing cholangitis. Mayo Clinic Proceedings 2000;75(7):688‐94. [MEDLINE: ] - PubMed
Kjaergard 2001
    1. Kjaergard LL, Villumsen J, Gluud C. Reported methodological quality and discrepancies between large and small randomized trials in meta‐analyses. Annals of Internal Medicine 2001;135(11):982‐9. [MEDLINE: ] - PubMed
LaRusso 1999
    1. LaRusso NF, Wiesner RH, Ludwig J. Sclerosing cholangitis. In: Bircher J, Benhamou JP, McIntyre N, Rizzetto M, Rodes J editor(s). Oxford Textbook of Clinical Hepatology. 2. Vol. II, Oxford: Oxford University Press, 1999:1121‐30.
Lee 1995
    1. Lee YM, Kaplan MM. Primary sclerosing cholangitis. New England Journal of Medicine 1995;332(14):924‐33. [MEDLINE: ] - PubMed
Linder 2001
    1. Linder S, Soderlund C. Endoscopic therapy in primary sclerosing cholangitis: outcome of treatment and risk of cancer. Hepatogastroenterology 2001;48(38):387‐92. [MEDLINE: ] - PubMed
Lindor 1987
    1. Lindor KD, Wiesner RH, LaRusso NF. Recent advances in the management of primary sclerosing cholangitis. Seminars in Liver Disease 1987;7(4):322‐7. [MEDLINE: ] - PubMed
Ludwig 1981
    1. Ludwig J, Barham SS, LaRusso NF, Elveback LR, Wiesner RH, McCall JT. Morphologic features of chronic hepatitis associated with primary sclerosing cholangitis and chronic ulcerative colitis. Hepatology 1981;1(6):632‐40. [MEDLINE: ] - PubMed
Ludwig 1986
    1. Ludwig J, LaRusso NF, Wiesner RH. Primary sclerosing cholangitis. In: Peters RL, Craig JR editor(s). Liver Pathology‐Contemporary Issues in Surgical Pathology. New York: Churchill Livingstone, 1986:193‐213.
Ludwig 1991
    1. Ludwig J. Small‐duct primary sclerosing cholangitis. Seminars in Liver Disease 1991;11(1):11‐7. [MEDLINE: ] - PubMed
Meagher 2007
    1. Meagher S, Yusoff I, Kennedy W, Martel M, Adam V, Barkun A. The roles of magnetic resonance and endoscopic retrograde cholangiopancreatography (MRCP and ERCP) in the diagnosis of patients with suspected sclerosing cholangitis: a cost‐effectiveness analysis. Endoscopy 2007;39(3):222‐8. [MEDLINE: ] - PubMed
Michaels 2008
    1. Michaels A, Levy C. Endoscopic and surgical management of primary sclerosing cholangitis. Medscape Journal of Medicine 2008;10(10):242. [MEDLINE: ] - PMC - PubMed
Moher 1998
    1. Moher D, Pham B, Jones A, Cook DJ, Jadad AR, Moher M, et al. Does quality of reports of randomised trials affect estimates of intervention efficacy reported in meta‐analyses. Lancet 1998;352(9128):609‐13. [MEDLINE: ] - PubMed
Olerup 1995
    1. Olerup O, Olsson R, Hultcrantz R, Broome U. HLA‐DR and HLA‐DQ are not markers for rapid disease progression in primary sclerosing cholangitis. Gastroenterology 1995;108(3):937‐40. [MEDLINE: ] - PubMed
Palmer 1972
    1. Palmer RH. Bile acids, liver injury and liver disease. Archives of Internal Medicine 1972;130(4):606‐17. [MEDLINE: ] - PubMed
Paumgartner 2002
    1. Paumgartner G, Beuers U. Ursodeoxycholiic acid in cholestatic liver disease: mechanisms of action and therapeutic use revisited. Hepatology 2002;36(3):525‐31. [MEDLINE: ] - PubMed
Paumgartner 2004
    1. Paumgartner G, Beuers U. Mechanisms of action and therapeutic efficacy of ursodeoxycholic acid in cholestatic liver disease. Clinics in Liver Disease 2004;8(1):67‐81. [MEDLINE: ] - PubMed
Perez 2009
    1. Perez MJ, Briz O. Bile‐acid‐induced cell injury and protection. World Journal of Gastroenterology 2009;15(14):1677‐89. [MEDLINE: ] - PMC - PubMed
Podda 1996
    1. Podda M, Crosignani A, Battezzati PM, Quagliuolo M, Valsania C, Invernizzi P, et al. Tauroursodeoxycholic acid for the treatment of chronic hepatitis: a dose‐response study (IASL Abstract). Hepatology 1996;23(1):I‐70. [MEDLINE: ]
Qiao 2002
    1. Qiao L, Yacoub A, Studer E, Gupta S, Pei XY, Grant S, et al. Inhibition of the MAPK and PI3K pathways enhances UDCA‐induced apoptosis in primary rodent hepatocytes. Hepatology 2002;35(4):779‐89. [MEDLINE: ] - PubMed
RevMan 2008 [Computer program]
    1. The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version Version 5.0. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2008.
Royle 2003
    1. Royle P, Milne R. Literature searching for randomized controlled trials used in Cochrane reviews: rapid versus exhaustive searches. International Journal of Technology Assessment in Health Care 2003;19(4):591‐603. [MEDLINE: ] - PubMed
Schulz 1995
    1. Schulz KF, Chalmers I, Hayes R, Altman D. Empirical evidence of bias. JAMA 1995;273(5):408‐12. [MEDLINE: ] - PubMed
Shi 2009
    1. Shi J, Li Z, Zeng X, Lin Y, Xie WF. Ursodeoxycholic acid in primary sclerosing cholangitis: meta‐analysis of randomized controlled trials. Hepatology Research 2009;39(9):865‐73. [MEDLINE: ] - PubMed
Sholmerich 1984
    1. Sholmerich J, Becher MS, Schmidt KH, Schubert R, Kremer B, Felhaus S, et al. Influence of hydroxylation and conjugation of bile salts on their membrane damaging properties. Hepatology 1984;4(4):661‐7. [MEDLINE: ] - PubMed
Silveira 2008
    1. Silveira MG, Lindor KD. Primary sclerosing cholangitis. Canadian Journal of Gastroenterology 2008;22(8):689‐98. [MEDLINE: ] - PMC - PubMed
Stiehl 1996
    1. Stiehl A. Ursodeoxycholic acid in the treatment of primary sclerosing cholangitis. The Italian Journal of Gastroenterology 1996;28(3):178‐80. [MEDLINE: ] - PubMed
Stiehl 1997
    1. Stiehl A, Rudolph G, Sauer P, Benz C, Stremmel W, Walker S, et al. Efficacy of ursodeoxycholic acid treatment and endoscopic dilation of major duct stenoses in primary sclerosing cholangitis. An 8‐year prospective study. Journal of Hepatology 1997;26(3):560‐6. [MEDLINE: ] - PubMed
Talwalkar 2004
    1. Talwalkar JA, Angulo P, Johnson CD, Petersen BT, Lindor KD. Cost‐minimization analysis of MRC versus ERCP for the diagnosis of primary sclerosing cholangitis. Hepatology 2004;40(1):39‐45. [MEDLINE: ] - PubMed
Talwalkar 2005
    1. Talwalkar JA, Lindor KD. Primary sclerosing cholangitis. Inflammatory Bowel Diseases 2005;11(1):62‐72. [MEDLINE: ] - PubMed
Thorlund 2009
    1. Thorlund K, Devereaux PJ, Wetterslev J, Guyatt G, Ioannidis JP, Thabane L, et al. Can trial sequential monitoring boundaries reduce spurious inferences from meta‐analysis?. International Journal of Epidemiology 2009;38(1):276‐86. [MEDLINE: ] - PubMed
Tischendorf 2008
    1. Tischendorf JJ, Geier A, Trautwein C. Current diagnosis and management of primary sclerosing cholangitis. Liver Transplantation 2008;14(6):735‐46. [MEDLINE: ] - PubMed
Van Nieuwkerk 1996
    1. Nieuwkerk CM, Elferink RP, Groen AK, Ottenhoff R, Tytgat GN, Dingemans KP, et al. Effects of Ursodeoxycholate and cholate feeding on liver disease in FVB mice with a disrupted mdr2 P‐glycoprotein gene. Gastroenterology 1996;111(1):165‐71. [MEDLINE: ] - PubMed
Wee 1985a
    1. Wee A, Ludwig J. Pericholangitis in chronic ulcerative colitis: primary sclerosing cholangitis of the small bile ducts?. Annals of Internal Medicine 1985;102(5):581‐7. [MEDLINE: ] - PubMed
Wee 1985b
    1. Wee A, Ludwig J, Coffey RJ Jr, LaRusso NF, Wiesner RH. Hepatobiliary carcinoma associated with primary sclerosing cholangitis and chronic ulcerative colitis. Human Pathology 1985;16(7):719‐26. [MEDLINE: ] - PubMed
Wetterslev 2008
    1. Wetterslev J, Thorlund K, Brok J, Gluud C. Trial sequential analysis may establish when firm evidence is reached in cumulative meta‐analysis. Journal of Clinical Epidemiology 2008;61(1):64‐75. [MEDLINE: ] - PubMed
Wood 2008
    1. Wood L, Egger M, Gluud LL, Schulz KF, Juni P, Altman DG, et al. Empirical evidence of bias in treatment effect estimates in controlled trials with different interventions and outcomes: meta‐epidemiological study. BMJ (Clinical Research Ed.) 2008;336(7644):601‐5. [MEDLINE: ] - PMC - PubMed
Yoshikawa 1998
    1. Yoshikawa M, Matsui Y, Kawamoto H, Toyohara M, Matsumura K, Yamao J, et al. Intragastric administration of ursodeoxycholic acid suppresses immunoglobulin secretion by lymphocytes from liver, but not from peripheral blood, spleen and Peyer's patches in mice. International Journal of Immunopharmacology 1998;20(1‐3):29‐38. [MEDLINE: ] - PubMed

References to other published versions of this review

Chen 2003
    1. Chen W, Gluud C. Bile acids for primary sclerosing cholangitis. Cochrane Database of Systematic Reviews 2003, Issue 2. [DOI: 10.1002/14651858.CD003626] - DOI - PubMed

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