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Meta-Analysis
. 2005 Apr 18;2005(2):CD003778.
doi: 10.1002/14651858.CD003778.pub2.

Glucocorticosteroids for primary biliary cirrhosis

M Prince  1 , E Christensen, C Gluud
Affiliations
Meta-Analysis

Glucocorticosteroids for primary biliary cirrhosis

M Prince et al. Cochrane Database Syst Rev. .

Abstract

Background: Primary biliary cirrhosis is a chronic progressive cholestatic liver disease of presumed autoimmune etiology, characterised by the destruction of small intrahepatic bile ducts and the eventual development of cirrhosis and liver failure. Its progression may be influenced by immunosuppression. Glucocorticosteroids are potent immunosuppressive agents, but they are associated with significant adverse effects, including osteoporosis.

Objectives: To systematically evaluate the beneficial and harmful effects of glucocorticosteroids versus placebo or no intervention for patients with primary biliary cirrhosis.

Search strategy: The Cochrane Hepato-Biliary Controlled Trials Register,The Cochrane Library, MEDLINE, EMBASE, and the full text of the identified studies were searched until June 2004. The search strategy included terms for primary biliary cirrhosis and glucocorticosteroids (including the names of frequently used preparations). Previous research groups and manufacturers were contacted for additional references. No language restrictions were applied.

Selection criteria: Double-blind, single-blind, or unblinded randomised clinical trials evaluating any preparation of glucocorticosteroids versus placebo or no intervention in patients with primary biliary cirrhosis diagnosed by abnormal liver function tests and either anti-mitochondrial antibodies or histology were included. Additional agents were allowed if they were administered to both groups equally.

Data collection and analysis: The quality of the randomised clinical trials was evaluated by methodology components (generation of allocation sequence; allocation concealment; blinding; follow up). Analyses were performed according to the intention-to-treat method with missing data being accounted for by imputation.

Main results: Only two underpowered trials (reporting 36 and 40 patients) were identified. These differed markedly in their inclusion criteria and treatment protocols. Both stated that they used placebo. However, allocation concealment was unclear. Only one trial reported any patient deaths. No significant improvement in mortality was identified (odds ratio (OR) 0.42, 95% confidence interval (CI) 0.10 to 1.76). Improvements in serum markers of liver inflammation and liver histology were identified. Potentially prognostically linked markers such as bilirubin and albumin were incompletely reported. Bone mineral density (weighted mean difference -2.84%, 95% CI -4.16 to -1.53) and the number of patients with any adverse event (OR 8.99, 95% CI 2.15 to 37.58) were significantly increased in the glucocorticosteroid group.

Authors' conclusions: There is insufficient data to support or reject the use of glucocorticosteroids for patients with primary biliary cirrhosis. It may be appropriate to consider a large prospective randomised clinical trial on this topic.

PubMed Disclaimer

Conflict of interest statement

None known.

Figures

1.1
1.1. Analysis
Comparison 1 Glucocorticosteroids versus placebo/no intervention ‐ efficacy, Outcome 1 Mortality.
1.2
1.2. Analysis
Comparison 1 Glucocorticosteroids versus placebo/no intervention ‐ efficacy, Outcome 2 Liver transplanation.
1.3
1.3. Analysis
Comparison 1 Glucocorticosteroids versus placebo/no intervention ‐ efficacy, Outcome 3 Mortality or liver transplantation.
1.4
1.4. Analysis
Comparison 1 Glucocorticosteroids versus placebo/no intervention ‐ efficacy, Outcome 4 Liver‐related mortality.
1.5
1.5. Analysis
Comparison 1 Glucocorticosteroids versus placebo/no intervention ‐ efficacy, Outcome 5 No. developing jaundice.
1.6
1.6. Analysis
Comparison 1 Glucocorticosteroids versus placebo/no intervention ‐ efficacy, Outcome 6 No. with a doubling of s‐bilirubin.
1.7
1.7. Analysis
Comparison 1 Glucocorticosteroids versus placebo/no intervention ‐ efficacy, Outcome 7 No. developing ascites.
1.8
1.8. Analysis
Comparison 1 Glucocorticosteroids versus placebo/no intervention ‐ efficacy, Outcome 8 No. developing portal hypertension.
1.9
1.9. Analysis
Comparison 1 Glucocorticosteroids versus placebo/no intervention ‐ efficacy, Outcome 9 No. developing hepatic encephalopathy.
1.10
1.10. Analysis
Comparison 1 Glucocorticosteroids versus placebo/no intervention ‐ efficacy, Outcome 10 Dichotomous histology variables.
1.11
1.11. Analysis
Comparison 1 Glucocorticosteroids versus placebo/no intervention ‐ efficacy, Outcome 11 Albumin (g/L) % change around 1 year.
1.12
1.12. Analysis
Comparison 1 Glucocorticosteroids versus placebo/no intervention ‐ efficacy, Outcome 12 Alkaline phosphatases (IU/L) % change around 1 year.
1.13
1.13. Analysis
Comparison 1 Glucocorticosteroids versus placebo/no intervention ‐ efficacy, Outcome 13 Aspatate transaminase (IU/L) % change around 1 year.
1.14
1.14. Analysis
Comparison 1 Glucocorticosteroids versus placebo/no intervention ‐ efficacy, Outcome 14 Bilirubin (mmol/L) % change around 1 year.
1.15
1.15. Analysis
Comparison 1 Glucocorticosteroids versus placebo/no intervention ‐ efficacy, Outcome 15 IgG (g/L) % change around 1 year.
1.16
1.16. Analysis
Comparison 1 Glucocorticosteroids versus placebo/no intervention ‐ efficacy, Outcome 16 IgM (g/L) % change around 1 year.
2.1
2.1. Analysis
Comparison 2 Glucocorticosteroids versus placebo/no intervention ‐ adverse events, Outcome 1 No. with fragility fracture.
2.2
2.2. Analysis
Comparison 2 Glucocorticosteroids versus placebo/no intervention ‐ adverse events, Outcome 2 Bone mineral density.
2.3
2.3. Analysis
Comparison 2 Glucocorticosteroids versus placebo/no intervention ‐ adverse events, Outcome 3 No. clincally Cushingoid.
2.4
2.4. Analysis
Comparison 2 Glucocorticosteroids versus placebo/no intervention ‐ adverse events, Outcome 4 No. with weight gain over 2.5 kg.
2.5
2.5. Analysis
Comparison 2 Glucocorticosteroids versus placebo/no intervention ‐ adverse events, Outcome 5 Any reported adverse event.
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD003778

References

References to studies included in this review

Frankfurt 1999 {published data only (unpublished sought but not used)}
    1. Leuschner M, Maier KP, Schitling J, Stefan S, Herrmann G, Dahm HH, et al. Oral budesonide and ursodeoxycholic acid for treatment of primary biliary cirrhosis: results of a prospective double‐blind trial. Gastroenterology 1999;117(10):918‐25. - PubMed
    1. Leuschner M, Maier KP, Schitling J, Stefan S, Herrmann G, Dahm HH, et al. Ursodeoxycholic acid (UDCA) and budesonide (BUD) in the treatment of primary biliary cirrhosis (PBC). A prospective double‐blind trial. Hepatology 1999;30(4 Pt 2):471A. - PubMed
    1. Leuschner M, Maier KP, Schitling J, Strahl R, Herrmann G, Dahm HH, et al. Ursodeoxycholic acid (UDCA) and budesonide (BUD) is superior to UDCA monotherapy in primary biliary cirrhosis (PBC). Journal of Hepatology 1999;30(1):GS4/20.
    1. Leuschner U, Maier KP, Guldutuna S, Parte‐Peterhans S, Leuschner M. Ursodeoxycholic acid in combination with prednisolone or budenoside in therapy of primary biliary cirrhosis. Falk Symposium 93. Dodecht: Kluwer, 1997:299‐302.
    1. Leuscner U, Maier P, Schitling J, Strahl R, Herrmann G, Leuschner M. Ursodeoxycholic acid and budenoside in the treatment of primary biliary cirrhosis. XV International Bile Acid Meeting Bile Acids and Cholestasis. 1998; Vol. Falk Symposium 108:60‐1.
Newcastle 1989 {published and unpublished data}
    1. Combes B. Prednisolone for primary biliary cirrhosis ‐ good news, bad news. Hepatology 1989;10(4):511‐3. - PubMed
    1. Mitchison HC, Bassendine MF, Malcolm AJ, Watson AJ, Record CO, James OF. A pilot double blind controlled trial of prednisolone treatment in primary biliary cirrhosis (PBC) [EASL abstract]. Journal of Hepatology 1986;3(Supp 1):S28.
    1. Mitchison HC, Bassendine MF, Malcolm AJ, Watson AJ, Record CO, James OF. A pilot, double‐blind, controlled 1‐year trial of prednisolone treatment in primary biliary cirrhosis: hepatic improvement but greater bone loss. Hepatology 1989;10(4):420‐9. - PubMed
    1. Mitchison HC, Bassendine MF, Watson AJ, Record CO, James OF. Double blind placebo‐controlled trial of prednisolone treatment in primary biliary cirrhosis (PBC): a 3 year update [EASL abstract]. Journal of Hepatology 1989;9:4. - PubMed
    1. Mitchison HC, Palmer JM, Bassendine MF, Watson AJ, Record CO, James OF. A controlled trial of prednisolone treatment in primary biliary cirrhosis. Three‐year results. Journal of Hepatology 1992;15(3):336‐44. - PubMed

References to studies excluded from this review

Beukers 1988 {published data only}
    1. Beukers R, Schalm SW. Effect of cyclosporin and cyclosporin and prenisolone in primary biliary cirrhosis. Transplant Proceedings 1988;20(Suppl 4):340‐3. - PubMed
    1. Beukers R, Schalm SW. Immunosuppressive therapy for primary biliary cirrhosis. Journal of Hepatology 1992;14(1):1‐6. - PubMed
Carman 1955 {published data only}
    1. Carman CT, Giansiruca JE. Effect of steroid theraapy on the clinical and laboraoty features in primary biliary cirrhosis. Gastroenterology 1955;28(2):193‐215. - PubMed
Fracchia 2000 {published data only}
    1. Fracchia M, Secreto P, Tabone M, Zaffino C, Pera A, Galatola G. Serum interferon gamma in primary bilary cirrhosis: effect of ursodeoxycholic acid and prednisolone therapy alone and in combination. EJGH 2000;121:463‐88. - PubMed
Hempfling 2003 {published data only}
    1. Elias E. Ursodeoxycholic acid and budesonide for PBC. Unexpected risks and benefits. Hepatology 2003;38:541.
    1. Hempfling W, Grunhage, F, Dilger K, Reichel C, Beuers U, Sauerbrach T. Pharmacokinetics and pharmacodynamic action of budesonide in early stage primary biliary cirrhosis. Hepatology. 2002; Vol. 36, issue 2:422A. - PubMed
    1. Hempfling W, Grunhage, F, Dilger K, Reichel C, Beuers U, Sauerbrach T. Pharmacokinetics and pharmodynamic action of budesonide in early and late stage PBC. Hepatology 2003;38:196‐202. - PubMed
    1. Hempfling W, Grunhage, F, Dilger K, Reichel C, Beuers U, Sauerbrach T. Portal vein thrombosis in patients with late stage primary biliary cirrhosis treated with budesonide. Hepatology 2002;36(2):423A. - PubMed
Leuschner 1996 {published data only}
    1. Leuschner M. Ursodeoxycholic acid in combination with prednisolone. Progress in Hepatopharmacology 1997;2(1):79‐90.
    1. Leuschner M, Guldutuna S, You T, Hubner K, Bhatti S, Leuschner U. Ursodeoxycholic acid and prednisolone versus ursodeoxycholic acid and placebo in the treatment of early stages of primary biliary cirrhosis. Journal of Hepatology 1996;25(1):49‐57. - PubMed
    1. Leuschner U, Maier KP, Guldutuna S, Parte‐Peterhans S, Leuschner M. Ursodeoxycholic acid in combination with prednisolone or budenoside in therapy of primary biliary cirrhosis. Falk Symposium 93 1997;1:299‐302.
Mayo 1951 {published data only}
    1. Butt HR, Comfort MW, Power MH, Mason HL. Observations on the effect of cortisone acetate in two pateints with hepatic disease. Journal of Laboratory and Clincal Medicine 1951;37:870‐84. - PubMed
Mayo 1972 {published data only}
    1. Baggenstoss AH, Soloway RD, nSummerskill WHJ, Elveback LR, Schoenfield LJ. Chronic acitve liver disease. Range of histologic lesions and thier response to treatment and evolution. Human Pathology 1972;3(2):183‐98. - PubMed
    1. Uribe M, Wolf AM, Summerskill WHJ. Steroid side effect during therapy of chronic liver disease; what to expect. Gastroenterology 1976;71(5):932.
Mayo 2000 {published data only}
    1. Angulo P, Jorgenesen RA, Keach JC, Dickson ER, Smith C, Lindor KD. Oral budesonide in the treatment of patients with a suboptimal response to UDCA. Hepatology 2000;31:318‐23. - PubMed
    1. Angulo P, Smith C, Jorgenesen RA, Keach JC, Dickson ER, Lindor KD. Budesonide in the treatment of patients with a suboptimal response to UDCA. Hepatology 1999;30(4 Pt 2):471A. - PubMed
Okamota 1999 {published data only}
    1. Okamoto R, Yamamoto K, Yabushita K, Matsumura S, Snimda N, Okano N, Tsuli T. Prednisolone treatment changes T‐cell reptiore in primary biliary cirrhosis. Clonal analysis of T cell receptor. Hepatology 1999;30(4 Pt 2):471A.
Taal 1985 {published data only}
    1. Taal BG, Schalm, SW. Cryoglobulins in primary biliary cirrhosis: prevalence and modulation by immunosuppressive therapy. Zeitschrift für Gastroenterologie 1985;23:228‐34. - PubMed
van Berkum 1990 {published data only}
    1. Berkum FNR, Beukers R, Birkenhager JC, Kooij PPM, Schalm SW, Pols HAP. Bone mass in women with primary biliary cirrhosis. The relation with histological stage and use of glucocorticoids. Gastroenterology 1990;99:1134‐9. - PubMed
Wilson 1958 {published data only}
    1. Howat HT, Ralston AJ, Varley H, Wilson JAC. The late results of long term treatment of primary biliary cirrhosis by corticosteroids. Revue Internationale d Hepatologie 1966;16:227‐38. - PubMed
    1. Wilson JAC, Short IA, Varley H, Howat HT. The biochemical changes induced by corticosteroids in xanthomatous biliary cirrhosis. Gastroenterolgia 1958;89:343‐5. - PubMed
Wolfhagen 1994 {published data only}
    1. Wolfhagen FH, Buuren HR, Schalm SW. Combined treatment with ursodeoxycholic acid and prednisone in primary biliary cirrhosis. Netherlands Journal of Medicine 1993;43:A9. - PubMed
    1. Wolfhagen FH, Buuren HR, Schalm SW. Combined treatment with ursodeoxycholic acid and prednisone in primary biliary cirrhosis. Netherlands Journal of Medicine 1994;44(3):84‐9. - PubMed
Wolfhagen 1998 {published data only}
    1. Lim AG, Wolfhagen FHJ, Verma A, Buuren HR, Jazrawi RP, Levy JH, et al. Soluble intercellular adhesion molecule‐1 in primary biliary cirrhosis: effect of ursodeoxycholic acid and immunosuppressive therapy. EJHG 1997;9(2):155‐61. - PubMed
    1. Lim AG, Wolfhagen FHJ, Verma A, Buuren HR, Jazrawi RP, Levy JH, et al. Soluble intercellular adhesion molecule‐1 in primary biliary cirrhosis: effect of ursodeoxycholic acid, prenisolone and azathioprine. Falk Symposium 86. 1995. - PubMed
    1. Burren H, Wolfhagen FHJ, Lim AG, Verma A, Jazrawi RP, Northfield TC, et al. A randomized placebo‐controlled trial with prednisone/azathioprine in addition to ursodeoxycholic acid in primary biliary cirrhosis. Falk Symposium 75. 1995.
    1. Wolfhagen FH, Buuren HR, Ouden JW, Hop WC, Leeuwen JP, Schalm SW, et al. Cyclical etidronate in the prevention of bone loss in corticosteroid‐treated primary biliary cirrhosis. A prospective, controlled pilot study. Journal of Hepatology 1997;26(2):325‐30. - PubMed
    1. Wolfhagen FH, Hoogstraten HJ, Buuren HR, Berge Henegouwen GP, Kate FJ, Hop WC, et al. Triple therapy with ursodeoxycholic acid, prednisone and azathioprine in primary biliary cirrhosis: a 1‐year randomized, placebo‐controlled study. Journal of Hepatology 1998;29(5):736‐42. - PubMed

Additional references

Ahrens 1950
    1. Ahrens E, Payne M, Kunkel H, Eisenmenger E, Blondheim S. Primary biliary cihrrosis. Medicine 1950;29:299‐366. - PubMed
Alderson 2004
    1. Alderson P, Green S, Higgins JPT, editors. Cochrane Reviewers' Handbook 4.2.1. Chichester, UK: John Wiley & Sons, Ltd, 2004.
Atkinson 1956
    1. Atkinson M, Nordin BEC, Sherlock S. Bone disease in obstructive jaundice. Quarterly Journal of Medicine 1956;25:299‐312. - PubMed
Chan 2004
    1. Chan AW, Hrobjartsson A, Haahr MT, Gotzsche PC, Altman DG. Empirical evidence for selective reporting of outcomes in randomized trials: comparison of protocols to published articles. JAMA 2004;291(20):2457‐65. - PubMed
Christensen 1985
    1. Christensen E, Neuberger J, Crowe J, Altman DG, Popper H, Portmann B, et al. Beneficial effect of azathioprine and prediction of prognosis in primary biliary cirrhosis. Final results of an international trial. Gastroenterology 1985;89(5):1084‐91. - PubMed
Combes 1999b
    1. Combes B, Carithers R L, Maddrey WC, Munoz S, Garcia Tsao G, Bonner GF, et al. Biliary bile acids in primary biliary cirrhosis: effect of ursodeoxycholic acid. Hepatology 1999;29(6):1649‐54. - PMC - PubMed
Cupps 1982
    1. Cupps TR, Fauci AS. Coritcosteroid‐mediated immunregulation in man. Immunological reviews 1982;65:133‐55. [MEDLINE: ] - PubMed
DeMets 1987
    1. DeMets DL. Methods of combining randomized clinical trials: strengths and limitations. Statistics in Medicine 1987;6:341‐8. - PubMed
DerSimoian 1986
    1. DerSimonian R, Laird N. Meta‐analysis in clinical trials. Controlled Clinical Trials 1986;7:177‐88. - PubMed
Dickson 1985
    1. Dickson ER, Fleming TR, Wiesner RH, Baldus WP, Fleming CR, Ludwig J, et al. Trial of penicillamine in advanced primary biliary cirrhosis. New England Journal of Medicine 1985;312:1011‐5. - PubMed
Dickson 1989
    1. Dickson ER, Grambsch PM, Fleming TR, Fisher LD, Langworthy A. Prognosis in primary biliary cirrhosis: model for decision making. Hepatology 1989;10:1‐7. - PubMed
Egger 1997
    1. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta‐analysis detected by a simple graphical test. BMJ 1997;315:629‐34. - PMC - PubMed
Epstein 1981
    1. Epstein O, Jain S, Lee RG, Cook DG, Boss AM, Scheuer PJ, et al. D‐penicillamine treatment improves survival in primary biliary cirrhosis. Lancet 1981;1(8233):1275‐7. - PubMed
Gluud 1998
    1. Gluud C. 'Negative trials' are positive!. Journal of Hepatology 1998;28:731‐3. - PubMed
Gluud 1999
    1. Gluud C, Christensen E. Ursodeoxycholic acid for primary biliary cirrhosis (Protocol for a Cochrane Review). The Cochrane Database of Systematic Reviews 1999, Issue 2. - PubMed
Gluud 2001a
    1. Gluud C, Christensen E. Ursodeoxycholic acid for primary biliary cirrhosis (Cochrane Review). The Cochrane Database of Systematic Reviews 2001, Issue 4. - PubMed
Gluud 2001b
    1. Gluud, C, Christensen E. Ursodeoxycholic acid for primary biliary cirrhosis: lesson for the future?. Jounal of Hepatology 2001;34:787‐8. - PubMed
Gong 2004
    1. Gong Y, Gluud C. Colchicine for primary biliary cirrhosis (Cochrane Review). The Cochrane Database of Systematic Reviews 2004, Issue 2. - PubMed
Goulis 1999
    1. Goulis J, Lerandro G, Burroughs A. Randomised controlled trials of ursodeoxycholic‐acid therapy for primary biliary cirrhosis: a meta‐analysis. Lancet 1999;354:1053‐60. - PubMed
Hoofnagle 1986
    1. Hoofnagle JH, Davis GL, Schafer DF, Peters M, Avigan MI, Pappas SC, et al. Randomized trial of chlorambucil for primary biliary cirrhosis. Gastroenterology 1986;91:1327‐34. - PubMed
ICH‐GCP 1997
    1. International Conference on Harmonisation Expert Working Group. Code of Federal Regulations & International Conference on Harmonization Guidelines. Media: Parexel Barnett, 1997.
Kaplan 1986
    1. Kaplan MM, Alling DW, Zimmerman HJ, Wolfe HJ, Sepersky RA, Hirsch GS, et al. A prospective trial of colchicine for primary biliary cirrhosis. New England Journal of Medicine 1986;315:1448‐54. - PubMed
Kaplan 1991
    1. Kaplan MM, Knox TA. Treatment of primary biliary cirrhosis with low‐dose weekly methotrexate. Gastroenterology 1991;101:1332‐8. - PubMed
Kaplan 1996
    1. Kaplan M. Primary biliary cirrhosis. New England Journal of Medicine 1996;335:1570‐80. - PubMed
Kilmurry 1996
    1. Kilmurry MR, Heathcote EJ, Cauch‐Dudek K, O'Rourke K, Bailey RJ, Blendis LM. Is the Mayo model for predicting survival useful after the introduction of ursodeoxycholic acid treatment for primary biliary cirrhosis?. Hepatology 1996;23:1148‐53. - 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. - PubMed
Lindor 1995
    1. Lindor KD, Janes CH, Crippin JS, Jorgensen RA, Dickson ER. Bone disease in primary biliary cirrhosis: does ursodeoxycholic acid make a difference?. Hepatology 1995;21:389‐92. - PubMed
Matloff 1982
    1. Matloff DS, Alpert E, Resnick RH, Kaplan MM. A prospective trial of D‐penicillamine in primary biliary cirrhosis. New England Journal of Medicine 1982;306(6):319‐26. - PubMed
Mitchison 1992
    1. Mitchison HC, Palmer JM, Bassendine MF, Watson AJ, Record CO, James OF. A controlled trial of prednisolone treatment in primary biliary cirrhosis. Three‐year results. Jouranl of Hepatology 1993;15:336‐44. - 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;352:609‐13. - PubMed
Moher 2001
    1. Moher B, Schulz KF, Altam DG. The consort statement revised recommendations for improving the quality of reports of parallel group controlled trials. Lancet 2001;357:1191‐4. - PubMed
Neuberger 1985
    1. Neuberger J, Christensen E, Portmann B, Caballeria J, Rodes J, Ranek L, et al. Double blind controlled trial of D‐penicillamine in patients with primary biliary cirrhosis. Gut 1985;26(2):114‐9. - PMC - PubMed
Newton 2001
    1. Newton J, Francis R, Prince M, James O, Bassendine M, Rawlings D, Jones D. Osteoporosis in primary biliary cirrhosis revisited. Gut 2001;48:282‐7. - PMC - PubMed
Palmer 1999
    1. Palmer JM, Diamond AG, Yeaman SJ, Bassendine MF, Jones DEJ. T cell responses to the putative dominant autoepitope in primary biliary cirrhosis (PBC). Clinical and Experimental Iimmunology 1999;116:133‐9. - PMC - PubMed
Poupon 1999
    1. Poupon, RE, Bonnand AM, Chretien Y, Poupon R. Ten‐year survival in ursodeoxycholic acid‐treated patients with primary biliary cirrhosis. The UDCA‐PBC Study Group. Hepatology 1999;29:1668‐71. - PubMed
Prince 2000
    1. Prince M, Jones D, Metcalf J, Craig W, James O. Symptom development and prognosis of initially asymptomatic PBC. Hepatology 2000;32(4 Pt 2):171A.
Sacks 1987
    1. Sacks HS, Berrier J, Reitman D, Angona‐Berk VA, Chalmers TC. Meta‐analysis of randomised controlled trials. New England Journal of Medicine 1987;19:450‐5. - PubMed
Schluz 1995
    1. Schulz KF, Chalmers I, Haeys RJ, Altman DG. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. Journal of American Medical Association 1995;273:408‐12. - PubMed
Stellon 1985
    1. Stellon AJ, Davies A, Compston J, Williams R. Osteoporosis in chronic liver disease. Quarterly Journal of Medicine 1985;223:783‐90. - PubMed
Verma 1999
    1. Verma A, Jazrawi RP, Ahmed HA, Northfield TC. Prescribing habits in primary biliary cirrhosis: a national survey. European Journal of Gastroenterology and Hepatology 1999;11(8):817‐20. - PubMed
Vuoristo 1995
    1. Vuoristo M, Farkkila M, Karvonen AL, Leino R, Lehtola J, Makinen J, et al. A placebo‐controlled trial of primary biliary cirrhosis treatment with colchicine and ursodeoxycholic acid [see comments]. Gastroenterology 1995;108:1470‐8. - PubMed
Warnes 1987
    1. Warnes TW, Smith A, Lee FI, Haboubi NY, Johnson PJ, Hunt L. A controlled trial of colchicine in primary biliary cirrhosis: trial design and preliminary report. Journal of Hepatology 1987;5:1‐7. - PubMed
Wiesner 1990
    1. Wiesner RH, Ludwig J, Lindor KD, Jorgensen RA, Baldus WP, Homburger HA, et al. A controlled trial of cyclosporine in the treatment of primary biliary cirrhosis. New England Journal of Medicine 1990;322(20):1419‐24. - PubMed

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