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Published on September 24, 2014 | http://doi.org/10.5867/medwave.2014.08.6019

Is ursodeoxycholic acid effective in primary biliary cirrhosis?

¿Es efectivo el ácido ursodeoxicólico en cirrosis biliar primaria?

Gabriel Rada , Macarena Mac-Namara

Abstract

Ursodeoxycholic acid is considered as first line treatment in patients with primary biliary cirrhosis. Its mechanism of action in this disease is unknown and there is controversy about its clinical impact. Searching in Epistemonikos database, which is maintained by screening 19 databases, we identified four systematic reviews including 16 studies. We combined the evidence using tables with summary of findings following the GRADE approach and concluded ursodeoxycholic acid may not have any effect on pruritus, and there is uncertainty about its effect on mortality, need for liver transplantation or on any other important outcome for the patient.

This work is licensed under a Creative Commons Attribution 4.0 International License. Esta licencia permite el uso, distribución y reproducción del artículo en cualquier medio, siempre y cuando se otorgue el crédito correspondiente al autor del artículo y al medio en que se publica, en este caso, Medwave.

Authors

Gabriel Rada

radagabriel@epistemonikos.org

Macarena Mac-Namara

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History

Citation Rada G, Mac-Namara M. Is ursodeoxycholic acid effective in primary biliary cirrhosis?. Medwave 2014;14(08):e6019 doi: 10.5867/medwave.2014.08.6019

Submission date 01/01/1970

Acceptance date 01/01/1970

Publication date 24/09/2014

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References

  1. Gong Y, Huang Z, Christensen E, Gluud C. Ursodeoxycholic acid for patients with primary biliary cirrhosis: an updated systematic review and meta-analysis of randomized clinical trials using Bayesian approach as sensitivity analyses. Am J Gastroenterol. 2007 Aug;102(8):1799-807. | CrossRef | PubMed
  2. Goulis J, Leandro G, Burroughs AK. Randomised controlled trials of ursodeoxycholic-acid therapy for primary biliary cirrhosis: a meta-analysis. Lancet. 1999 Sep 25;354(9184):1053-60. | CrossRef | PubMed
  3. Rudic JS, Poropat G, Krstic MN, Bjelakovic G, Gluud C. Ursodeoxycholic acid for primary biliary cirrhosis. Cochrane Database Syst Rev. 2012 Dec 12;12:CD000551. | CrossRef | PubMed
  4. Shi J, Wu C, Lin Y, Chen YX, Zhu L, Xie WF. Long-term effects of mid-dose ursodeoxycholic acid in primary biliary cirrhosis: a meta-analysis of randomized controlled trials. Am J Gastroenterol. 2006 Jul;101(7):1529-38. | CrossRef | PubMed
  5. A randomised, double-blind, placebo-controlled trial of ursodeoxycholic acid in primary biliary cirrhosis. Bile Acids and the Hepatobiliary System. From Basic Science to Clinical Practice. Falk Symposium 68, 1993
  6. AK B, Arora R, Salen G, O’Brien C, JR S. Effect of ursodiol on biliary bile acid composition and conjugation in patients with primary biliary cirrhosis. Gastroenterology. 1990; 98(5 part2): A567. | Link
  7. Angulo P, Lindor KD, Therneau TM, Jorgensen RA, Malinchoc M, Kamath PS, et al. Utilization of the Mayo risk score in patients with primary biliary cirrhosis receiving ursodeoxycholic acid. Liver. 1999 Apr;19(2):115-21. | PubMed
  8. Arora R, AK B, Salen G, O’Brien C,JR S. Effect of ursodiol on bile acid conjugation in patients with primary biliary cirrhosis. Hepatology, 1990;12(4):994. | CrossRef
  9. Balan V, Dickson ER, Jorgensen RA, Lindor KD. Effect of ursodeoxycholic acid on serum lipids of patients with primary biliary cirrhosis. Mayo Clin Proc. 1994 Oct;69(10):923-9. | PubMed
  10. Calmus Y, Poupon R. Ursodeoxycholic acid (UDCA) in the treatment of chronic cholestatic diseases. Biochimie. 1991 Oct;73(10):1335-8. | PubMed
  11. O'Brian CB, Senior JR, Sternlieb JM, Sample M, Saul SM, Arora R. Ursodiol treatment of primary biliary cirrhosis. Gastroenterology. 1990;98(5 part2):A617. | Link
  12. O'Brian CB , Senior JR , Sternlieb JM , Saul SM. Caution: not all patients with primary biliary cirrhosis may successfully be treated by ursodiol. Second International Meeting on Pathochemistry, Pathophysiology and Pathomechanisms of the Biliary System and New Strategies for the Treatment of Hepato-Biliary Diseases. Bologna, 1990.
  13. Chazouilleres O, Legendre C,Poupon R. Histological course of primary biliary cirrhosis (PBC) treated with ursodeoxycholic acid (UDCA). Hepatology. 1995;22(4 part 2):125A. | CrossRef
  14. CJR G, Hunt L, Smith A, Fallowfield G, Rowan B, TW, W. A trial of ursodeoxycholic acid (UDCA) and colchicine in primary biliary cirrhosis (PBC). Hepatology. 1994;(20):151A.
  15. Combes B. Ursodeoxycholic acid therapy in patients with primary biliary cirrhosis. Hepatology, 1991;(14):91A.
  16. Combes B, Carithers RL Jr, Maddrey WC, Lin D, McDonald MF, Wheeler DE, et al. A randomized, double-blind, placebo-controlled trial of ursodeoxycholic acid in primary biliary cirrhosis. Hepatology. 1995 Sep;22(3):759-66. | PubMed
  17. Combes B, Carithers RL Jr, Maddrey WC, Munoz S, Garcia-Tsao G, Bonner GF, et al. Biliary bile acids in primary biliary cirrhosis: effect of ursodeoxycholic acid. Hepatology. 1999 Jun;29(6):1649-54. | CrossRef | PubMed
  18. Combes B, Carithers RL, Maddrey WC, Munoz SJ, McDonald MF, Garcia-Tsao. The American multicenter primary biliary cirrhosis, Ursodiol versus placebo study group (PUPS) trial. Falk Symposium No. 80. XIII International Bile Acid Meeting. Bile Acids in Gastroenterology: Basic and Clinical Aspects. San Diego, 1994.
  19. Combes B, Carithers RL Jr, 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 Sep;22(3):759-66. | PubMed
  20. Combes B, Carithers RL Jr, Maddrey WC, Lin D, McDonald MF, Wheeler DE, Eigenbrodt EH, et al. A randomised, double-blind, placebo-controlled trial of ursodeoxycholic acid (UDCA) in primary biliary cirrhosis (PBC). Falk Symposium No. 68. XII International Bile Acid Meeting. Bile Acids and the Hepatobiliary System. From Basic Science to Clinical Practice. Basel, 1993b.
  21. Combes B, Markin RS, Wheeler DE, Rubin R, West AB, Mills AS, et al. The effect of ursodeoxycholic acid on the florid duct lesion of primary biliary cirrhosis. Hepatology. 1999 Sep;30(3):602-5. | CrossRef | PubMed
  22. Combes B, Luketic VA, Peters MG, Zetterman RK, Garcia-Tsao G, Munoz SJ, et al. Prolonged follow-up of patients in the U.S. multicenter trial of ursodeoxycholic acid for primary biliary cirrhosis. Am J Gastroenterol. 2004 Feb;99(2):264-8. | PubMed
  23. Corpechot C, Carrat F, Bonnand AM, Poupon RE, Poupon R. The effect of ursodeoxycholic acid therapy on liver fibrosis progression in primary biliary cirrhosis. Hepatology. 2000 Dec;32(6):1196-9. | CrossRef | PubMed
  24. Corpechot C, Carrat F, Bonnand AM, Poupon RE, Poupon, R. A Markov model for assessment of histological progression in PBC provides evidence that UDCA therapy is effective in early stages. Hepatology. 1999;30(4):474A.
  25. Degott C, Zafrani ES, Callard P, Balkau B, Poupon RE, Poupon R. Histopathological study of primary biliary cirrhosis and the effect of ursodeoxycholic acid treatment on histology progression. Hepatology. 1999 Apr;29(4):1007-12. | CrossRef | PubMed
  26. Heathcote EJ, Cauch-Dudek K, Walker V, Bailey RJ, Blendis LM, Ghent CN, et al. The Canadian Multicenter Double-blind Randomized Controlled Trial of ursodeoxycholic acid in primary biliary cirrhosis. Hepatology. 1994 May;19(5):1149-56. | PubMed
  27. Heathcote EJL, Cauch K, Walker V, Bailey RJ, Blendis LM, Ghent CN. A double blind randomised controlled multi-centre trial of ursodeoxycholic acid (UDCA) in primary biliary cirrhosis (PBC): results from a blinded interim analysis. XII International Bile Acid Meeting. Bile Acids and the Hepatobiliary System. From Basic Science to Clinical Practice. Basel. Falk Symposium No. 68, 1992.
  28. Emond M, Carithers RL Jr, Luketic VA, Peters M, Zetterman RK, Garcia-Tsao G. Does ursodeoxycholic acid improve survival in patients with primary biliary cirrhosis? Comparison of outcome in the US multicenter trial to expected survival using the Mayo Clinic prognostic model. Hepatology. 1996;(24):168A.
  29. Dickson ER, Lindor KD. Beneficial effects of ursodeoxycholic acid in an open trial of patients with primary biliary cirrhosis. Bile Acids as Therapeutic Agents. From Basic Science to Clinical Practice. Falk Symposium 58, 1991 .
  30. Dickson ER, Lindor KD, Baldus WP, Jorgensen RA, Ludwig J, Murtaugh PA. Ursodiol (URSO) is effective therapy for patients with primary biliary cirrhosis (PBC). Falk Symposium No. 68. XII International Bile Acid Meeting. Bile Acids and the Hepatobiliary System. From Basic Science to Clinical Practice. Basel, 1992.
  31. Dickson ER , Lindor KD , Baldus WP , Jorgensen RA , Ludwig J , Murtaugh PA. Ursodiol is effective therapy for patients with primary biliary cirrhosis. Bile Acids and the Hepatobiliary System. From Basic Science to Clinical Practice. Falk Symposium 68, 1993.
  32. De la Mora G, Bobadilla J, Romero P, Rodríguez-Leal G, Morán S, Kershenobich D. Does treatment with ursodeoxycholic acid (UDCA) really diminish cholesterol serum levels in primary biliary cirrhosis (PBC)? Hepatology: 1994;(19):57I.
  33. Ghent CN, Cauch-Dudek K, Heathcote EJ. Ursodeoxycholic acid therapy effects on pruritus and fatigue in primary biliary cirrhosis. Hepatology. 1997; 438 A.
  34. Goddard CJR, Smith A, Hunt L, Halder T, Hillier V, Rowan B, Fallowfield G. Surrogate Markers of Response in a Trial of ursodeoxycholic acid (UDCA) and colchine in primary biliary cirrhosis (PBC). Gut. 1995;36(supp 1): A30. | CrossRef
  35. Güldütuna S, Leuschner U, Imhof M, Zimmer G. Treatment of chronic active hepatitis and primary biliary cirrhosis with ursodeoxycholic acid. Z Gastroenterol. 1992 Mar;30 Suppl 1:49-54. | PubMed
  36. Papatheodoridis GV , Deutsch M , Hadziyannis ES , Tzakou A , Hadziyannis SJ. Ursodeoxycholic-acid for primary biliary cirrhosis: final results of a 12-year prospective, randomised, controlled trial. J Hepatol. 2000;32(Suppl 2):40.
  37. Papatheodoridis GV, Hadziyannis ES, Deutsch M, Hadziyannis SJ. Ursodeoxycholic acid for primary biliary cirrhosis: final results of a 12-year, prospective, randomized, controlled trial. Am J Gastroenterol. 2002 Aug;97(8):2063-70. | CrossRef | PubMed
  38. Hadziyannis SJ, Hadziyannis ES, Lianidou E, Makris A. Long-term treatment of primary biliary cirrhosis with ursodeoxycholic acid: the third year of a controlled trial. XI International Bile Acid Meeting. Bile Acids as Therapeutic Agents - From Basic Science to Clinical Practice. Freiburg, 1990.
  39. Hadziyannis S, Hadziyannis E. A randomised controlled trial of ursodeoxycholic acid (UDCA) in primary biliary cirrhosis (PBC). Hepatology. 1988;(8):1421.
  40. Hadziyannis SJ, Hadziyannis ES, Makris AA. Randomised controlled trial of ursodeoxycholic acid (UDCA) in primary biliary cirrhosis (PBC). Hepatology,1989;(10):580.
  41. Heathcote EJL, Cauch K, Walker V, Blendis LM, Pappas SC, Wanless IR . A double-blind randomised controlled multicenter trial of ursodeoxycholic acid in primary biliary cirrhosis: results from a 1991 interim analysis. Bile Acids and the Hepatobiliary System. From Basic Science to Clinical Practice. Falk Symposium 68, 1993.
  42. Heathcote EJL, Cauch K, Walker V, Bailey RJ, Blendis LM, Ghent CN (). The Canadian multi-centre double blind randomised controlled trial of ursodeoxycholic acid in primary biliary cirrhosis. Hepatology. 1992;(16):91A
  43. Heathcote EJL, Cauch K, Walker V, Bailey RJ, Blendis LM, Ghent CN, Pappas SC. A four-year follow-up study of ursodeoxycholic acid therapy for primary biliary cirrhosis. Gastroenterology. 1993;(104):A914.
  44. Turner IB, Myszor M, Mitchison HC, Bennett MK, Burt AD, James OF. A two year controlled trial examining the effectiveness of ursodeoxycholic acid in primary biliary cirrhosis. J Gastroenterol Hepatol. 1994 Mar-Apr;9(2):162-8. | PubMed
  45. Siegel JL, Jorgensen R, Angulo P, Lindor KD. Treatment with ursodeoxycholic acid is associated with weight gain in patients with primary biliary cirrhosis. J Clin Gastroenterol. 2003 Aug;37(2):183-5. | PubMed
  46. Laurin JM, DeSotel CK, Jorgensen RA, Dickson ER, Lindor KD. The natural history of abdominal pain associated with primary biliary cirrhosis. Am J Gastroenterol. 1994 Oct;89(10):1840-3. | PubMed
  47. Jorgensen R, Angulo P, Dickson ER, Lindor KD. Results of long-term ursodiol treatment for patients with primary biliary cirrhosis. Am J Gastroenterol. 2002 Oct;97(10):2647-50. | CrossRef | PubMed
  48. Senior JR, O'Brian CB. Mortality risk indices as outcome measures of the effectiveness of ursodeoxycholic acid treatment of cholestatic liver diseases. Bile Acids as Therapeutic Agents. From Basic Science to Clinical Practice. Falk Symposium 58, 1991.
  49. Senior JR, O'Brian CB, Dickson ER. Effect of oral ursodiol treatment on the predicted probability of mortality in primary biliary cirrhosis. Hepatology. 1990;(12):438.
  50. Lindor KD, Dickson ER, Baldus WP, Jorgensen RA, Ludwig J, Murtaugh PA, et al. Ursodeoxycholic acid in the treatment of primary biliary cirrhosis. Gastroenterology. 1994 May;106(5):1284-90. | PubMed
  51. Lindor KD, Lacerda MA, Jorgensen RA, DeSotel CK, Batta AK, Salen G, et al. Relationship between biliary and serum bile acids and response to ursodeoxycholic acid in patients with primary biliary cirrhosis. Am J Gastroenterol. 1998 Sep;93(9):1498-504. | CrossRef | PubMed
  52. Lindor KD, Jorgensen RA, Therneau TM, Malinchoc M, Dickson ER. Ursodeoxycholic acid delays the onset of esophageal varices in primary biliary cirrhosis. Mayo Clin Proc. 1997 Dec;72(12):1137-40. | CrossRef | PubMed
  53. Lindor KD , Therneau TM , Jorgensen RA , Malinchoc M , Dickson ER. Effects of ursodeoxycholic acid (UDCA) on survival in patients with primary biliary cirrhosis (PBC). Gastroenterology. 1995;108(4):A1111.
  54. Lindor KD, Therneau TM, Jorgensen RA, Malinchoc M, Dickson ER. Effects of ursodeoxycholic acid on survival in patients with primary biliary cirrhosis. Gastroenterology. 1996 May;110(5):1515-8. | PubMed | Link
  55. Lindor KD, Baldus WP, Jorgensen RA, Ludwig J, Murtaugh PA, Dickson ER. Ursodeoxycholic acid (UDCA) is beneficial therapy for patients with primary biliary cirrhosis (PBC). Hepatology, 1992;(16):91A.
  56. Kisand KE, Karvonen AL, Vuoristo M, Färkkilä M, Lehtola J, Inkovaara J, et al. Ursodeoxycholic acid treatment lowers the serum level of antibodies against pyruvate dehydrogenase and influences their inhibitory capacity for the enzyme complex in patients with primary biliary cirrhosis. J Mol Med (Berl). 1996 May;74(5):269-72. | PubMed
  57. Batts KP, Jorgensen RA, Dickson ER, Hofmann AF , Rossi SS , Ludwig J. The effects of ursodeoxycholic acid on hepatic inflammation and histological stage in patients with primary biliary cirrhosis. Hepatology.1993;(18):175A.
  58. Batts KP, Jorgensen RA, Dickson ER, Lindor KD. Effects of ursodeoxycholic acid on hepatic inflammation and histological stage in patients with primary biliary cirrhosis. Am J Gastroenterol. 1996 Nov;91(11):2314-7. | PubMed
  59. Leuschner M , Fischer H , Güldütuna S , Kurtz W , Gatzen MAU - , Hellstern A. Does ursodeoxycholic acid (UDCA) influence cell membrane architecture in patients with primary biliary cirrhosis (PBC)? Gastroenterology. 1989;(96):A621.
  60. Leuschner M, Fischer H, Hübner K, Güldütuna S, Gatzen MAU, Hellstern A. Ursodeoxycholic acid (UDCA) treatment of primary biliary cirrhosis: clinical and histological results of a controlled study. Trends in Bile Acid Research. Falk Symposium 52, 1989.
  61. Leuschner M, Güldütuna S, Imhof M, Bhati S, You T, Leuschner U. Ursodeoxycholic acid therapy in primary biliary cirrhosis. Bile Acids and the Hepatobiliary System. From Basic Science to Clinical Practice. Falk Symposium 68, 1993.
  62. Leuschner U, Fischer H, Hübner K. [Ursodeoxycholic acid in the treatment of primary biliary cirrhosis: results of a controlled study]. Z Gastroenterol Verh. 1989 Jul;24:133. | PubMed
  63. Leuschner U, Fischer H, Kurtz W, Güldütuna S, Hübner K, Hellstern A, et al. Ursodeoxycholic acid in primary biliary cirrhosis: results of a controlled double-blind trial. Gastroenterology. 1989 Nov;97(5):1268-74. | PubMed
  64. Eriksson LS, Olsson R, Glauman H, Prytz H, Befrits H, Lindgren S. Ursodeoxycholic acid (UDCA) in patients with primary biliary cirrhosis (PBC) Results of a two-year randomised placebo-controlled study. Scandinavian Journal of Gastroenterology. 1995;30(Suppl 209):35.
  65. Eriksson LS, Olsson R, Glauman H, Prytz H, Befrits R, Rydén BO, et al. Ursodeoxycholic acid treatment in patients with primary biliary cirrhosis. A Swedish multicentre, double-blind, randomized controlled study. Scand J Gastroenterol. 1997 Feb;32(2):179-86. | PubMed
  66. Lacerda MA , Lindor KD , Jorgensen RA , Rossi SS , Hofmann AF , Salen GR. Dissimilar patterns of serum and biliary bile acids in primary biliary cirrhosis (PBC) patients treated with ursodeoxycholic acid (UDCA). Hepatology. 1993;18(4):174A.
  67. Neuman MG , Cameron RG , Shear NH , Blendis LM (). Ursodeoxycholic acid reduces fibrosis in primary biliary cirrhosis. XV International Bile Acid Meeting. Bile Acids and Cholestasis. Titisee, Germany. Falk Symposium No 108, 1998.
  68. Michieletti P, Witt-Sullivan H, Steiner G, Cauch K, Walker V, Heathcote EJL. No evidence for a more atherogenic serum lipid profile with ursodeoxycholic acid (UDCA) therapy in patients with primary biliary cirrhosis (PBC). Hepatology. 1993;18(4):217A.
  69. Kilmurry MR, Cauch-Dudek K, O`Rourke K, Heathcote EJ. Is the Mayo model useful for predicting survival following the introduction of ursodeoxycholic acid treatment for primary biliary cirrhosis? Gastroenterology. 1995;108(Suppl 4):96.
  70. Kilmurry MR, Heathcote EJ, Cauch-Dudek K, O'Rourke K, Bailey RJ, Blendis LM, et al. Is the Mayo model for predicting survival useful after the introduction of ursodeoxycholic acid treatment for primary biliary cirrhosis? Hepatology. 1996 May;23(5):1148-53. | CrossRef | PubMed
  71. Myszor M, Turner I, Mitshison H, Bennett M , Burt AD , James OFW. No symptomatic or histological benefit from ursodeoxycholic acid treatment in PBC after 1 year. Controlled pilot study. Hepatology. 1990;(12):415.
  72. Oka H, Toda G, Ikeda Y, Hashimoto N, Hasumura Y, Kamimura T, et al. A multi-center double-blind controlled trial of ursodeoxycholic acid for primary biliary cirrhosis. Gastroenterol Jpn. 1990 Dec;25(6):774-80. | PubMed
  73. Pares, A. Long-term treatment of primary biliary cirrhosis with ursodeoxycholic acid: results of a randomised, double-blind, placebo-controlled trial. Journal of Hepatology. 1997;26(Suppl 1):166.
  74. Pares A, Caballeria L, Bruguera M, Rodes J. Factors influencing histological progression of early primary biliary cirrhosis. Effect of ursodeoxycholic acid. Journal of Hepatology. 2001;34(Suppl 1): 189-190.
  75. Pares A, Caballeria L, Rodes. Long-term ursodeoxycholic acid treatment delays progression of mild primary biliary cirrhosis. J Hepatol. 2001;34(Suppl 1):187–188. | CrossRef
  76. Parés A, Caballería L, Rodés J, Bruguera M, Rodrigo L, García-Plaza A, et al. Long-term effects of ursodeoxycholic acid in primary biliary cirrhosis: results of a double-blind controlled multicentric trial. UDCA-Cooperative Group from the Spanish Association for the Study of the Liver. J Hepatol. 2000 Apr;32(4):561-6. | CrossRef | PubMed
  77. Italian Multicenter Project for UDCA Treatment in PBC. Ursodeoxycholic acid (UDCA) for symptomatic primary biliary cirrhosis (PBC): A double-blind multicenter trial. J Hepatol. 1989;(9):S44.
  78. Battezzati PM, Podda M, Bianchi FB, Naccarato R, Orlandi F, Surrenti C,et al. Ursodeoxycholic acid for symptomatic primary biliary cirrhosis. Preliminary analysis of a double-blind multicenter trial. Italian Multicenter Group for the Study of UDCA in PBC. J Hepatol. 1993 Mar;17(3):332-8. | PubMed
  79. Huet PM, Huet J, Hotte S. Long term effect of ursodeoxycholic acid (UDCA) on hepatic function and portal hypertension in primary biliary cirrhosis (PBC). Hepatology, 1994;(20):202A.
  80. Huet PM, Willems B, Huet J, Poupon R. Effects of ursodeoxycholic acid (UDCA) on hepatic function and portal hypertension in primary biliary cirrhosis (PBC). Hepatology. 1990;(12):907.
  81. Huet PM, Willems B, Huet J, Poupon R. Effects of ursodeoxycholic acid (UDCA) on hepatic function and portal hypertension in primary biliary cirrhosis (PBC). XII International Bile Acid Meeting. Bile Acids and the Hepatobiliary System. From Basic Science to Clinical Practice. Basel. Falk Symposium No. 68, 1992.
  82. Podda M, Almasio P, Battezzati PM, Crosignani A. Long-term effect of the administration of ursodeoxycholic acid alone or with colchicine in patients with primary biliary cirrhosis: a double-blind multicenter study. Bile Acids and the Hepatobiliary System. From Basic Science to Clinical Practice. Falk Symposium 68, 1993.
  83. Podda MPM, Battezzati A, Crosignani FB, Bianchi M, Fusconi M, Chiaramonte A. Ursodeoxycholic acid (UDCA) for symptomatic primary biliary cirrhosis (PBC): a double-blind multicenter trial. J Hepatol. 1989;(Suppl 1):S44. | CrossRef
  84. Poupon R. Ursodeoxycholic acid in the treatment of primary biliary cirrhosis. First International Symposium. Trends and Discovery in Bile Acid Research. Bora-Bora (French Polynesia), 1990.
  85. Poupon R, Chazouillères O, Balkau B, Poupon RE. Clinical and biochemical expression of the histopathological lesions of primary biliary cirrhosis. UDCA-PBC Group. J Hepatol. 1999;30(3):408-412.
  86. Poupon R, Poupon RE. Ursodeoxycholic acid for primary biliary cirrhosis. International Lugano Symposium on Biliary Physiology and Diseases: Strategies for the Treatment of Hepatobiliary Diseases. Lugano. Falk Symposium No. 53, 1989.
  87. Poupon R, Poupon R. Ursodeoxycholic acid in the treatment of primary biliary cirrhosis. Strategies for the Treatment of Hepatobiliary Diseases. Falk Symposium 53, 1990.
  88. Jorgensen RA, Dickson ER, Hofmann AF, Rossi SS, Lindor KD. Characterisation of patients with a complete biochemical response to ursodeoxycholic acid. Gut. 1995 Jun;36(6):935-8. | PubMed | Link
  89. Poupon RE, Balkau B, Eschwège 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 May 30;324(22):1548-54. | CrossRef | PubMed
  90. Poupon RE, Balkau B, Eschwege E, Poupon R, Kaplan MM. A multicenter, controlled trial of ursodiol for the treatment of primary biliary cirrhosis. Ann Int Med. 1991;115(6 Suppl 2):48.
  91. Poupon RE, Balkau B, Guéchot J, Heintzmann F. Predictive factors in ursodeoxycholic acid-treated patients with primary biliary cirrhosis: role of serum markers of connective tissue. Hepatology. 1994 Mar;19(3):635-40.
  92. Poupon RE , Balkau B , Poupon R. Beneficial effect of ursodeoxycholic acid (UDCA) in primary biliary cirrhosis (PBC). Final results of the French Canadian trial. Hepatology. 1990;(12):872.
  93. Poupon RE , Chretien Y , Balkau B , Niard AM , Poupon R (1992). Ursodeoxycholic therapy for primary biliary cirrhosis: a four year controlled study. Hepatology. 1992;(16):91A.
  94. Poupon RE, Chrétien Y, Poupon R, Paumgartner G. Serum bile acids in primary biliary cirrhosis: effect of ursodeoxycholic acid therapy. Hepatology. 1993 Apr;17(4):599-604. | PubMed
  95. Poupon RE, 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. | PubMed
  96. Poupon RE, Ouguerram K, Chrétien Y, Verneau C, Eschwège E, Magot T, et al. Cholesterol-lowering effect of ursodeoxycholic acid in patients with primary biliary cirrhosis. Hepatology. 1993 Apr;17(4):577-82. | PubMed
  97. Poupon RE, Poupon R. Ursodeoxycholic acid (UDCA) for treatment of primary biliary cirrhosis (PBC). Interim analysis of a double-blind multicenter randomised trial. Hepatology. 1989;(10):639.
  98. Poupon RE, Poupon R, Balkau B. Ursodiol for the long-term treatment of primary biliary cirrhosis. The UDCA-PBC Study Group. N Engl J Med. 1994 May 12;330(19):1342-7. | CrossRef | PubMed
  99. Carithers RL , Luketic VA , Peters M , Zetterman RK , Garcia-Tsao G (). Extended follow-up of patients in the U.S. multicenter trial of ursodeoxycholic acid for primary biliary cirrhosis. Gastroenterology. 1996;110(4):A1163.
  100. Hwang SJ, Chan CY, Lee SD, Wu JC, Tsay SH, Lo KJ. Ursodeoxycholic acid in the treatment of primary biliary cirrhosis: a short-term, randomized, double-blind controlled, cross-over study with long-term follow up. J Gastroenterol Hepatol. 1993 May-Jun;8(3):217-23. | PubMed
  101. Hadziyannis S. Long-term treatment of primary biliary cirrhosis with ursodeoxycholic acid: the third year of a controlled trial. Bile Acids as Therapeutic Agents. From Basic Science to Clinical Practice. Falk Symposium 58, 1990.
  102. Hadziyannis SJ, Hadziyannis ES, Makris A. A randomised controlled trial of Ursodeoxyccholic acid (UDCA) in primary biliary cirrhosis (PBC). Eur J Clin Invest. 1989;19(Pt 2):A15.
  103. Miettinen TA, Farkkila M, Vuoristo M, Karvonen AL, Leino R, Lehtola J. Improvement of serum non cholesterol sterols may indicate retarded progression of primary biliary cirrhosis (PBC) in a randomised placebo controlled two-year trial with colchicine and ursodeoxycholic acid. Gastroenterology. 1993;(104):A954.
  104. Miettinen TA, Färkkilä M, Vuoristo M, Karvonen AL, Leino R, Lehtola J, et al. Serum cholestanol, cholesterol precursors, and plant sterols during placebo-controlled treatment of primary biliary cirrhosis with ursodeoxycholic acid or colchicine. Hepatology. 1995 May;21(5):1261-8. | PubMed
  105. Zukowski TH, Jorgensen RA, Dickson ER, Lindor KD. Autoimmune conditions associated with primary biliary cirrhosis: response to ursodeoxycholic acid therapy. Am J Gastroenterol. 1998 Jun;93(6):958-61. | CrossRef | PubMed
  106. Toda G, Oka H, Hasumura Y, Kamimura T, Ohat Y, Tsuji T. A multicenter double-blind controlled trial of ursodeoxycholic acid for primary biliary cirrhosis in Japan. XI International Bile Acid Meeting. Bile Acids as Therapeutic Agents - From Basic Science to Clinical Practice. Freiburg, 1990.
  107. Vuoristo M, Färkkilä M, Karvonen AL, Leino R, Lehtola J, Mäkinen J, et al. A placebo-controlled trial of primary biliary cirrhosis treatment with colchicine and ursodeoxycholic acid. Gastroenterology. 1995 May;108(5):1470-8. | PubMed
  108. Vuoristo M, Färkkilä M, Gylling H, Karvonen AL, Leino R, Lehtola J, et al. Expression and therapeutic response related to apolipoprotein E polymorphism in primary biliary cirrhosis. J Hepatol. 1997 Jul;27(1):136-42. | CrossRef | PubMed
  109. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of cholestatic liver diseases. J Hepatol. 2009 Aug;51(2):237-67. | CrossRef
  110. Lindor KD, Gershwin ME, Poupon R, Kaplan M, Bergasa NV, Heathcote EJ; American Association for Study of Liver Diseases. Primary biliary cirrhosis. Hepatology. 2009 Jul;50(1):291-308. | CrossRef