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Overview of the treatment of primary biliary cholangitis (primary biliary cirrhosis)

Author
Raoul Poupon, MD
Section Editor
Keith D Lindor, MD
Deputy Editor
Anne C Travis, MD, MSc, FACG, AGAF

INTRODUCTION

Primary biliary cholangitis (PBC; previously referred to as primary biliary cirrhosis) is characterized by an ongoing immunologic attack on the intralobular bile ducts that eventually leads to cirrhosis and liver failure. The terminology was changed from primary biliary cirrhosis to primary biliary cholangitis to more accurately describe the disorder and its natural history [1]. The prognosis of patients with PBC has improved greatly during the past two decades because of its diagnosis at earlier stages and the widespread use of ursodeoxycholic acid as treatment. As a result, far fewer patients require liver transplantation, and patients with stages I and II PBC appear to have a normal life expectancy. (See "Pathogenesis of primary biliary cholangitis (primary biliary cirrhosis)" and "Clinical manifestations, diagnosis, and prognosis of primary biliary cholangitis (primary biliary cirrhosis)" and "Liver transplantation in primary biliary cholangitis (primary biliary cirrhosis)".)

The management of PBC has two goals:

Treatment of the symptoms and complications that result from chronic cholestasis

Suppression of the underlying pathogenic process: the destruction of small intralobular hepatic bile ducts

The treatment of PBC will be reviewed here. The pathogenesis and diagnosis of PBC, as well as the general management of patients with cirrhosis, are discussed elsewhere. (See "Pathogenesis of primary biliary cholangitis (primary biliary cirrhosis)" and "Clinical manifestations, diagnosis, and prognosis of primary biliary cholangitis (primary biliary cirrhosis)" and "Cirrhosis in adults: Overview of complications, general management, and prognosis".)

                            

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Literature review current through: Nov 2016. | This topic last updated: Wed Oct 19 00:00:00 GMT+00:00 2016.
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References
Top
  1. Beuers U, Gershwin ME, Gish RG, et al. Changing nomenclature for PBC: From 'cirrhosis' to 'cholangitis'. Hepatology 2015; 62:1620.
  2. Lindor KD, Gershwin ME, Poupon R, et al. Primary biliary cirrhosis. Hepatology 2009; 50:291.
  3. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of cholestatic liver diseases. J Hepatol 2009; 51:237.
  4. Lanspa SJ, Chan AT, Bell JS 3rd, et al. Pathogenesis of steatorrhea in primary biliary cirrhosis. Hepatology 1985; 5:837.
  5. Levy C, Lindor KD. Management of osteoporosis, fat-soluble vitamin deficiencies, and hyperlipidemia in primary biliary cirrhosis. Clin Liver Dis 2003; 7:901.
  6. Phillips JR, Angulo P, Petterson T, Lindor KD. Fat-soluble vitamin levels in patients with primary biliary cirrhosis. Am J Gastroenterol 2001; 96:2745.
  7. Kaplan MM, Elta GH, Furie B, et al. Fat-soluble vitamin nutriture in primary biliary cirrhosis. Gastroenterology 1988; 95:787.
  8. Kaplan MM, Goldberg MJ, Matloff DS, et al. Effect of 25-hydroxyvitamin D3 on vitamin D metabolites in primary biliary cirrhosis. Gastroenterology 1981; 81:681.
  9. Elta GH, Sepersky RA, Goldberg MJ, et al. Increased incidence of hypothyroidism in primary biliary cirrhosis. Dig Dis Sci 1983; 28:971.
  10. Schussler GC, Schaffner F, Korn F. Increased serum thyroid hormone binding and decreased free hormone in chronic active liver disease. N Engl J Med 1978; 299:510.
  11. AHRENS EH Jr, PAYNE MA, KUNKEL HG, et al. Primary biliary cirrhosis. Medicine (Baltimore) 1950; 29:299.
  12. Cohen LB, Ambinder EP, Wolke AM, et al. Role of plasmapheresis in primary biliary cirrhosis. Gut 1985; 26:291.
  13. Thornton JR, Triger DR, Losowsky MS. Variceal bleeding is associated with reduced risk of severe cholestasis in primary biliary cirrhosis. Q J Med 1989; 71:467.
  14. Navasa M, Parés A, Bruguera M, et al. Portal hypertension in primary biliary cirrhosis. Relationship with histological features. J Hepatol 1987; 5:292.
  15. Nakanuma Y, Ohta G. Nodular hyperplasia of the liver in primary biliary cirrhosis of early histological stages. Am J Gastroenterol 1987; 82:8.
  16. Boyer TD, Kokenes DD, Hertzler G, et al. Effect of distal splenorenal shunt on survival of patients with primary biliary cirrhosis. Hepatology 1994; 20:1482.
  17. Pells G, Mells GF, Carbone M, et al. The impact of liver transplantation on the phenotype of primary biliary cirrhosis patients in the UK-PBC cohort. J Hepatol 2013; 59:67.
  18. Theal JJ, Toosi MN, Girlan L, et al. A randomized, controlled crossover trial of ondansetron in patients with primary biliary cirrhosis and fatigue. Hepatology 2005; 41:1305.
  19. Kaplan MM, Bonis PA. Modafinil for the treatment of fatigue in primary biliary cirrhosis. Ann Intern Med 2005; 143:546.
  20. Ian Gan S, de Jongh M, Kaplan MM. Modafinil in the treatment of debilitating fatigue in primary biliary cirrhosis: a clinical experience. Dig Dis Sci 2009; 54:2242.
  21. Jones DE, Newton JL. An open study of modafinil for the treatment of daytime somnolence and fatigue in primary biliary cirrhosis. Aliment Pharmacol Ther 2007; 25:471.
  22. Corpechot C, Abenavoli L, Rabahi N, et al. Biochemical response to ursodeoxycholic acid and long-term prognosis in primary biliary cirrhosis. Hepatology 2008; 48:871.
  23. Shibata J, Fujiyama S, Honda Y, Sato T. Combination therapy with ursodeoxycholic acid and colchicine for primary biliary cirrhosis. J Gastroenterol Hepatol 1992; 7:277.
  24. Almasio PL, Floreani A, Chiaramonte M, et al. Multicentre randomized placebo-controlled trial of ursodeoxycholic acid with or without colchicine in symptomatic primary biliary cirrhosis. Aliment Pharmacol Ther 2000; 14:1645.
  25. Battezzati PM, Zuin M, Crosignani A, et al. Ten-year combination treatment with colchicine and ursodeoxycholic acid for primary biliary cirrhosis: a double-blind, placebo-controlled trial on symptomatic patients. Aliment Pharmacol Ther 2001; 15:1427.
  26. Combes B, Emerson SS, Flye NL, et al. Methotrexate (MTX) plus ursodeoxycholic acid (UDCA) in the treatment of primary biliary cirrhosis. Hepatology 2005; 42:1184.
  27. Jones EA, ten Kate FJ, ter Borg F, et al. Combination therapy with mycophenolate mofetil and ursodeoxycholic acid for primary biliary cirrhosis. Eur J Gastroenterol Hepatol 1999; 11:1165.
  28. Jones EA. Rationale for trials of long-term mycophenolate mofetil therapy for primary biliary cirrhosis. Hepatology 2002; 35:258.
  29. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm503964.htm (Accessed on June 01, 2016).
  30. Kowdley KV, Luketic VA, Jones DE, et al. The first new monotherapy therapeutic PBC study in a decade? An international study evaluating the farnesoid X receptor agonist obeticholic acid in PBC. Hepatology 2011; 54:416A.
  31. Hirschfield GM, Mason A, Luketic V, et al. Efficacy of obeticholic acid in patients with primary biliary cirrhosis and inadequate response to ursodeoxycholic acid. Gastroenterology 2015; 148:751.
  32. Nevens F, Andreone P, Mazzella G, et al. A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis. N Engl J Med 2016; 375:631.
  33. Kaplan MM. Primary biliary cirrhosis. N Engl J Med 1996; 335:1570.
  34. Van Norstrand MD, Malinchoc M, Lindor KD, et al. Quantitative measurement of autoantibodies to recombinant mitochondrial antigens in patients with primary biliary cirrhosis: relationship of levels of autoantibodies to disease progression. Hepatology 1997; 25:6.
  35. Kim WR, Poterucha JJ, Jorgensen RA, et al. Does antimitochondrial antibody status affect response to treatment in patients with primary biliary cirrhosis? Outcomes of ursodeoxycholic acid therapy and liver transplantation. Hepatology 1997; 26:22.
  36. Wangoo A, Haynes AR, Sutcliffe SP, et al. Modulation of platelet-derived growth factor B mRNA abundance in macrophages by colchicine and dibutyryl-cAMP. Mol Pharmacol 1992; 42:584.
  37. Kershenobich D, Rojkind M, Quiroga A, Alcocer-Varela J. Effect of colchicine on lymphocyte and monocyte function and its relation to fibroblast proliferation in primary biliary cirrhosis. Hepatology 1990; 11:205.
  38. Miller LC, Kaplan MM. Serum interleukin-2 and tumor necrosis factor-alpha in primary biliary cirrhosis: decrease by colchicine and relationship to HLA-DR4. Am J Gastroenterol 1992; 87:465.
  39. Kaplan MM, Alling DW, Zimmerman HJ, et al. A prospective trial of colchicine for primary biliary cirrhosis. N Engl J Med 1986; 315:1448.
  40. Warnes TW, Smith A, Lee FI, et al. A controlled trial of colchicine in primary biliary cirrhosis. Trial design and preliminary report. J Hepatol 1987; 5:1.
  41. Bodenheimer H Jr, Schaffner F, Pezzullo J. Evaluation of colchicine therapy in primary biliary cirrhosis. Gastroenterology 1988; 95:124.
  42. Zifroni A, Schaffner F. Long-term follow-up of patients with primary biliary cirrhosis on colchicine therapy. Hepatology 1991; 14:990.
  43. Gong Y, Gluud C. Colchicine for primary biliary cirrhosis: a Cochrane Hepato-Biliary Group systematic review of randomized clinical trials. Am J Gastroenterol 2005; 100:1876.
  44. Vuoristo M, Färkkilä M, Karvonen AL, et al. A placebo-controlled trial of primary biliary cirrhosis treatment with colchicine and ursodeoxycholic acid. Gastroenterology 1995; 108:1470.
  45. Miettinen TA, Färkkilä M, Vuoristo M, et al. Serum cholestanol, cholesterol precursors, and plant sterols during placebo-controlled treatment of primary biliary cirrhosis with ursodeoxycholic acid or colchicine. Hepatology 1995; 21:1261.
  46. Knox TA, Kaplan MM. Treatment of primary sclerosing cholangitis with oral methotrexate. Am J Gastroenterol 1991; 86:546.
  47. Wiesner RH, LaRusso NF, Ludwig J, Dickson ER. Comparison of the clinicopathologic features of primary sclerosing cholangitis and primary biliary cirrhosis. Gastroenterology 1985; 88:108.
  48. Cronstein BN, Naime D, Ostad E. The antiinflammatory mechanism of methotrexate. Increased adenosine release at inflamed sites diminishes leukocyte accumulation in an in vivo model of inflammation. J Clin Invest 1993; 92:2675.
  49. Weigand K, Zaugg PY, Frei A, Zimmermann A. Long-term follow-up of serum N-terminal propeptide of collagen type III levels in patients with chronic liver disease. Hepatology 1984; 4:835.
  50. Weinstein GD, Jeffes E, McCullough JL. Cytotoxic and immunologic effects of methotrexate in psoriasis. J Invest Dermatol 1990; 95:49S.
  51. Segal R, Yaron M, Tartakovsky B. Methotrexate: mechanism of action in rheumatoid arthritis. Semin Arthritis Rheum 1990; 20:190.
  52. Suarez CR, Pickett WC, Bell DH, et al. Effect of low dose methotrexate on neutrophil chemotaxis induced by leukotriene B4 and complement C5a. J Rheumatol 1987; 14:9.
  53. Kaplan MM, Knox TA. Treatment of primary biliary cirrhosis with low-dose weekly methotrexate. Gastroenterology 1991; 101:1332.
  54. Kaplan MM, DeLellis RA, Wolfe HJ. Sustained biochemical and histologic remission of primary biliary cirrhosis in response to medical treatment. Ann Intern Med 1997; 126:682.
  55. Kaplan MM, Schmid C, Provenzale D, et al. A prospective trial of colchicine and methotrexate in the treatment of primary biliary cirrhosis. Gastroenterology 1999; 117:1173.
  56. Bonis PA, Kaplan M. Methotrexate improves biochemical tests in patients with primary biliary cirrhosis who respond incompletely to ursodiol. Gastroenterology 1999; 117:395.
  57. Buscher HP, Zietzschmann Y, Gerok W. Positive responses to methotrexate and ursodeoxycholic acid in patients with primary biliary cirrhosis responding insufficiently to ursodeoxycholic acid alone. J Hepatol 1993; 18:9.
  58. Babatin MA, Sanai FM, Swain MG. Methotrexate therapy for the symptomatic treatment of primary biliary cirrhosis patients, who are biochemical incomplete responders to ursodeoxycholic acid therapy. Aliment Pharmacol Ther 2006; 24:813.
  59. Hendrickse MT, Rigney E, Giaffer MH, et al. Low-dose methotrexate is ineffective in primary biliary cirrhosis: long-term results of a placebo-controlled trial. Gastroenterology 1999; 117:400.
  60. Lindor KD, Dickson ER, Jorgensen RA, et al. The combination of ursodeoxycholic acid and methotrexate for patients with primary biliary cirrhosis: the results of a pilot study. Hepatology 1995; 22:1158.
  61. Bach N, Bodian C, Bodenheimer H, et al. Methotrexate therapy for primary biliary cirrhosis. Am J Gastroenterol 2003; 98:187.
  62. Giljaca V, Poropat G, Stimac D, Gluud C. Methotrexate for primary biliary cirrhosis. Cochrane Database Syst Rev 2010; :CD004385.
  63. Kaplan MM, Cheng S, Price LL, Bonis PA. A randomized controlled trial of colchicine plus ursodiol versus methotrexate plus ursodiol in primary biliary cirrhosis: ten-year results. Hepatology 2004; 39:915.
  64. Kaplan MM, Bonder A, Ruthazer R, Bonis PA. Methotrexate in patients with primary biliary cirrhosis who respond incompletely to treatment with ursodeoxycholic acid. Dig Dis Sci 2010; 55:3207.
  65. Leung J, Bonis PA, Kaplan MM. Colchicine or methotrexate, with ursodiol, are effective after 20 years in a subset of patients with primary biliary cirrhosis. Clin Gastroenterol Hepatol 2011; 9:776.
  66. Mitchison HC, Palmer JM, Bassendine MF, et al. A controlled trial of prednisolone treatment in primary biliary cirrhosis. Three-year results. J Hepatol 1992; 15:336.
  67. Christensen E, Neuberger J, Crowe J, et al. Beneficial effect of azathioprine and prediction of prognosis in primary biliary cirrhosis. Final results of an international trial. Gastroenterology 1985; 89:1084.
  68. Gong Y, Christensen E, Gluud C. Azathioprine for primary biliary cirrhosis. Cochrane Database Syst Rev 2007; :CD006000.
  69. Gong Y, Klingenberg SL, Gluud C. Systematic review and meta-analysis: D-Penicillamine vs. placebo/no intervention in patients with primary biliary cirrhosis--Cochrane Hepato-Biliary Group. Aliment Pharmacol Ther 2006; 24:1535.
  70. Minuk GY, Bohme CE, Burgess E, et al. Pilot study of cyclosporin A in patients with symptomatic primary biliary cirrhosis. Gastroenterology 1988; 95:1356.
  71. Wiesner RH, Ludwig J, Lindor KD, et al. A controlled trial of cyclosporine in the treatment of primary biliary cirrhosis. N Engl J Med 1990; 322:1419.
  72. Lombard M, Portmann B, Neuberger J, et al. Cyclosporin A treatment in primary biliary cirrhosis: results of a long-term placebo controlled trial. Gastroenterology 1993; 104:519.
  73. Gong Y, Christensen E, Gluud C. Cyclosporin A for primary biliary cirrhosis. Cochrane Database Syst Rev 2007; :CD005526.
  74. Angulo P, Patel T, Jorgensen RA, et al. Silymarin in the treatment of patients with primary biliary cirrhosis with a suboptimal response to ursodeoxycholic acid. Hepatology 2000; 32:897.
  75. Leuschner M, Maier KP, Schlichting J, et al. Oral budesonide and ursodeoxycholic acid for treatment of primary biliary cirrhosis: results of a prospective double-blind trial. Gastroenterology 1999; 117:918.
  76. Rautiainen H, Kärkkäinen P, Karvonen AL, et al. Budesonide combined with UDCA to improve liver histology in primary biliary cirrhosis: a three-year randomized trial. Hepatology 2005; 41:747.
  77. Yano K, Kato H, Morita S, et al. Is bezafibrate histologically effective for primary biliary cirrhosis? Am J Gastroenterol 2002; 97:1075.
  78. Kurihara T, Niimi A, Maeda A, et al. Bezafibrate in the treatment of primary biliary cirrhosis: comparison with ursodeoxycholic acid. Am J Gastroenterol 2000; 95:2990.
  79. Nakai S, Masaki T, Kurokohchi K, et al. Combination therapy of bezafibrate and ursodeoxycholic acid in primary biliary cirrhosis: a preliminary study. Am J Gastroenterol 2000; 95:326.
  80. Levy C, Peter JA, Nelson DR, et al. Pilot study: fenofibrate for patients with primary biliary cirrhosis and an incomplete response to ursodeoxycholic acid. Aliment Pharmacol Ther 2011; 33:235.
  81. Iwasaki S, Ohira H, Nishiguchi S, et al. The efficacy of ursodeoxycholic acid and bezafibrate combination therapy for primary biliary cirrhosis: A prospective, multicenter study. Hepatol Res 2008; 38:557.
  82. Ohira H, Sato Y, Ueno T, Sata M. Fenofibrate treatment in patients with primary biliary cirrhosis. Am J Gastroenterol 2002; 97:2147.
  83. Nakamuta M, Enjoji M, Kotoh K, et al. Long-term fibrate treatment for PBC. J Gastroenterol 2005; 40:546.
  84. Cheung AC, Lapointe-Shaw L, Kowgier M, et al. Combined ursodeoxycholic acid (UDCA) and fenofibrate in primary biliary cholangitis patients with incomplete UDCA response may improve outcomes. Aliment Pharmacol Ther 2016; 43:283.
  85. Rabahi N, Chrétien Y, Gaouar F, et al. Triple therapy with ursodeoxycholic acid, budesonide and mycophenolate mofetil in patients with features of severe primary biliary cirrhosis not responding to ursodeoxycholic acid alone. Gastroenterol Clin Biol 2010; 34:283.
  86. Mason AL, Farr GH, Xu L, et al. Pilot studies of single and combination antiretroviral therapy in patients with primary biliary cirrhosis. Am J Gastroenterol 2004; 99:2348.
  87. Lytvyak E, Montano-Loza AJ, Mason AL. Combination antiretroviral studies for patients with primary biliary cirrhosis. World J Gastroenterol 2016; 22:349.
  88. Mason AL, Lindor KD, Bacon BR, et al. Clinical trial: randomized controlled study of zidovudine and lamivudine for patients with primary biliary cirrhosis stabilized on ursodiol. Aliment Pharmacol Ther 2008; 28:886.