Treatment of Primary Biliary Cirrhosis: Therapy with Choleretic and Immunosuppressive Agents

Clinics in Liver Disease

Volumn 12, Issue 2, 2008, Pages 425-443

  Silveira, Marina G ^a   Lindor, Keith D ^a  

^a MAYO CLINIC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALENDRONIC ACID; AZATHIOPRINE; BISPHOSPHONIC ACID DERIVATIVE; BUDESONIDE; CHLORAMBUCIL; CHOLERETIC AGENT; CORTICOSTEROID; CYCLOSPORIN; IMMUNOSUPPRESSIVE AGENT; METHOTREXATE; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; PLACEBO; PREDNISOLONE; PREDNISONE; RALOXIFENE; RIFAMPICIN; RITUXIMAB; SULINDAC; TACROLIMUS; URSODEOXYCHOLIC ACID;

ALOPECIA; AUTOIMMUNE DISEASE; BILIARY CIRRHOSIS; BIOCHEMISTRY; BONE MARROW DEPRESSION; BONE MARROW SUPPRESSION; CLINICAL TRIAL; COST EFFECTIVENESS ANALYSIS; CREATININE BLOOD LEVEL; DIARRHEA; DISEASE COURSE; DRUG BINDING; DRUG DOSE COMPARISON; DRUG DOSE REDUCTION; DRUG FATALITY; DRUG MEGADOSE; DRUG METABOLISM; DRUG RECEPTOR BINDING; DRUG RESPONSE; DRUG TOLERANCE; DRUG WITHDRAWAL; FATIGUE; FLATULENCE; HAIR LOSS; HISTOLOGY; HUMAN; LIFE EXPECTANCY; LIVER FAILURE; LIVER TRANSPLANTATION; LONG TERM CARE; LOW DRUG DOSE; MOUTH ULCER; NONHUMAN; PATIENT COMPLIANCE; PNEUMATOSIS INTESTINALIS; PORTAL HYPERTENSION; PRURITUS; REVIEW; SIDE EFFECT; SURVIVAL; TREATMENT DURATION; TREATMENT RESPONSE; UNSPECIFIED SIDE EFFECT; WEIGHT GAIN;

CHOLAGOGUES AND CHOLERETICS; HUMANS; IMMUNOSUPPRESSIVE AGENTS; LIVER CIRRHOSIS, BILIARY; URSODEOXYCHOLIC ACID;

EID: 43049083346     PISSN: 10893261     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.cld.2008.02.008     Document Type: Review

References (112)

1. Talwalkar J.A., and Lindor K.D. Primary biliary cirrhosis. Lancet 362 9377 (2003) 53-61
2. Lazaridis K.N., and Talwalkar J.A. Clinical epidemiology of primary biliary cirrhosis: incidence, prevalence, and impact of therapy. J Clin Gastroenterol 41 5 (2007) 494-500
3. Kim W.R., Lindor K.D., Locke III G.R., et al. Epidemiology and natural history of primary biliary cirrhosis in a US community. Gastroenterology 119 6 (2000) 1631-1636
4. Scheuer P.J. Ludwig Symposium on biliary disorders-part II. Pathologic features and evolution of primary biliary cirrhosis and primary sclerosing cholangitis. Mayo Clin Proc 73 2 (1998) 179-183
5. Kaplan M.M., and Gershwin M.E. Primary biliary cirrhosis. N Engl J Med 353 12 (2005) 1261-1273
6. Christensen E., Crowe J., Doniach D., et al. Clinical pattern and course of disease in primary biliary cirrhosis based on an analysis of 236 patients. Gastroenterology 78 2 (1980) 236-246
7. Dickson E.R., Grambsch P.M., Fleming T.R., et al. Prognosis in primary biliary cirrhosis: model for decision making. Hepatology 10 1 (1989) 1-7
8. Prince M., Chetwynd A., Newman W., et al. Survival and symptom progression in a geographically based cohort of patients with primary biliary cirrhosis: follow-up for up to 28 years. Gastroenterology 123 4 (2002) 1044-1051
9. Markus B.H., Dickson E.R., Grambsch P.M., et al. Efficiency of liver transplantation in patients with primary biliary cirrhosis. N Engl J Med 320 26 (1989) 1709-1713
10. Lindor K. Ursodeoxycholic acid for the treatment of primary biliary cirrhosis. N Engl J Med 357 15 (2007) 1524-1529
11. Lindor K.D., Dickson E.R., Baldus W.P., et al. Ursodeoxycholic acid in the treatment of primary biliary cirrhosis. Gastroenterology 106 5 (1994) 1284-1290
12. Lindor K.D., Therneau T.M., Jorgensen R.A., et al. Effects of ursodeoxycholic acid on survival in patients with primary biliary cirrhosis. Gastroenterology 110 5 (1996) 1515-1518
13. Poupon R.E., Lindor K.D., Cauch-Dudek K., et al. Combined analysis of randomized controlled trials of ursodeoxycholic acid in primary biliary cirrhosis. Gastroenterology 113 3 (1997) 884-890
14. Angulo P., Lindor K.D., Therneau T.M., et al. Utilization of the Mayo risk score in patients with primary biliary cirrhosis receiving ursodeoxycholic acid. Liver 19 2 (1999) 115-121
15. Corpechot C., Carrat F., Bahr A., et al. The effect of ursodeoxycholic acid therapy on the natural course of primary biliary cirrhosis. Gastroenterology 128 2 (2005) 297-303
16. ter Borg P.C., Schalm S.W., Hansen B.E., et al. Prognosis of ursodeoxycholic Acid-treated patients with primary biliary cirrhosis. Results of a 10-yr cohort study involving 297 patients. Am J Gastroenterol 101 9 (2006) 2044-2050
17. Heathcote E.J. Management of primary biliary cirrhosis. The American Association for the Study of Liver Diseases practice guidelines. Hepatology 31 4 (2000) 1005-1013
18. Leuschner U., Leuschner M., Sieratzki J., et al. Gallstone dissolution with ursodeoxycholic acid in patients with chronic active hepatitis and two years follow-up. A pilot study. Dig Dis Sci 30 7 (1985) 642-649
19. Poupon R., Chretien Y., Poupon R.E., et al. Is ursodeoxycholic acid an effective treatment for primary biliary cirrhosis?. Lancet 1 8537 (1987) 834-836
20. Lazaridis K.N., Gores G.J., and Lindor K.D. Ursodeoxycholic acid 'mechanisms of action and clinical use in hepatobiliary disorders'. J Hepatol 35 1 (2001) 134-146
21. Paumgartner G., and Beuers U. Ursodeoxycholic acid in cholestatic liver disease: mechanisms of action and therapeutic use revisited. Hepatology 36 3 (2002) 525-531
22. Bachrach W.H., and Hofmann A.F. Ursodeoxycholic acid in the treatment of cholesterol cholelithiasis. Part II. Dig Dis Sci 27 9 (1982) 833-856
23. Podda M., Ghezzi C., Battezzati P.M., et al. Effect of different doses of ursodeoxycholic acid in chronic liver disease. Dig Dis Sci 34 12 Suppl (1989) 59S-65S
24. Jorgensen R.A., Dickson E.R., Hofmann A.F., et al. Characterisation of patients with a complete biochemical response to ursodeoxycholic acid. Gut 36 6 (1995) 935-938
25. van de Meeberg P.C., Wolfhagen F.H., Van Berge-Henegouwen G.P., et al. Single or multiple dose ursodeoxycholic acid for cholestatic liver disease: biliary enrichment and biochemical response. J Hepatol 25 6 (1996) 887-894
26. Angulo P., Dickson E.R., Therneau T.M., et al. Comparison of three doses of ursodeoxycholic acid in the treatment of primary biliary cirrhosis: a randomized trial. J Hepatol 30 5 (1999) 830-835
27. Poupon R.E., Balkau B., Eschwege E., et al. A multicenter, controlled trial of ursodiol for the treatment of primary biliary cirrhosis. UDCA-PBC Study Group. N Engl J Med 324 22 (1991) 1548-1554
28. Heathcote E.J., Cauch-Dudek K., Walker V., et al. The Canadian Multicenter Double-blind Randomized Controlled Trial of ursodeoxycholic acid in primary biliary cirrhosis. Hepatology 19 5 (1994) 1149-1156
29. Combes B., Carithers Jr. R.L., Maddrey W.C., et al. A randomized, double-blind, placebo-controlled trial of ursodeoxycholic acid in primary biliary cirrhosis. Hepatology 22 3 (1995) 759-766
30. Jorgensen R., Angulo P., Dickson E.R., et al. Results of long-term ursodiol treatment for patients with primary biliary cirrhosis. Am J Gastroenterol 97 10 (2002) 2647-2650
31. Vuoristo M., Farkkila M., Karvonen A.L., et al. A placebo-controlled trial of primary biliary cirrhosis treatment with colchicine and ursodeoxycholic acid. Gastroenterology 108 5 (1995) 1470-1478
32. Pares A., Caballeria L., Rodes J., 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 32 4 (2000) 561-566
33. Zukowski T.H., Jorgensen R.A., Dickson E.R., et al. Autoimmune conditions associated with primary biliary cirrhosis: response to ursodeoxycholic acid therapy. Am J Gastroenterol 93 6 (1998) 958-961
34. Lindor K.D., Janes C.H., Crippin J.S., et al. Bone disease in primary biliary cirrhosis: does ursodeoxycholic acid make a difference?. Hepatology 21 2 (1995) 389-392
35. Thornton J.R., Triger D.R., and Losowsky M.S. Variceal bleeding is associated with reduced risk of severe cholestasis in primary biliary cirrhosis. Q J Med 71 265 (1989) 467-471
36. Gores G.J., Wiesner R.H., Dickson E.R., et al. Prospective evaluation of esophageal varices in primary biliary cirrhosis: development, natural history, and influence on survival. Gastroenterology 96 6 (1989) 1552-1559
37. Lindor K.D., Jorgensen R.A., Therneau T.M., et al. Ursodeoxycholic acid delays the onset of esophageal varices in primary biliary cirrhosis. Mayo Clin Proc 72 12 (1997) 1137-1140
38. Chan C.W., Gunsar F., Feudjo M., et al. Long-term ursodeoxycholic acid therapy for primary biliary cirrhosis: a follow-up to 12 years. Aliment Pharmacol Ther 21 3 (2005) 217-226
39. Batts K.P., Jorgensen R.A., Dickson E.R., et al. Effects of ursodeoxycholic acid on hepatic inflammation and histological stage in patients with primary biliary cirrhosis. Am J Gastroenterol 91 11 (1996) 2314-2317
40. Combes B., Markin R.S., Wheeler D.E., et al. The effect of ursodeoxycholic acid on the florid duct lesion of primary biliary cirrhosis. Hepatology 30 3 (1999) 602-605
41. Locke III G.R., Therneau T.M., Ludwig J., et al. Time course of histological progression in primary biliary cirrhosis. Hepatology 23 1 (1996) 52-56
42. Angulo P., Batts K.P., Therneau T.M., et al. Long-term ursodeoxycholic acid delays histological progression in primary biliary cirrhosis. Hepatology 29 3 (1999) 644-647
43. Corpechot C., Carrat F., Bonnand A.M., et al. The effect of ursodeoxycholic acid therapy on liver fibrosis progression in primary biliary cirrhosis. Hepatology 32 6 (2000) 1196-1199
44. Poupon R.E., Lindor K.D., Pares A., et al. Combined analysis of the effect of treatment with ursodeoxycholic acid on histologic progression in primary biliary cirrhosis. J Hepatol 39 1 (2003) 12-16
45. Heathcote E.J. Evidence-based therapy of primary biliary cirrhosis. Eur J Gastroenterol Hepatol 11 6 (1999) 607-615
46. Paumgartner G. Ursodeoxycholic acid for primary biliary cirrhosis: treat early to slow progression. J Hepatol 39 1 (2003) 112-114
47. Leuschner U., Guldutuna S., Imhof M., et al. Effects of ursodeoxycholic acid after 4 to 12 years of therapy in early and late stages of primary biliary cirrhosis. J Hepatol 21 4 (1994) 624-633
48. Pares A., Caballeria L., and Rodes J. Excellent long-term survival in patients with primary biliary cirrhosis and biochemical response to ursodeoxycholic Acid. Gastroenterology 130 3 (2006) 715-720
49. Poupon R.E., Bonnand A.M., Chretien Y., et al. Ten-year survival in ursodeoxycholic acid-treated patients with primary biliary cirrhosis. The UDCA-PBC Study Group. Hepatology 29 6 (1999) 1668-1671
50. Jackson H., Solaymani-Dodaran M., Card T.R., et al. Influence of ursodeoxycholic acid on the mortality and malignancy associated with primary biliary cirrhosis: a population-based cohort study. Hepatology 46 4 (2007) 1131-1137
51. Papatheodoridis G.V., Hadziyannis E.S., Deutsch M., et al. Ursodeoxycholic acid for primary biliary cirrhosis: final results of a 12-year, prospective, randomized, controlled trial. Am J Gastroenterol 97 8 (2002) 2063-2070
52. Combes B., Luketic V.A., Peters M.G., et al. Prolonged follow-up of patients in the U.S. multicenter trial of ursodeoxycholic acid for primary biliary cirrhosis. Am J Gastroenterol 99 2 (2004) 264-268
53. Corpechot C., and Poupon R. Geotherapeutics of primary biliary cirrhosis: bright and sunny around the Mediterranean but still cloudy and foggy in the United Kingdom. Hepatology 46 4 (2007) 963-965
54. Goulis J., Leandro G., and Burroughs A.K. Randomised controlled trials of ursodeoxycholic-acid therapy for primary biliary cirrhosis: a meta-analysis. Lancet 354 9184 (1999) 1053-1060
55. Gong Y., Huang Z., Christensen E., et al. 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 102 8 (2007) 1799-1807
56. Gluud C., and Christensen E. Ursodeoxycholic acid for primary biliary cirrhosis. Cochrane Database Syst Rev 1 (2002) CD000551
57. Simko V., Michael S., and Prego V. Ursodeoxycholic therapy in chronic liver disease: a meta-analysis in primary biliary cirrhosis and in chronic hepatitis. Am J Gastroenterol 89 3 (1994) 392-398
58. Lindor K.D., Poupon R., Heathcote E.J., et al. Ursodeoxycholic acid for primary biliary cirrhosis. Lancet 355 9204 (2000) 657-658
59. Shi J., Wu C., Lin Y., et al. Long-term effects of mid-dose ursodeoxycholic acid in primary biliary cirrhosis: a meta-analysis of randomized controlled trials. Am J Gastroenterol 101 7 (2006) 1529-1538
60. Liermann Garcia R.F., Evangelista Garcia C., McMaster P., et al. Transplantation for primary biliary cirrhosis: retrospective analysis of 400 patients in a single center. Hepatology 33 1 (2001) 22-27
61. Lee J., Belanger A., Friedman S., et al. Transplantation among primary biliary cirrhosis patients from 1995 to 2004. Hepatology 44 S1 (2006) A628
62. Pasha T., Heathcote J., Gabriel S., et al. Cost-effectiveness of ursodeoxycholic acid therapy in primary biliary cirrhosis. Hepatology 29 1 (1999) 21-26
63. Leuschner M., Dietrich C.F., You T., et al. Characterisation of patients with primary biliary cirrhosis responding to long term ursodeoxycholic acid treatment. Gut 46 1 (2000) 121-126
64. Angulo P., Jorgensen R.A., and Lindor K.D. Incomplete response to ursodeoxycholic acid in primary biliary cirrhosis: is a double dosage worthwhile?. Am J Gastroenterol 96 11 (2001) 3152-3157
65. Corpechot C., Ping C., Wendum D., et al. Identification of a novel 974C→G nonsense mutation of the MRP2/ABCC2 gene in a patient with Dubin-Johnson syndrome and analysis of the effects of rifampicin and ursodeoxycholic acid on serum bilirubin and bile acids. Am J Gastroenterol 101 10 (2006) 2427-2432
66. Marschall H.U., Wagner M., Zollner G., et al. Complementary stimulation of hepatobiliary transport and detoxification systems by rifampicin and ursodeoxycholic acid in humans. Gastroenterology 129 2 (2005) 476-485
67. Hoensch H.P., Balzer K., Dylewizc P., et al. Effect of rifampicin treatment on hepatic drug metabolism and serum bile acids in patients with primary biliary cirrhosis. Eur J Clin Pharmacol 28 4 (1985) 475-477
68. Ghent C.N., and Carruthers S.G. Treatment of pruritus in primary biliary cirrhosis with rifampin. Results of a double-blind, crossover, randomized trial. Gastroenterology 94 2 (1988) 488-493
69. Bachs L., Pares A., Elena M., et al. Comparison of rifampicin with phenobarbitone for treatment of pruritus in biliary cirrhosis. Lancet 1 8638 (1989) 574-576
70. Podesta A., Lopez P., Terg R., et al. Treatment of pruritus of primary biliary cirrhosis with rifampin. Dig Dis Sci 36 2 (1991) 216-220
71. Bachs L., Pares A., Elena M., et al. Effects of long-term rifampicin administration in primary biliary cirrhosis. Gastroenterology 102 6 (1992) 2077-2080
72. Prince M.I., Burt A.D., and Jones D.E. Hepatitis and liver dysfunction with rifampicin therapy for pruritus in primary biliary cirrhosis. Gut 50 3 (2002) 436-439
73. Batta A.K., Salen G., Pamukcu R., et al. Sulindac and its sulfone derivative inhibit colon cancer via modification of intestinal bile acids. Gastroenterology 110 4 Suppl (1996) A490
74. Leuschner M., Holtmeier J., Ackermann H., et al. The influence of sulindac on patients with primary biliary cirrhosis that responds incompletely to ursodeoxycholic acid: a pilot study. Eur J Gastroenterol Hepatol 14 12 (2002) 1369-1376
75. Broderick A.L., Hofmann A.F., and Carey M.C. Correcting biliary phenotype in cystic fibrosis mice: norursodeoxycholic acid but not UDCA normalizes hepatic bile pH and increases bile flow in G1551D CF mice. Hepatology 36 4 Part 2 (2002) 337A
76. Fickert P., Wagner M., Marschall H.U., et al. 24-norUrsodeoxycholic acid is superior to ursodeoxycholic acid in the treatment of sclerosing cholangitis in Mdr2 (Abcb4) knockout mice. Gastroenterology 130 2 (2006) 465-481
77. Mitchison H.C., Palmer J.M., Bassendine M.F., et al. A controlled trial of prednisolone treatment in primary biliary cirrhosis. Three-year results. J Hepatol 15 3 (1992) 336-344
78. Danielsson A., and Prytz H. Oral budesonide for treatment of autoimmune chronic active hepatitis. Aliment Pharmacol Ther 8 6 (1994) 585-590
79. Angulo P., Jorgensen R.A., Keach J.C., et al. Oral budesonide in the treatment of patients with primary biliary cirrhosis with a suboptimal response to ursodeoxycholic acid. Hepatology 31 2 (2000) 318-323
80. Wolfhagen F.H., van Hoogstraten H.J., van Buuren H.R., et al. Triple therapy with ursodeoxycholic acid, prednisone and azathioprine in primary biliary cirrhosis: a 1-year randomized, placebo-controlled study. J Hepatol 29 5 (1998) 736-742
81. Leuschner M., Maier K.P., Schlichting J., et al. Oral budesonide and ursodeoxycholic acid for treatment of primary biliary cirrhosis: results of a prospective double-blind trial. Gastroenterology 117 4 (1999) 918-925
82. Rautiainen H., Karkkainen P., Karvonen A.L., et al. Budesonide combined with UDCA to improve liver histology in primary biliary cirrhosis: a three-year randomized trial. Hepatology 41 4 (2005) 747-752
83. Ishibashi H., Komori A., Shimoda S., et al. Guidelines for therapy of autoimmune liver disease. Semin Liver Dis 27 2 (2007) 214-226
84. Heathcote J., Ross A., and Sherlock S. A prospective controlled trial of azathioprine in primary biliary cirrhosis. Gastroenterology 70 5 Pt 1 (1976) 656-660
85. Crowe J., Christensen E., Smith M., et al. Azathioprine in primary biliary cirrhosis: a preliminary report of an international trial. Gastroenterology 78 5 Pt 1 (1980) 1005-1010
86. 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 89 5 (1985) 1084-1091
87. Hoofnagle J.H., Davis G.L., Schafer D.F., et al. Randomized trial of chlorambucil for primary biliary cirrhosis. Gastroenterology 91 6 (1986) 1327-1334
88. Zein C.O., Jorgensen R.A., Clarke B., et al. Alendronate improves bone mineral density in primary biliary cirrhosis: a randomized placebo-controlled trial. Hepatology 42 4 (2005) 762-771
89. Levy C., Harnois D.M., Angulo P., et al. Raloxifene improves bone mass in osteopenic women with primary biliary cirrhosis: results of a pilot study. Liver Int 25 1 (2005) 117-121
90. Wolfhagen F.H., van Buuren H.R., and Schalm S.W. Combined treatment with ursodeoxycholic acid and prednisone in primary biliary cirrhosis. Neth J Med 44 3 (1994) 84-90
91. Leuschner M., Guldutuna S., You T., et al. Ursodeoxycholic acid and prednisolone versus ursodeoxycholic acid and placebo in the treatment of early stages of primary biliary cirrhosis. J Hepatol 25 1 (1996) 49-57
92. Hamedani R., Feldman R.D., and Feagan B.G. Review article: drug development in inflammatory bowel disease: budesonide-a model of targeted therapy. Aliment Pharmacol Ther 11 Suppl 3 (1997) 98-108
93. Hempfling W., Grunhage F., Dilger K., et al. Pharmacokinetics and pharmacodynamic action of budesonide in early- and late-stage primary biliary cirrhosis. Hepatology 38 1 (2003) 196-202
94. Greenberg G.R., Feagan B.G., Martin F., et al. Oral budesonide for active Crohn's disease. Canadian Inflammatory Bowel Disease Study Group. N Engl J Med 331 13 (1994) 836-841
95. Minuk G.Y., Bohme C.E., Burgess E., et al. Pilot study of cyclosporin A in patients with symptomatic primary biliary cirrhosis. Gastroenterology 95 5 (1988) 1356-1363
96. Wiesner R.H., Ludwig J., Lindor K.D., et al. A controlled trial of cyclosporine in the treatment of primary biliary cirrhosis. N Engl J Med 322 20 (1990) 1419-1424
97. Lombard M., Portmann B., Neuberger J., et al. Cyclosporin A treatment in primary biliary cirrhosis: results of a long-term placebo controlled trial. Gastroenterology 104 2 (1993) 519-526
98. Bonis P.A., and Kaplan M. Methotrexate improves biochemical tests in patients with primary biliary cirrhosis who respond incompletely to ursodiol. Gastroenterology 117 2 (1999) 395-399
99. Buscher H.P., Zietzschmann Y., and Gerok W. Positive responses to methotrexate and ursodeoxycholic acid in patients with primary biliary cirrhosis responding insufficiently to ursodeoxycholic acid alone. J Hepatol 18 1 (1993) 9-14
100. Babatin M.A., Sanai F.M., and Swain M.G. Methotrexate therapy for the symptomatic treatment of primary biliary cirrhosis patients, who are biochemical incomplete responders to ursodeoxycholic acid therapy. Aliment Pharmacol Ther 24 5 (2006) 813-820
101. Lindor K.D., Dickson E.R., Jorgensen R.A., et al. The combination of ursodeoxycholic acid and methotrexate for patients with primary biliary cirrhosis: the results of a pilot study. Hepatology 22 4 Pt 1 (1995) 1158-1162
102. Gonzalez-Koch A., Brahm J., Antezana C., et al. The combination of ursodeoxycholic acid and methotrexate for primary biliary cirrhosis is not better than ursodeoxycholic acid alone. J Hepatol 27 1 (1997) 143-149
103. Bach N., Bodian C., Bodenheimer H., et al. Methotrexate therapy for primary biliary cirrhosis. Am J Gastroenterol 98 1 (2003) 187-193
104. Hendrickse M.T., Rigney E., Giaffer M.H., et al. Low-dose methotrexate is ineffective in primary biliary cirrhosis: long-term results of a placebo-controlled trial. Gastroenterology 117 2 (1999) 400-407
105. Combes B., Emerson S.S., Flye N.L., et al. Methotrexate (MTX) plus ursodeoxycholic acid (UDCA) in the treatment of primary biliary cirrhosis. Hepatology 42 5 (2005) 1184-1193
106. Sharma A., Provenzale D., McKusick A., et al. Interstitial pneumonitis after low-dose methotrexate therapy in primary biliary cirrhosis. Gastroenterology 107 1 (1994) 266-270
107. Bergasa N.V., Jones A., Kleiner D.E., et al. Pilot study of low dose oral methotrexate treatment for primary biliary cirrhosis. Am J Gastroenterol 91 2 (1996) 295-299
108. Vierling J.M. Future Treatment Options in PBC. Semin Liver Dis 25 3 (2005) 347-363
109. Richardson P.D., James P.D., and Ryder S.D. Mycophenolate mofetil for maintenance of remission in autoimmune hepatitis in patients resistant to or intolerant of azathioprine. J Hepatol 33 3 (2000) 371-375
110. Jones E.A., ten Kate F.J., ter Borg F., et al. Combination therapy with mycophenolate mofetil and ursodeoxycholic acid for primary biliary cirrhosis. Eur J Gastroenterol Hepatol 11 10 (1999) 1165-1169
111. Talwalkar J.A., Angulo P., Keach J.C., et al. Mycophenolate mofetil for the treatment of primary biliary cirrhosis in patients with an incomplete response to ursodeoxycholic acid. J Clin Gastroenterol 39 2 (2005) 168-171
112. Meyers R.P., Shaheen A.A., Swain M.G., et al. Rituximab for primary biliary cirrhosis (PBC) refractory to ursodeoxycholic acid (UDCA). Hepatology 46 Suppl 1 (2007) 550A