Primary Biliary Cirrhosis: Clinical Aspects

  • Marshall M. Kaplan


Primary biliary cirrhosis, a chronic, progressive, and often fatal cholestatic liver disease, is characterized by the destruction of intrahepatic bile ducts, portal inflammation and scarring, and the eventual development of cirrhosis and liver failure. The diagnosis is usually made in a middle-aged woman (although the age range is 20–80 years) who initially has fatigue or itching or who is asymptomatic and has been found to have unexplained hepatomegaly or an elevated serum alkaline phosphatase level. Biochemical tests of liver function typically reveal a cholestatic pattern; i. e., the alkaline phosphatase and γ-glutamyltranspeptidase are disproportionately elevated compared with other biochemical tests. A positive antimitochondrial antibody test, present in 95% of patients with primary biliary cirrhosis, makes the diagnosis very likely. It is still important to ascertain that the bile ducts are patent. This can usually be done with ultrasonography or computed tomography (CT) scanning. If the results of these tests are equivocal, endoscopic retrograde cholangiopancreatography should be done. Percutaneous needle biopsy of the liver will provide confirmatory information and permit histologic staging of the disease. This is helpful in assessing prognosis.


Primary Biliary Cirrhosis Renal Tubular Acidosis Wilson Disease Primary Biliary Cirrhosis Patient Prospective Control Trial 
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  1. 1.
    Hamlyn AN, Sherlock S: The epidemiology of primary biliary cirrhosis: A survey of mortality in England and Wales. Gut 15:473–479, 1974.PubMedCrossRefGoogle Scholar
  2. 2.
    Hamlyn AN, Macklan AF, James O: Primary biliary cirrhosis: Geographical clustering and symptomatic onset seasonality. Gut 29:970–975, 1983.Google Scholar
  3. 3.
    Triger DR, Berg PA, Rodes J: Epidemiology of primary biliary cirrhosis. Liver 4:195–200, 1984.PubMedGoogle Scholar
  4. 4.
    Lofgren J, Jarnerot G, Danielson D, Herndal I: Incidence and prevalence of primary biliary cirrhosis in a defined population of Sweden. Scand J Gastroenterol 20:647–650, 1985.PubMedCrossRefGoogle Scholar
  5. 5.
    Dickson ER, Fleming CR, Ludwig J: Primary biliary cirrhosis, in Popper H, Schaffner F (eds): Progress in Liver Diseases. Vol. 6. Grune & Stratton, Orlando, Florida, 1978, pp. 487–502.Google Scholar
  6. 6.
    Galbraith RM, Smith M, MacKenzie RM, et al: High prevalence of serioimmunologic abnormalities in relatives of patients with active chronic hepatitis or primary biliary cirrhosis. S Engl J Med 290:63–69, 1974.CrossRefGoogle Scholar
  7. 7.
    Miller KB, Sepersky RA, Brown KM, et al: Genetic abnormalities of immunoregulation in primary biliary cirrhosis. Am J Med 65:75–80, 1983.CrossRefGoogle Scholar
  8. 8.
    Gores GJ, Moore SB, Fisher LD, et al: Primary biliary cirrhosis: Associations with major histocompatibility complex class II antigens. Gastroenterology 90:1728, 1986 (abst).Google Scholar
  9. 9.
    Bassendine MF, Dewar PJ, James DFW: HLA-DR antigens in primary biliary cirrhosis: Lack of association. Gut 26:625–628, 1985.PubMedCrossRefGoogle Scholar
  10. 10.
    Johnston DE, Kaplan MM, Miller KB, et al: Histocompatibility antigens in primary biliary cirrhosis, Am J Gastroenterol 82:1127–1129, 1987.PubMedGoogle Scholar
  11. 11.
    James SP, Hoofhagle JH, Strober W, Jones EA: Primary biliary cirrhosis: A model autoimmune disease. Ann Intern Med 99:500–512, 1983.PubMedGoogle Scholar
  12. 12.
    Epstein O: The pathogenesis of primary biliary cirrhosis. Mol Aspects Med 3:293–305, 1985.CrossRefGoogle Scholar
  13. 13.
    MacSween RN, Burt AD: The cellular pathology of primary biliary cirrhosis. Mol Aspects Med 3:269–291, 1985.CrossRefGoogle Scholar
  14. 14.
    McFarlane IG: Autoreactivity against biliary tract antigens in primary biliary cirrhosis. Mol Aspects Med 3:249–267, 1985.CrossRefGoogle Scholar
  15. 15.
    Culp KS, Fleming CR, Duffy J, et al: Autoimmune associations in primary biliary cirrhosis. Mayo Clin Proc 57:365–370, 1982.PubMedGoogle Scholar
  16. 16.
    Lindgren S, Eriksson S: IgM in primary biliary cirrhosis. Physicochemical and complement activating properties. J Lab Clin Med 99:636–645, 1982.PubMedGoogle Scholar
  17. 17.
    Taal BG, Schalm SW: Cryoglobulins in primary biliary cirrhosis: prevalence and modulation by immunosuppressive therapy. S Gastroenterol 23:228–234, 1985.Google Scholar
  18. 18.
    Lindgren S, Johnson U: Complement activation in primary biliary cirrhosis: An in vitro model. J Lab Clin Med 105:432–435, 1985.PubMedGoogle Scholar
  19. 19.
    Fakunle YM, Aranguibel F, DeVilliers D, et al: Monomeric IgM in chronic liver disease. Clin Exp Immunol 38:204–210, 1979.PubMedGoogle Scholar
  20. 20.
    Nouria-Aria KT, Hegarty JE, Neuberger J, et al: In vitro studies on the mechanism of increased serum IgM levels in primary biliary cirrhosis. Clin Exp Immunol 61:297–304, 1985.Google Scholar
  21. 21.
    James SP, Jones EA, Hoffnagle JH, Strober W: Circulating activated S cells in primary biliary cirrhosis. J Clin Immunol 5:254–260, 1985.PubMedCrossRefGoogle Scholar
  22. 22.
    Ruffati A, Arslan P, Floreani A, et al: Nuclear membrane-staining antinuclear antibody in patients with primary biliary cirrhosis. J Clin Immunol 5:357–361, 1985.CrossRefGoogle Scholar
  23. 23.
    Elta GH, Sepersky RA, Connors CM, et al: Increased incidence of hypothyroidism in primary biliary cirrhosis. Dig Dis Sci 28:971–975, 1983.PubMedCrossRefGoogle Scholar
  24. 24.
    Pares A, Martorell J, Caballeria J, et al: Lymphocytotoxic antibodies in primary biliary cirrhosis. Dig Dis Sci 30:829–833, 1985.PubMedCrossRefGoogle Scholar
  25. 25.
    Sundewall AC, LefVert AK, Olsson R: Anti-acetylcholine receptor antibodies in primary biliary cirrhosis. Acta Med Scand 217:519–525, 1985.PubMedCrossRefGoogle Scholar
  26. 26.
    Bassendine MF, Collins JD, Stephenson J, et al: Platelet associated immunoglobulins in primary biliary cirrhosis: A cause of thrombocytopeniaS Gut 26:1074–1079, 1985.PubMedCrossRefGoogle Scholar
  27. 27.
    Penner E: Demonstration of immune complexes containing the ribonucleoprotein antigen Ro in primary biliary cirrhosis. Gastroenterology 90:724–727, 1986.PubMedGoogle Scholar
  28. 28.
    Baum H, Berg PA: The complex nature of mitochondrial antibodies and their relation to primary biliary cirrhosis. Semin Liver Dis 4:309–321, 1981.CrossRefGoogle Scholar
  29. 29.
    Lindenborn-Fotinos J, Baum H, Berg PA: Mitochondrial antibodies in primary biliary cirrhosis: Species and nonspecies specific determinants of M2 antigen. Hepatology 5:763–769, 1985.PubMedCrossRefGoogle Scholar
  30. 30.
    Mendel-Hartvig I, Nelson BD, Loof L, Totterman TH: Primary biliary cirrhosis: Further biochemical and immunological characterization of mitochondrial antigens. Clin Exp Immunol 62:371–379, 1985.PubMedGoogle Scholar
  31. 31.
    Frazer IH, MacKay IR, Jordan TW, et al: Reactivity of anti-mitochondrial autoantibodies in primary biliary cirrhosis: Definition of two novel mitochondrial polypeptide autoantigens. J Immunol 135:1739–1745, 1985.PubMedGoogle Scholar
  32. 32.
    Weber P, Brenner J, Strechemesser E, et al: Characterization and clinical relevance of a new complement-fixing antibody-anti-M8 in patients with primary biliary cirrhosis. Hepatology 6:553–559, 1986.PubMedCrossRefGoogle Scholar
  33. 33.
    Manns M, Meyer Zum Buschenfelde K-S: A mitochondrial antigen-antibody system in cholestatic liver disease detected by radioimmunoassay. Hepatology 5:763–769, 1985.CrossRefGoogle Scholar
  34. 34.
    Kaplan MM, Gandolfo JV, Quaroni EG: An enzyme-linked immunoabsorbent assay (ELISA) for detecting antimitochondrial antibody. Hepatology 4:727–730, 1984.PubMedCrossRefGoogle Scholar
  35. 35.
    Jones EA, Frank MM, Jaffe CJ, Vierling JM: Primary biliary cirrhosis and the complement system. Ann Intern Med 90:72–84, 1979.Google Scholar
  36. 36.
    Lindgren S, Laurell S-B, Eriksson S: Complement components and activation in primary biliary cirrhosis. Hepatology 4:9–14, 1984.PubMedCrossRefGoogle Scholar
  37. 37.
    Al-Agbar MN, Neuberger J, Williams R, Eddieston AL: Mononuclear cell complement receptor blockade in primary biliary cirrhosis. Gut 26:20–25, 1985.CrossRefGoogle Scholar
  38. 38.
    Minuk GY, Vergalla J, Hanson RG, et al: Anticomplement receptor activity in the serum of patients with primary biliary cirrhosis. Gut 27:324–328, 1986.PubMedCrossRefGoogle Scholar
  39. 39.
    Wands JR, Dienstag JL, Bhan AK, et al: Circulating immune complexes and complement activation in primary biliary cirrhosis. S Engl J Med 298:223–237, 1978.Google Scholar
  40. 40.
    Gupta RC, Dickson ER, McDuffie FC, Baggenstoss AH: Circulating IgG complexes in primary biliary cirrhosis: A serial study in forty patients followed for two years. Clin Exp Immunol 34:19–27, 1978.PubMedGoogle Scholar
  41. 41.
    Amoroso P, Vergani D, Wojicika BM, et al: Identification of biliary antigens in circulating immune complexes in primary biliary cirrhosis. Clin Exp Immunol 42:95–98, 1980.PubMedGoogle Scholar
  42. 42.
    Penner EH, Goldenberg H, Albini B, et al: Immune complexes in primary biliary cirrhosis contain mitochondrial antigens. Clin Immun Immunopathol 22:394–399, 1982.CrossRefGoogle Scholar
  43. 43.
    Goldberg MJ, Kaplan MM, Mitamura T, et al: Evidence against an immune complex pathogenesis of primary biliary cirrhosis. Gastroenterology 83:677–683, 1982.PubMedGoogle Scholar
  44. 44.
    Bahn AK, Dienstag JL, Wands JR, et al: Alterations of T-cell subsets in primary biliary cirrhosis. Clin Exp Immunol 47:351–358, 1982.Google Scholar
  45. 45.
    Miller KB, Elta GH, Rudders RA, Kaplan MM: Lymphocyte subsets in primary biliary cirrhosis. Ann Intern Med 100:385–387, 1984.PubMedGoogle Scholar
  46. 46.
    James SP, Elson CO, Jones EA, Strober W: Abnormal regulation of immunoglobulin synthesis in vitro in primary biliary cirrhosis. Gastroenterology 79:242–244, 1980.PubMedGoogle Scholar
  47. 47.
    Zetterman RK, Woltjen JA: Supressor cell activity in primary biliary cirrhosis. Dig Dis Sci 25:104–107, 1980.PubMedCrossRefGoogle Scholar
  48. 48.
    James SP, Elson CO, Waggoner JG, et al: Deficiency of the autologous mixed lymphocyte reaction in patients with primary biliary cirrhosis. J Clin Invest 66:1305–1310, 1980.PubMedCrossRefGoogle Scholar
  49. 49.
    Ballardini G, Mirakian R, Bianchi FB, et al: Aberrant expression of HLA-DR antigens on bile duct epithelium in primary biliary cirrhosis: Relevance to pathogenesis. Lancet 2:1009–1013, 1984.PubMedCrossRefGoogle Scholar
  50. 50.
    Zinkernagel RM, Doherty PC: MCH-restricted cytotoxic cells: Studies on the biological role of polymorphic major transplantation antigens determine S cell restriction-specificity, functions, and responsiveness. Adv Immunol 27:51–177, 1979.PubMedCrossRefGoogle Scholar
  51. 51.
    Bernau D, Feldmann G, Degott MD, Gisselbrecht C: Ultrastructural lesions and bile ducts in primary biliary cirrhosis. A comparison with the lesions observed in graft versus host disease. Hum Pathol 12:782–793, 1981.CrossRefGoogle Scholar
  52. 52.
    Neuberger J, Portmann B, MacDougall BRD, et al: Recurrence of primary biliary cirrhosis after liver transplantation. S Engl J Med 306:1–4, 1982.CrossRefGoogle Scholar
  53. 53.
    McFarlane IG, Wojcicka BM, Isantoulas DC, et al: Leukocyte migration inhibition in response to biliary antigens in primary biliary cirrhosis, sclerosing cholangitis, and other liver diseases. Gastroenterology 76:1333–1340, 1979.PubMedGoogle Scholar
  54. 54.
    James SP, Jones EA: Abnormal natural killer cytotoxicity in primary biliary cirrhosis: Evidence for a functional deficiency of cytolytic effector cells. Gastroenterology 89:165–171, 1985.PubMedGoogle Scholar
  55. 55.
    Vierling JM, Nelson DL, Strober W, et al: In vitro cell-mediated cytotoxicity in primary biliary cirrhosis and chronic hepatitis: Dysfunction of spontaneous cell-mediated cytotoxicity in primary biliary cirrhosis. J Clin Invest 60:1116–1128, 1977.PubMedCrossRefGoogle Scholar
  56. 56.
    Geubel AP, Keller RH, Summerskill WHJ, et al: Lymphocyte cytotoxicity and inhibition studied with autologous liver cells: Observations in chronic active liver disease and the primary biliary cirrhosis syndrome. Gastroenterology 71:450–456, 1976.PubMedGoogle Scholar
  57. 57.
    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 78:236–246, 1980.PubMedGoogle Scholar
  58. 58.
    Shapiro JM, Smith H, Schaffner F: Serum bilirubin, a prognostic factor in primary biliary cirrhosis. Gut 20:137–140, 1979.PubMedCrossRefGoogle Scholar
  59. 59.
    Sasaki H, Inoue K, Higuchi K, et al: Primary biliary cirrhosis in Japan: National survey by the subcommittee on autoimmune hepatitis. Gastroenterology Jpn 5:476–485, 1985.Google Scholar
  60. 60.
    Jahn CE, Schaeffer EJ, Taam LA, et al: Lipoprotein abnormalities in primary biliary cirrhosis. Gastroenterology 89:1266–1278, 1985.PubMedGoogle Scholar
  61. 61.
    Teramoto T, Kato H, Hashimoto Y, et al: Abnormal high density lipoprotein of primary biliary cirrhosis analyzed by high performance chromatography. Clin Chim Acta 149:135–148, 1985.PubMedCrossRefGoogle Scholar
  62. 62.
    Sherlock S, Scheuer PJ: The presentation and diagnosis of 100 patients with primary biliary cirrhosis. S Engl J Med 289:674–678, 1973.CrossRefGoogle Scholar
  63. 63.
    Ghent CN, Bloomer JR, Klatskin G: Elevations in skin tissue levels of bile acids in human cholestasis: Relation to serum levels and to pruritus. Gastroenterology 73:1125–1130, 1977.PubMedGoogle Scholar
  64. 64.
    Haensch HP, Balzer K, Kylewizc 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 28:475–477, 1985.CrossRefGoogle Scholar
  65. 65.
    Ambinder EP, Cohen LB, Wolke AM, et al: The clinical effectiveness and safety of chronic plasmapheresis in patients with primary biliary cirrhosis. J Clin Apheresis 2:219–223, 1985.PubMedCrossRefGoogle Scholar
  66. 66.
    Roll J, Boyer JL, Barry D, Klatskin G: The prognostic importance of clinical and histologic features in asymptomatic and symptomatic primary biliary cirrhosis. S Engl J Med 308:1–7, 1983.CrossRefGoogle Scholar
  67. 67.
    James O, Macklin AF, Watson AJ: Primary biliary cirrhosis—A revised clinical spectrum. Lancet 1:1278–1281, 1981.PubMedGoogle Scholar
  68. 68.
    Dickson ER, Fleming TR, Wiesner RH, et al: Trial of penicillamine in advanced primary biliary cirrhosis. S Engl J Med 312:1011–1015, 1985.CrossRefGoogle Scholar
  69. 69.
    Long RG, Scheuer PJ, Sherlock S: Presentation and course of asymptomatic primary biliary cirrhosis. Gastroenterology 72:1204–1207, 1977.PubMedGoogle Scholar
  70. 70.
    Ros E, Garcia-Puges A, Reixach M, et al: Fat digestion and exocrine pancreatic function in primary biliary cirrhosis. Gastroenterology 87:180–187, 1984.PubMedGoogle Scholar
  71. 71.
    Lanspa SJ, Chan AT, Bell JS III, et al: Pathogenesis of steatorrhea in primary biliary cirrhosis. Hepatology 5:837–842, 1985.PubMedCrossRefGoogle Scholar
  72. 72.
    Herlong HF, Recker RR, Maddrey WC: Bone disease in primary biliary cirrhosis: Histologic features and response to 25-hydroxyvitamin D. Gastroenterology 83:103–108, 1982.PubMedGoogle Scholar
  73. 73.
    Matloff DS, Kaplan MM, Neer RM, et al: Osteoporosis in primary biliary cirrhosis: Effects of 25-hydroxyvitamin D3 treatment. Gastroenterology 83:97–102, 1982.PubMedGoogle Scholar
  74. 74.
    Epstein O, Chapman RWG, Lake-Bakaar G, et al: The pancreas in primary biliary cirrhosis and primary sclerosing cholangitis. GSstroenterology 83:1177–1182, 1982.Google Scholar
  75. 75.
    Kehayoglou AK, Holdsworth CD, Agnew JE, et al: Bone disease and calcium absorption in primary biliary cirrhosis—With special reference to vitamin D therapy. Lancet 1:715–719, 1968.PubMedCrossRefGoogle Scholar
  76. 76.
    Reed JS, Meredith SC, Nemchausky BA, et al: Bone disease in primary biliary cirrhosis: Reversal of osteomalacia with oral 25-hydroxyvitamin D. Gastroenterology 78:512–517, 1980.PubMedGoogle Scholar
  77. 77.
    Long RG: Hepatic osteodystrophy: Outlook good but some problems unsolved. Gastroenterology 78:644–647, 1980.PubMedGoogle Scholar
  78. 78.
    Kaplan MM, Goldberg MJ, Matloff DS, et al: Effect of 25-hydroxyvitamin D3 metabolites in primary biliary cirrhosis. Gastroenterology 81:681–685, 1981.PubMedGoogle Scholar
  79. 79.
    Krawitt EL, Grundman MJ, Mawer EB: Absorption, hydroxylation, and excretion of vitamin D3 in primary biliary cirrhosis. Lancet 2:1246–1249, 1977.PubMedCrossRefGoogle Scholar
  80. 80.
    Mawer EB, Klass HJ, Warnes TW, Berry JL: Metabolism of vitamin D in patients with primary biliary cirrhosis and alcoholic liver disease. Clin Sci 69:561–570, 1985.PubMedGoogle Scholar
  81. 81.
    Jung RT, Davie M, Siklos M, et al: Vitamin D metabolism in acute and chronic cholestasis. Gut 20:840–847, 1979.PubMedCrossRefGoogle Scholar
  82. 82.
    Hodgson SF, Dickson ER, Wahner HW, et al: Bone loss and reduced osteoblastic function in primary biliary cirrhosis. Ann Intern Med 103:855–860, 1985.PubMedGoogle Scholar
  83. 83.
    Cuthbert JA, Pak CYC, Zerwekh JE, et al: Bone disease in primary biliary cirrhosis: Increased bone resorption and turnover in the absence of osteoporosis or osteomalacia. Hepatology 1:1–8, 1981.CrossRefGoogle Scholar
  84. 84.
    Herlong HF, Russell RM, Maddrey WC: Vitamin A and zinc therapy in primary biliary cirrhosis. Hepatology 1:348–381, 1981.PubMedCrossRefGoogle Scholar
  85. 85.
    Shepherd AN, Bedford GJ, Hill A, Bouchier IA: Primary biliary cirrhosis. Dark adaptometry, electrooculography and vitamin A state. Br Med J 289:1484–1485, 1984.CrossRefGoogle Scholar
  86. 86.
    Elta GH, Furie BC, Furie B, et al: Fat soluble vitamins in primary biliary cirrhosis. Hepatology 2:703 1982 (abst).Google Scholar
  87. 87.
    Spinsi R, Smith-Laing G, Epstein O, Sherlock S: Results of portal decompression in patients with primary biliary cirrhosis. Gut 22:345–349, 1981.PubMedCrossRefGoogle Scholar
  88. 88.
    Sepersky R, Callow A, Kanel G, Kaplan MM: Portasystemic shunts in primary biliary cirrhosis: Survival is the same as in patients with Laennec’s cirrhosis and postnecrotic cirrhosis. Dig Dis Sci 27:507–512, 1982.PubMedCrossRefGoogle Scholar
  89. 89.
    Alarcon-Segovia D, Diaz-Jouanen E, Fishbein E: Features of Sjögren’s syndrome in primary biliary cirrhosis. Ann Intern Med 79:31–36, 1973.PubMedGoogle Scholar
  90. 90.
    Giovannini A, Ballardini G, Bonazzoli P, Bianchi FB: Patterns of lacrimal dysfunction in primary biliary cirrhosis. Br J Ophthalmol 69:832–835, 1985.PubMedCrossRefGoogle Scholar
  91. 91.
    Clark AK, Galbraith RM, Hamilton EBD, et al: Rheumatic disorders in primary biliary cirrhosis. Ann Rheum Dis 37:42–47, 1978.CrossRefGoogle Scholar
  92. 92.
    Crowe JP, Malloy MG, Wells I, et al: Increased Clq binding and arthritis in primary biliary cirrhosis. Gut 21:418–422, 1980.PubMedCrossRefGoogle Scholar
  93. 93.
    Crowe JP, Christensen E, Butler J, et al: Primary biliary cirrhosis and the prevalence of hypothyroidism and its relationship to thyroid autoantibodies and sicca syndrome. Gastroenterology 78:1437–1441, 1980.PubMedGoogle Scholar
  94. 94.
    Pares A, Rimola A, Bruguera M, et al: Renal tubular acidosis in primary biliary cirrhosis. Gastroenterology 80:681–686, 1981.PubMedGoogle Scholar
  95. 95.
    Melia WM, Johnson PJ, Neuberger J, et al: Hepatocellular carcinoma in primary biliary cirrhosis: Detection by alpha-fetoprotein estimation. Gastroenterology 87:660–663, 1984.PubMedGoogle Scholar
  96. 96.
    Wolke AM, Schaffher F, Kopelman B, Sacks HS: Malignancy in primary biliary cirrhosis. High incidence of breast cancer in affected women. Am J Med 76:1075–1078, 1984.PubMedCrossRefGoogle Scholar
  97. 97.
    Goudie BM, Burt AD, Boyle P, et al: Breast cancer in women with primary biliary cirrhosis. Br Med J 291:1597–1598, 1985.CrossRefGoogle Scholar
  98. 98.
    Burroughs AK, Rosenstein IJ, Epstein O, et al: Bacteriuria and primary biliary cirrhosis. Gut 25:133–137, 1984.PubMedCrossRefGoogle Scholar
  99. 99.
    Christensen E, Neuberger J, Crowe J, et al: Beneficial effect of azathioprine and prediction of prognosis in primary biliary cirrhosis. Gastroenterology 89:1084–1091, 1985.PubMedGoogle Scholar
  100. 100.
    James OFW: D-Penicillamine for primary biliary cirrhosis. Gut 26:109–113, 1985.PubMedCrossRefGoogle Scholar
  101. 101.
    Neuberger J, Christensen E, Portmann B, et al: Double blind controlled trial of D-penicillamine in patients with primary biliary cirrhosis. Gut 26:114–119, 1985.PubMedCrossRefGoogle Scholar
  102. 102.
    Beswick DR, Klatskin G, Boyer JL: Asymptomatic primary biliary cirrhosis. Gastroenterology 89:267–271, 1985.PubMedGoogle Scholar
  103. 103.
    Lee RG, Epstein O, Jauregi H, et al: Granulomas in primary biliary cirrhosis: A prognostic feature. Gastroenterology 81:983–986, 1981.PubMedGoogle Scholar
  104. 104.
    Portmann B, Popper H, Neuberger J, Williams R: Sequential and diagnostic features in primary biliary cirrhosis based on serial histologic study in 209 patients. Gastroenterology 88:1777–1790, 1985.PubMedGoogle Scholar
  105. 105.
    Heathcote J, Ross A, Sherlock S: A prospective controlled trial of azathioprine in primary biliary cirrhosis. Gastroenterology 70:656–660, 1976.PubMedGoogle Scholar
  106. 106.
    Crowe J, Christensen E, Smith M, et al: Azathioprine in primary biliary cirrhosis: A preliminary report of an international trial. Gastroenterology 78:1005–1010, 1980.PubMedGoogle Scholar
  107. 107.
    Epstein O, Jain S, Lee RG, et al: D-Penicillamine treatment improves survival in primary biliary cirrhosis. Lancet 1:1275–1277, 1981.PubMedCrossRefGoogle Scholar
  108. 108.
    Matloff DS, Alpert E, Resnick RH, Kaplan MM: A prospective trial of D-penicillamine in primary biliary cirrhosis. S Engl J Med 306:319–326, 1982.CrossRefGoogle Scholar
  109. 109.
    Epstein O, Cook DG, Jain S, et al: D-Penicillamine and clinical trials in primary biliary cirrhosis. Hepatology 4:1032, 1984 (abst).Google Scholar
  110. 110.
    Bodenheimer HC Jr, Schaffner F, Sternlieb I, et al: A prospective clinical trial of D-penicillamine in the treatment of primary biliary cirrhosis. Hepatology 5:1139–1142, 1985.PubMedCrossRefGoogle Scholar
  111. 111.
    Epstein O, Arborgh B, Sagiv M, et al: Is copper hepatotoxic in primary biliary cirrhosisS J Clin Pathol 34:1071–1075, 1981.PubMedCrossRefGoogle Scholar
  112. 112.
    Savolainen S-R, Miettinen TA, Pikkarainen P, et al: Enzymes of collagen synthesis and type III procollagen aminopropeptide in the evaluation of D-penicillamine and medroxyprogesterone treatments of primary biliary cirrhosis. Gut 24:136–142, 1983.PubMedCrossRefGoogle Scholar
  113. 113.
    Koldinger RE: Treatment of primary biliary cirrhosis with colchicine. Gastroenterology 78:1309, 1980 (abst).Google Scholar
  114. 114.
    Kaplan MM, Ailing DW, Zimmerman HJ, et al: A prospective trial of colchicine for primary biliary cirrhosis. S Engl J Med 315:1448–1454, 1986.CrossRefGoogle Scholar
  115. 115.
    Warnes TW, Smith A, Lee F, et al: A controlled trial of colchicine in primary biliary cirrhosis. Hepatology 4:1022, 1984 (abst).Google Scholar
  116. 116.
    Bodenheimer H Jr, Schaffner F, Pezzullo J: Colchicine therapy in primary biliary cirrhosis. Hepatology 6:1172, 1986.Google Scholar
  117. 117.
    Hoofnagle JH, David GL, Schafer DF, et al: Randomized trial of chlorambucil for primary biliary cirrhosis. Gastroenterology 91:1327–1334, 1986.PubMedGoogle Scholar
  118. 118.
    Routhier G, Epstein O, Janossy G, et al: The effects of cyclosporin A on suppresion and inducer T-lymphocytes in primary biliary cirrhosis. Lancet 3:1223–1226, 1980.CrossRefGoogle Scholar
  119. 119.
    Scharschmidt BF: Human liver transplantation: Analysis of data on 540 patients from four centers. Hepatology 4:955–1015, 1984.CrossRefGoogle Scholar
  120. 120.
    Van Thiel DH, Tarter R, Gavaler JS, et al: Liver transplantation in adults. An analysis of costs and benefits at the University of Pittsburgh. Gastroenterology 90:211–216, 1986.PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1989

Authors and Affiliations

  • Marshall M. Kaplan
    • 1
    • 2
  1. 1.Division of GastroenterologyTufts University School of MedicineNew EnglandUSA
  2. 2.Medical Center HospitalsBostonUSA

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