Skip to main content
SpringerLink
Log in

Drug Therapy in the Management of Type 1 Autoimmune Hepatitis

  • Review Article
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Prednisone alone or in combination with azathioprine is the treatment of choice for severe type 1 autoimmune hepatitis. The combination regimen is preferred, especially in the elderly, because of a lower incidence of corticosteroid-related complications. Only patients with sustained severe laboratory abnormalities, bridging necrosis or multilobular necrosis on histological assessment, and/or incapacitating symptoms, have absolute indications for treatment based on controlled clinical trials. The institution of therapy must be individualised in other patients, based mainly on symptoms and disease behaviour.

Serum aspartate aminotransferase and γ-globulin levels are the most useful indices to monitor during therapy. Liver tissue examination is the best method of evaluating completeness of response. Most patients enter remission, but relapse occurs in 50 to 86% after drug withdrawal. Maintenance therapy with low dosages of prednisone or azathioprine can be used long term in patients who have relapsed repeatedly.

Inability to achieve remission after 3 years (incomplete response), deterioration during therapy (treatment failure) and drug toxicity are unsatisfactory responses that warrant alternative strategies. Liver transplantation is effective in managing decompensated disease, but recurrence of autoimmune hepatitis after transplantation is possible. Tacrolimus and budesonide are promising new drugs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Czaja AJ. Autoimmune hepatitis: evolving concepts and treatment strategies. Dig Dis Sci 1995 Feb; 40: 435–56

    PubMed  CAS  Google Scholar 

  2. Nikias GA, Batts KP, Czaja AJ. The nature and prognostic implications of autoimmune hepatitis with an acute presentation. J Hepatol 1994; 21: 866–71

    PubMed  CAS  Google Scholar 

  3. Johnson PJ, McFarlane IG, Alvarez F, et al. Meeting report: International Autoimmune Hepatitis Group. Hepatology 1993 Oct; 18: 998–1005

    PubMed  CAS  Google Scholar 

  4. Czaja AJ, Carpenter HA. Validation of a scoring system for the diagnosis of autoimmune hepatitis. Dig Dis Sci 1996 Feb; 41: 305–14

    PubMed  CAS  Google Scholar 

  5. Czaja AJ, Manns MP. The validity and importance of subtypes of autoimmune hepatitis: a point of view. Am J Gastroenterol 1995 Aug; 90: 1206–11

    PubMed  CAS  Google Scholar 

  6. Homberg J-C, Abuaf N, Bernard O, et al. Chronic active hepatitis associated with antiliver/kidney microsome antibody type 1: a second type of ‘autoimmune’ hepatitis. Hepatology 1987 Jun; 7: 1333–9

    PubMed  CAS  Google Scholar 

  7. Czaja AJ, Manns MP, Homburger HA. Frequency and significance of antibodies to liver/kidney microsome type 1 in adults with chronic active hepatitis. Gastroenterology 1992 Oct; 103: 1290–5

    PubMed  CAS  Google Scholar 

  8. Manns MP, Griffin KJ, Sullivan KF, et al. LKM-1 autoantibodies recognize a short linear sequence in P450IID6, a cytochrome P-450 monooxygenase. J Clin Invest 1991 Oct; 88: 1370–8

    PubMed  CAS  Google Scholar 

  9. Manns M, Gerken G, Kyriatsoulis A, et al. Characterization of a new subgroup of autoimmune chronic active hepatitis by autoantibodies against a soluble liver antigen. Lancet 1987 Feb; I: 292–4

    Google Scholar 

  10. Stechemesser E, Klein R, Berg PA. Characterization and clinical relevance of liver-pancreas antibodies in autoimmune hepatitis. Hepatology 1993 Jul; 18: 1–9

    PubMed  CAS  Google Scholar 

  11. Czaja AJ, Carpenter HA, Manns MP. Antibodies to soluble liver antigen, P450IID6, and mitochondrial complexes in chronic hepatitis. Gastroenterology 1993 Nov; 105: 1522–8

    PubMed  CAS  Google Scholar 

  12. Cook GC, Mulligan R, Sherlock S. Controlled prospective trial of corticosteroid therapy in active chronic hepatitis. Q J Med 1971 Apr; 40: 159–85

    PubMed  CAS  Google Scholar 

  13. Soloway RD, Summerskill WHJ, Baggenstoss AH, et al. Clinical, biochemical, and histological remission of severe chronic active liver disease: a controlled study of treatments and early prognosis. Gastroenterology 1972 Nov; 63: 820–33

    PubMed  CAS  Google Scholar 

  14. Murray-Lyon IM, Stern RB, Williams R. Controlled trial of prednisone and azathioprine in active chronic hepatitis. Lancet 1973 Apr; I: 735–7

    Google Scholar 

  15. Maggiore G, Bernard O, Homberg J-C, et al. Liver disease associated with anti-liver-kidney microsome antibody in children. J Pediatr 1986; 108: 399–404

    PubMed  CAS  Google Scholar 

  16. Czaja AJ. Autoantibodies. Baillieres Clin Gastroenterol 1995 Dec; 9: 723–44

    PubMed  CAS  Google Scholar 

  17. Cochrane AMG, Moussouros A, Thomson AD, et al. Antibody-dependent cell-mediated (K cell) cytotoxicity against isolated hepatocytes in chronic active hepatitis. Lancet 1976; I: 441–4

    Google Scholar 

  18. Vento S, Nouri-Aria KT, Eddieston ALWF. Immune mechanisms in autoimmune chronic active hepatitis. Scand J Gastroenterol 1985; 20 Suppl. 114: 91–103

    Google Scholar 

  19. McFarlane IG, McFarlane BM, Major GN, et al. Identification of the hepatic asialo-glycoprotein receptor (hepatic lectin) as a component of liver specific membrane lipoprotein (LSP). Clin Exp Immunol 1984; 55: 347–54

    PubMed  CAS  Google Scholar 

  20. Poralla T, Treichel U, Lohr H, et al. The asialoglycoprotein receptor as target structure in autoimmune liver diseases. Semin Liver Dis 1991; 11: 215–22

    PubMed  CAS  Google Scholar 

  21. Loeper J, Descatoire V, Maurice M, et al. Cytochromes P-450 in human hepatocyte plasma membrane: recognition by several autoantibodies. Gastroenterology 1993; 104: 203–16

    PubMed  CAS  Google Scholar 

  22. Czaja AJ. Autoimmune hepatitis and viral infection. Gastroenterol Clin North Am 1994 Sep; 23: 547–66

    PubMed  CAS  Google Scholar 

  23. Vento S, Garofano T, Di Perri G, et al. Identification of hepatitis A virus as a trigger for autoimmune chronic hepatitis type 1 in susceptible individuals. Lancet 1991; 337: 1183–7

    PubMed  CAS  Google Scholar 

  24. Huppertz H-K, Treichel U, Gassel AM, et al. Autoimmune hepatitis following hepatitis A virus infection. J Hepatol 1995; 23: 204–8

    PubMed  CAS  Google Scholar 

  25. Laskus T, Slusarczyk J. Autoimmune chronic active hepatitis developing after acute type B hepatitis. Dig Dis Sci 1989; 34: 1294–7

    PubMed  CAS  Google Scholar 

  26. Magrin S, Craxi A, Fiorentino G, et al. Is autoimmune chronic active hepatitis a HCV-related disease? J Hepatol 1991; 13: 56–60

    PubMed  CAS  Google Scholar 

  27. Magrin S, Craxi A, Fabiano C, et al. Hepatitis C virus replication in ‘autoimmune’ chronic hepatitis. J Hepatol 1991; 13: 364–7

    PubMed  CAS  Google Scholar 

  28. Ramadori G, Lohr H, Rossol S, et al. Human immunodeficiency virus infection mimics autoimmune hepatitis — a case report. Klin Wochenschr 1988; 66: 1040

    PubMed  CAS  Google Scholar 

  29. Robertson DAF, Zhang SL, Guy EC, et al. Persistent measles virus genome in autoimmune chronic active hepatitis. Lancet 1987; II: 9–11

    Google Scholar 

  30. Kalland K-H, Endresen C, Haukenes G, et al. Measles-specific nucleotide sequences and autoimmune chronic active hepatitis. Lancet 1989; I: 1390–1

    Google Scholar 

  31. Czaja AJ. Overlap of chronic viral hepatitis and autoimmune hepatitis. In: Willson RA, editor. Viral hepatitis: diagnosis, treatment, prevention. New York: Marcel Dekker, 1997: 371–99

    Google Scholar 

  32. Reynolds TB, Peters RL, Yamada S. Chronic active and lupoid hepatitis caused by a laxative, oxyphenisatin. N Engl J Med 1971; 285: 813–20

    PubMed  CAS  Google Scholar 

  33. Maddrey WC, Boitnott JK. Severe hepatitis from methyldopa. Gastroenterology 1975; 68: 351–60

    PubMed  CAS  Google Scholar 

  34. Rodman JS, Deutsch DJ, Gutman SI. Methyldopa hepatitis: a report of six cases and review of the literature. Am J Med 1976; 60: 941–8

    PubMed  CAS  Google Scholar 

  35. Sharp JR, Ishak KG, Zimmerman HJ. Chronic active hepatitis and severe hepatic necrosis associated with nitrofurantoin. Ann Intern Med 1980; 92: 14–9

    PubMed  CAS  Google Scholar 

  36. Gough A, Chapman S, Wagstaff K, et al. Minocycline induced autoimmune hepatitis and systemic lupus erythematosus-like syndrome. BMJ 1996; 312: 169–72

    PubMed  CAS  Google Scholar 

  37. Crosson J, Stillman MT. Minocycline-related lupus erythema-tosus with associated liver disease. J Am Acad Dermatol 1997 May; 36: 867–8

    PubMed  CAS  Google Scholar 

  38. Herzog D, Hajoui O, Russo P, et al. Study of immune reactivity of minocycline-induced chronic active hepatitis. Dig Dis Sci 1997; 42: 1100–3

    PubMed  CAS  Google Scholar 

  39. Helfgott SM, Sandberg-Cook J, Zakim D, et al. Diclofenac-associated hepatotoxicity. JAMA 1990; 264: 2660–2

    PubMed  CAS  Google Scholar 

  40. Scully LJ, Clarke D, Barr RJ. Diclofenac induced hepatitis: 3 cases with features of autoimmune chronic active hepatitis. Dig Dis Sci 1993; 38: 744–51

    PubMed  CAS  Google Scholar 

  41. Sterling MJ, Kane M, Grace ND. Pemoline-induced autoimmune hepatitis. Am J Gastroenterol 1996; 91: 2233–4

    PubMed  CAS  Google Scholar 

  42. Fedotin MS, Lefer LG. Liver disease caused by propylthiouracil. Arch Intern Med 1975; 135: 319–21

    PubMed  CAS  Google Scholar 

  43. Ogburn RM, Myers RL, Burdick GE. Hepatitis associated with dantrolene sodium. Ann Intern Med 1976 Jan; 84: 53–4

    PubMed  CAS  Google Scholar 

  44. Utili R, Boitnott J, Zimmerman HJ. Dantrolene associated hepatic injury. Gastroenterology 1977; 72: 610–6

    PubMed  CAS  Google Scholar 

  45. Tonder M, Norday A, Elgjo K. Sulfonamide-induced chronic liver disease. Scand J Gastroenterol 1974; 9: 93–6

    PubMed  CAS  Google Scholar 

  46. Black M, Mitchell JR, Zimmerman HJ, et al. Isoniazid-associated hepatitis in 114 patients. Gastroenterology 1975 Aug; 69: 289–302

    PubMed  CAS  Google Scholar 

  47. Kamiyama T, Nouchi T, Kojima S, et al. Autoimmune hepatitis triggered by administration of an herbal medicine. Am J Gastroenterol 1997; 92: 703–4

    PubMed  CAS  Google Scholar 

  48. Maddrey WC, Boitnott JK. Drug-induced chronic liver disease. Gastroenterology 1977 Jun; 72: 1348–53

    PubMed  CAS  Google Scholar 

  49. Seeff LB. Drug-induced chronic liver disease, with emphasis on chronic active hepatitis. Semin Liver Dis 1981; 1: 104–15

    PubMed  CAS  Google Scholar 

  50. Donaldson PT, Doherty DG, Hayllar KM, et al. Susceptibility to autoimmune chronic active hepatitis: human leukocyte antigens DR4 and A1-B8-DR3 are independent risk factors. Hepatology 1991; 13: 701–6

    PubMed  CAS  Google Scholar 

  51. Czaja AJ, Carpenter HA, Santrach PJ, et al. Genetic predispositions for the immunological features of chronic active hepatitis. Hepatology 1993 Oct; 18: 816–22

    PubMed  CAS  Google Scholar 

  52. Sanchez-Urdazpal L, Czaja AJ, van Hoek B, et al. Prognostic features and role of liver transplantation in severe corticosteroid-treated autoimmune chronic active hepatitis. Hepatology 1992 Feb; 15: 215–21

    PubMed  CAS  Google Scholar 

  53. Czaja AJ, Carpenter HA, Santrach PJ, et al. Significance of HLA DR4 in type 1 autoimmune hepatitis. Gastroenterology 1993 Nov; 105: 1502–7

    PubMed  CAS  Google Scholar 

  54. Strettell MDJ, Donaldson PT, Thomson LJ, et al. Allelic basis for HLA-encoded susceptibility to type 1 autoimmune hepatitis. Gastroenterology 1997 Jun; 112: 2028–35

    PubMed  CAS  Google Scholar 

  55. Czaja AJ, Strettell MDJ, Thomson LJ, et al. Associations between alleles of the major histocompatibility complex and type 1 autoimmune hepatitis. Hepatology 1997 Feb; 25: 317–23

    PubMed  CAS  Google Scholar 

  56. Czaja AJ, Kruger M, Santrach PJ, et al. Genetic distinctions between types 1 and 2 autoimmune hepatitis. Am J Gastroenterol 1997 Dec; 92: 2197–200

    PubMed  CAS  Google Scholar 

  57. Currie MS. Immunosenescence. Comprehensive Ther 1992 Nov; 18(11): 26–34

    CAS  Google Scholar 

  58. Schwab R, Russo C, Weksler ME. Altered major histocompatibility complex-restricted antigen recognition by T cells from elderly humans. Eur J Immunol 1992; 22: 2989–93

    PubMed  CAS  Google Scholar 

  59. Talor E, Rose NR. Hypothesis: the aging paradox and autoimmune disease. Autoimmunity 1991; 8: 245–9

    PubMed  CAS  Google Scholar 

  60. Villanueva JL, Solana R, Alonso MC, et al. Changes in the expression of HLA class II antigens on peripheral blood monocytes from aged humans. Dis Markers 1990 Mar–Apr; 8(2): 85–91

    PubMed  CAS  Google Scholar 

  61. Murasko DM, Goonewardene IM. T cell function in aging: mechanisms of decline. Ann Rev Gerontol Geriatr 1990; 10: 71–96

    CAS  Google Scholar 

  62. Orson FM, Saadeh C, Lewis DE, et al. Interleukin 2 receptor expression by T cells in human aging. Cell Immunol 1989 Dec; 124(2): 278–91

    PubMed  CAS  Google Scholar 

  63. Nagel JE, Chopra RK, Powers DC, et al. Effects of age on the human high affinity interleukin 2 receptor of phytohaemag-glutinin stimulated peripheral blood lymphocytes. Clin Exp Immunol 1989 Feb; 75(2): 286–91

    PubMed  CAS  Google Scholar 

  64. Candore C, Di Lorenzo G, Caruso C, et al. The effect of age on mitogen responsive T cell precursors in human beings is completely restored by interleukin-2. Mech Ageing Dev 1992 May; 63(3): 297–307

    PubMed  CAS  Google Scholar 

  65. Paganelli R, Quinti I, Fagiolo U, et al. Changes in circulating B cells and immunoglobulin classes and subclasses in a healthy aged population. Clin Exp Immunol 1992 Nov; 90(2): 351–4

    PubMed  CAS  Google Scholar 

  66. Scully LJ, Toze C, Sengar DPS, et al. Early-onset autoimmune hepatitis is associated with a C4A gene deletion. Gastroenterology 1993 May; 104: 1478–84

    PubMed  CAS  Google Scholar 

  67. Rowley MJ, Mackay IR. Measurement of antibody-producing capacity in man: I. The normal response to flagellan from Salmonella adelaide. Clin Exp Immunol 1969; 5: 407–18

    CAS  Google Scholar 

  68. Hooper B, Whittingham S, Mathews JD, et al. Autoimmunity in a rural community. Clin Exp Immunol 1972; 12: 79–87

    PubMed  CAS  Google Scholar 

  69. Czaja AJ, Davis GL, Ludwig J, et al. Autoimmune features as determinants of prognosis in steroid-treated chronic active hepatitis of uncertain etiology. Gastroenterology 1983 Sep; 85: 713–7

    PubMed  CAS  Google Scholar 

  70. Czaja AJ. Natural history, clinical features, and treatment of autoimmune hepatitis. Semin Liver Dis 1984; 4(1): 1–12

    PubMed  CAS  Google Scholar 

  71. Mackay IR, Whittingham S, Tait B. Genetic control of immune responsiveness in man. Vox Sang 1977; 32: 10–19

    PubMed  CAS  Google Scholar 

  72. Chiovato L, Lapi P, Fiore E, et al. Thyroid autoimmunity and female gender. J Endocrinol Invest 1993; 16: 384–91

    PubMed  CAS  Google Scholar 

  73. Blomberg G, Geckeier WR, Weigert M. Genetics of the antibody response to dextran in mice. Science 1972; 177: 178–80

    PubMed  CAS  Google Scholar 

  74. Talal N, Roubinian JR. Sex hormones and autoimmunity. In: Rose NR, Bigazzi PE, Warner NL, editors. Genetic control of autoimmune disease. New York: Elsevier-North Holland, 1978: 163–74

    Google Scholar 

  75. Van Griensven M, Bergijk EC, Baelde JJ, et al. Differential effects of sex hormones on autoantibody production and proteinuria in chronic graft-versus-host disease-induced experimental lupus nephritis. Clin Exp Immunol 1997; 107: 254–60

    PubMed  Google Scholar 

  76. Czaja AJ, Carpenter HA, Santrach PJ, et al. Genetic predispositions for immunological features in chronic liver diseases other than autoimmune hepatitis. J Hepatol 1996; 24: 52–9

    PubMed  CAS  Google Scholar 

  77. Czaja AJ, Santos RM, Porto A, et al. The immune phenotype of chronic liver disease. Dig Dis Sci 1998 Sep; 43: 2149–55

    PubMed  CAS  Google Scholar 

  78. Geall MG, Schoenfield LJ, Summerskill WHJ. Classification and treatment of chronic active liver disease. Gastroenterology 1972 Dec; 63: 458–65

    Google Scholar 

  79. Schalm SW, Korman MG, Summerskill WHJ, et al. Severe chronic active liver disease: prognostic significance of initial morphologic patterns. Am J Dig Dis 1977 Nov; 22: 973–80

    PubMed  CAS  Google Scholar 

  80. DeGroote J, Fevery J, Lepoutre L. Long-term follow-up of chronic active hepatitis of moderate severity. Gut 1978; 19: 510–3

    CAS  Google Scholar 

  81. Fevery J, Desmet VJ, De Groote J. Long-term follow-up and management of asymptomatic chronic active hepatitis. In: Cohen S, Soloway RD, editors. Chronic active liver disease. New York: Churchill Livingstone, 1983: 51–64

    Google Scholar 

  82. Kemeny MJ, O’Hanlon G, Gregory PB. Asymptomatic chronic active hepatitis — prognosis and treatment [abstract]. Gastroenterology 1984; 86: 1325

    Google Scholar 

  83. Cooksley WGE, Bradbear RA, Robinson W, et al. The prognosis of chronic active hepatitis without cirrhosis in relation to bridging necrosis. Hepatology 1986; 6: 345–8

    PubMed  CAS  Google Scholar 

  84. Roberts SK, Therneau T, Czaja AJ. Prognosis of histological cirrhosis in type 1 autoimmune hepatitis. Gastroenterology 1996 Mar; 110: 848–57

    PubMed  CAS  Google Scholar 

  85. Summerskill WHJ, Korman MG, Ammon HV, et al. Prednisone for chronic active liver disease: dose titration, standard dose, and combination with azathioprine compared. Gut 1975; 16: 876–83

    PubMed  CAS  Google Scholar 

  86. Czaja AJ. Diagnosis and therapy of autoimmune liver disease. Med Clin North Am 1996 Sep; 80: 973–94

    PubMed  CAS  Google Scholar 

  87. Schalm SW, Summerskill WHJ, Go VLW. Prednisone for chronic active liver disease: pharmacokinetics, including conversion to prednisolone. Gastroenterology 1977 May; 72: 910–3

    PubMed  CAS  Google Scholar 

  88. Uribe M, Schalm SW, Summerskill WHJ, et al. Oral prednisone for chronic liver disease: dose responses and bioavailability studies. Gut 1978; 19: 1131–5

    PubMed  CAS  Google Scholar 

  89. Uribe M, Summerskill WHJ, Go VLW. Comparative serum prednisone and prednisolone concentrations following administration to patients with chronic active liver disease. Clin Pharmacokinet 1982; 7: 452–9

    PubMed  CAS  Google Scholar 

  90. Fauci AS, Dale DC. The effect of in vivo hydrocortisone on subpopulations of human lymphocytes. J Clin Invest 1974; 53: 240–6

    PubMed  CAS  Google Scholar 

  91. Yu DTY, Clements PJ, Paulus HE, et al. Human lymphocyte subpopulations: effect of corticosteroids. J Clin Invest 1974; 53: 565–71

    PubMed  CAS  Google Scholar 

  92. Frazer IH, Mackay IR. T lymphocyte subpopulations defined by two sets of monoclonal antibodies in chronic active hepatitis and systemic lupus erythematosus. Clin Exp Immunol 1982; 128: 95–9

    Google Scholar 

  93. Thomas HC, Brown D, Labrooy J, et al. T cell subsets in autoimmune and HBV-induced chronic liver disease, HBs antigen carriers with normal histology and primary biliary cirrhosis: a review of the abnormalities and the effects of treatment. J Clin Immunol 1982; 2 Suppl: 57S–60S

    PubMed  CAS  Google Scholar 

  94. Brown TE, Ahmed A, Filo RS, et al. The immunosuppressive mechanism of azathioprine: I. In vitro effect on lymphocyte function in the baboon. Transplantation 1976 Jan; 21: 27–35

    PubMed  CAS  Google Scholar 

  95. Colucci G, Colombo M, Del Ninno E, et al. In situ characterization by monoclonal antibodies of the mononuclear cell infiltrate in chronic active hepatitis. Gastroenterology 1983; 85: 1138–45

    PubMed  CAS  Google Scholar 

  96. Montano L, Aranguibel F, Boffill M, et al. An analysis of the composition of the inflammatory infiltrate in autoimmune and hepatitis B virus-induced chronic liver disease. Hepatology 1983; 3: 292–6

    PubMed  CAS  Google Scholar 

  97. Si L, Whiteside TL, Schade RR, et al. Studies of lymphocyte subpopulations in the liver tissue and blood of patients with chronic active hepatitis (CAH). J Clin Immunol 1983; 3: 408–19

    PubMed  CAS  Google Scholar 

  98. Czaja AJ, Wang KK, Shiels MT, et al. Oral pulse prednisone therapy after relapse of severe autoimmune chronic active hepatitis: a prospective randomized treatment trial evaluating clinical, biochemical, and lymphocyte subset responses. J Hepatol 1993; 17: 180–6

    PubMed  CAS  Google Scholar 

  99. Chase WF, Winn RE, Mayes GR. Oral pulse prednisone therapy in the treatment of HBsAg negative chronic active hepatitis. Gastroenterology 1982; 83: 1292–6

    PubMed  CAS  Google Scholar 

  100. Nouri-Aria KJ, Hegarty JE, Alexander GJM, et al. Effect of corticosteroids on suppressor-cell activity in ‘autoimmune’ and viral chronic active hepatitis. N Engl J Med 1982; 307: 1301–4

    PubMed  CAS  Google Scholar 

  101. Stellon AJ, Davies A, Compston J, et al. Bone loss in autoimmune chronic active hepatitis on maintenance corticosteroid therapy. Gastroenterology 1985 Nov; 89: 1078–83

    PubMed  CAS  Google Scholar 

  102. Wang KK, Czaja AJ. Prognosis of corticosteroid-treated hepatitis B surface antigen-negative chronic active hepatitis in postmenopausal women: a retrospective analysis. Gastroenterology 1989 Nov; 97: 1288–93

    PubMed  CAS  Google Scholar 

  103. Wolfhagen FHJ, van Buuren HR, den Ouden JW, et al. Cyclical etidronate in the prevention of bone loss in corticosteroid-treated primary biliary cirrhosis: a prospective, controlled pilot study. J Hepatol 1997; 26: 325–30

    PubMed  CAS  Google Scholar 

  104. Guanabens N, Pares A, Monegal A, et al. Etidronate versus fluoride for treatment of osteopenia in primary biliary cirrhosis: preliminary results after 2 years. Gastroenterology 1997 Jul; 113: 219–24

    PubMed  CAS  Google Scholar 

  105. Liberman UA, Weiss SR, Broil J, et al. Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. N Engl J Med 1995; 333: 1437–43

    PubMed  CAS  Google Scholar 

  106. Czaja AJ. Diagnosis, prognosis, and treatment of classical autoimmune chronic active hepatitis. In: Krawitt EL, Wiesner RH, editors. Autoimmune liver disease. New York: Raven Press, 1991: 143–66

  107. Czaja AJ, Davis GL, Ludwig J, et al. Complete resolution of inflammatory activity following corticosteroid treatment of HBsAg-negative chronic active hepatitis. Hepatology 1984; 4(4): 622–7

    PubMed  CAS  Google Scholar 

  108. De Pinho RA, Goldberg CS, Lefkowitch JH. Azathioprine and the liver: evidence favoring idiosyncratic, mixed cholestatichepatocellular injury in humans. Gastroenterology 1984; 86: 162–5

    Google Scholar 

  109. Read AE, Wiesner RH, LaBrecque DR, et al. Hepatic veno-occlusive disease associated with renal transplantation and azathioprine therapy. Ann Intern Med 1986 May; 104: 651–5

    PubMed  CAS  Google Scholar 

  110. Katzka DA, Saul SH, Jorkasky D, et al. Azathioprine and hepatic venocclusive disease in renal transplant patients. Gastroenterology 1986 Feb; 90: 448–54

    Google Scholar 

  111. Rosenkrantz JG, Githens JH, Cox SM, et al. Azathioprine (Imuran) and pregnancy. Am J Obstet Gynecol 1967 Feb; 97: 387–94

    PubMed  CAS  Google Scholar 

  112. Wang KK, Czaja AJ, Beaver SJ, et al. Extrahepatic malignancy following long-term immunosuppressive therapy of severe hepatitis B surface antigen-negative chronic active hepatitis. Hepatology 1989; 10(1): 39–43

    PubMed  CAS  Google Scholar 

  113. Penn I. Tumor incidence in allograft recipients. Transplant Proc 1979; 11: 1047–51

    PubMed  CAS  Google Scholar 

  114. Lewis GP, Jusko WJ, Burke CW, et al. Prednisone side-effects and serum protein levels: a collaborative study. Lancet 1971 Oct; II: 778–81

    Google Scholar 

  115. Uribe M, Go VLW, Kluge D. Prednisone for chronic active hepatitis: pharmacokinetics and serum binding in patients with chronic active hepatitis and steroid major side effects. J Clin Gastroenterol 1984 Aug; 6: 331–5

    PubMed  CAS  Google Scholar 

  116. Czaja AJ, Wolf AM, Baggenstoss AH. Laboratory assessment of severe chronic active liver disease (CALD): correlation of serum transaminase and gamma globulin levels with histologic features. Gastroenterology 1981 Apr; 80: 687–92

    PubMed  CAS  Google Scholar 

  117. Czaja AJ, Ammon HV, Summerskill WHJ. Clinical features and prognosis of severe chronic active liver disease (CALD) after corticosteroid-induced remission. Gastroenterology 1980 Mar; 78: 518–23

    PubMed  CAS  Google Scholar 

  118. Czaja AJ, Ludwig J, Baggenstoss AH, et al. Corticosteroid-treated chronic active hepatitis in remission. Uncertain prognosis of chronic persistent hepatitis. N Engl J Med 1981 Jan; 304: 5–9

    CAS  Google Scholar 

  119. Czaja AJ, Beaver SJ, Shiels MT. Sustained remission following corticosteroid therapy of severe HBsAg-negative chronic active hepatitis. Gastroenterology 1987 Jan; 92(1): 215–9

    PubMed  CAS  Google Scholar 

  120. Czaja AJ, Magrin S, Fabiano C, et al. Hepatitis C virus infection as a determinant of behavior in type 1 autoimmune hepatitis. Dig Dis Sci 1995 Jan; 40: 33–40

    PubMed  CAS  Google Scholar 

  121. Czaja AJ. The variant forms of autoimmune hepatitis. Ann Intern Med 1996 Oct; 125: 588–98

    PubMed  CAS  Google Scholar 

  122. Hegarty JE, Nouri-Aria KT, Portmann B, et al. Relapse following treatment withdrawal in patients with autoimmune chronic active hepatitis. Hepatology 1983; 3: 685–9

    PubMed  CAS  Google Scholar 

  123. Czaja AJ. Low dose corticosteroid therapy after multiple relapses of severe HBsAg-negative chronic active hepatitis. Hepatology 1990 Jun; 11: 1044–9

    PubMed  CAS  Google Scholar 

  124. Stellon AJ, Keating JJ, Johnson PJ, et al. Maintenance of remission in autoimmune chronic active hepatitis with azathioprine after corticosteroid withdrawal. Hepatology 1988; 8: 781–4

    PubMed  CAS  Google Scholar 

  125. Johnson PJ, McFarlane IG, Williams R. Azathioprine for long-term maintenance of remission in autoimmune hepatitis. N Engl J Med 1995 Oct; 333: 958–63

    PubMed  CAS  Google Scholar 

  126. Davis GL, Czaja AJ, Ludwig J. Development and prognosis of histologie cirrhosis in corticosteroid-treated HBsAg-negative chronic active hepatitis. Gastroenterology 1984 Dec; 87: 1222–7

    PubMed  CAS  Google Scholar 

  127. Runyon BA. Exquisite sensitivity to small decrements in corticosteroid dose in autoimmune chronic active hepatitis. J Clin Gastroenterol 1987 Oct; 9(5): 541–2

    PubMed  CAS  Google Scholar 

  128. Schalm SW, Ammon HV, Summerskill WHJ. Failure of customary treatment in chronic active liver disease: causes and management. Ann Clin Res 1976; 8: 221–7

    PubMed  CAS  Google Scholar 

  129. Ben Ari Z, Mehta A, Lennard L, et al. Azathioprine-induced myelosuppression due to thiopurine methyltransferase deficiency in apatient with autoimmune hepatitis. J Hepatol 1995; 23: 351–4

    PubMed  CAS  Google Scholar 

  130. Yates CR, Krynetski EY, Loennechen T, et al. Molecular diagnosis of thiopurine S-methyltransferase deficiency: genetic basis for azathioprine and mercaptopurine intolerance. Ann Intern Med 1997 Apr; 126: 608–14

    PubMed  CAS  Google Scholar 

  131. Sempoux C, Horsmans Y, Lerut J, et al. Acute lobular hepatitis as the first manifestation of recurrent autoimmune hepatitis after orthotopic liver transplantation. Liver 1997; 17: 311–5

    PubMed  CAS  Google Scholar 

  132. Neuberger J, Portmann B, Calne R, et al. Recurrence of autoimmune chronic active hepatitis following orthotopic liver grafting. Transplantation 1984; 37: 363–5

    PubMed  CAS  Google Scholar 

  133. Wright HL, Bou-Abboud CF, Hassanein T, et al. Disease recurrence and rejection following liver transplantation for autoimmune chronic active liver disease. Transplantation 1992; 53: 136–9

    PubMed  CAS  Google Scholar 

  134. Czaja AJ. Chronic active hepatitis: the challenge for a new nomenclature. Ann Intern Med 1993 Sept; 119(6): 510–7

    PubMed  CAS  Google Scholar 

  135. Czaja AJ. Frequency and nature of the variant syndromes of autoimmune liver disease. Hepatology 1998 Aug; 28: 360–5

    PubMed  CAS  Google Scholar 

  136. Czaja AJ, Carpenter HA, Santrach PJ, et al. The nature and prognosis of severe cryptogenic chronic active hepatitis. Gastroenterology 1993 Jun; 104(6): 1755–61

    PubMed  CAS  Google Scholar 

  137. Hegarty JE, Nouri-Aria KT, Eddieston ALWF, et al. Controlled trial of a thymic hormone extract (thymostimulin) in ‘autoimmune’ chronic active hepatitis. Gut 1984 Mar; 25: 279–83

    PubMed  CAS  Google Scholar 

  138. Jenkins PJ, Portmann BP, Eddieston ALWF, et al. Use of polyunsaturated phosphatidyl choline in HBsAg negative chronic active hepatitis: results of prospective double-blind controlled trial. Liver 1982; 2: 77–81

    PubMed  CAS  Google Scholar 

  139. VanThiel DH, Wright H, Carroll P, et al. Tacrolimus: a potential new treatment for autoimmune chronic active hepatitis: results of an open-label preliminary trial. Am J Gastroenterol 1995 May; 90: 771–6

    PubMed  Google Scholar 

  140. Thomson AW. FK-506: profile of an important new immuno-suppressant. Transplant Rev 1990; 4: 1–13

    Google Scholar 

  141. Frizell E, Abraham A, Doolittle M, et al. FK506 enhances fibrogenesis in in vitro and in vivo models of liver fibrosis in rats. Gastroenterology 1994 Aug; 107: 492–8

    PubMed  CAS  Google Scholar 

  142. Clissold SP, Heel RC. Budesonide: a preliminary review of its pharmacodynamic properties and therapeutic efficacy in asthma and rhinitis. Drugs 1984; 28: 485–518

    PubMed  CAS  Google Scholar 

  143. Danielsson A, Prytz H. Oral budesonide for treatment of autoimmune chronic active hepatitis. Aliment Pharmacol Ther 1994; 8: 585–90

    PubMed  CAS  Google Scholar 

  144. Bruno A, Cavallo-Perin P, et al. Deflazacort vs prednisone: effect on blood glucose control in insulin-treated diabetics. Arch Intern Med 1987 Apr; 147: 679–80

    PubMed  CAS  Google Scholar 

  145. Rebollo J, Pinar A, Utrilla MC, et al. Deflazacort in the maintenance therapy of autoimmune hepatitis [abstract]. Hepatology 1996 Oct; 24: 236A

    Google Scholar 

  146. Mistilis SP, Vickers CR, Darroch MH, et al. Cyclosporin, a new treatment for autoimmune chronic active hepatitis. Med J Aust 1985 Nov; 143: 463–5

    PubMed  CAS  Google Scholar 

  147. Hyams JS, Ballow M, Leichtner AM. Cyclosporine treatment of autoimmune chronic active hepatitis. Gastroenterology 1987 Oct; 93: 890–3

    PubMed  CAS  Google Scholar 

  148. Minuk GY Cyclosporin A in nontransplant-related liver disease. Am J Gastroenterol 1989 Nov; 84: 1345–50

    PubMed  CAS  Google Scholar 

  149. Sherman KE, Narkewicz M, Pinto PC. Cyclosporine in the management of corticosteroid-resistant type 1 autoimmune chronic active hepatitis. J Hepatol 1994 Dec; 21: 1040–7

    PubMed  CAS  Google Scholar 

  150. Jackson LD, Song E. Cyclosporin in the treatment of corticosteroid resistant autoimmune chronic active hepatitis. Gut 1995 Mar; 36: 459–61

    PubMed  CAS  Google Scholar 

  151. Pratt DS, Flavin DP, Kaplan MM. The successful treatment of autoimmune hepatitis with 6-mercaptopurine after failure with azathioprine. Gastroenterology 1996 Jan; 110: 271–4

    PubMed  CAS  Google Scholar 

  152. Yarze JC, Herlihy KJ, Fritz HP, et al. Azathioprine and 6-mercaptopurine and autoimmune hepatitis. Gastroenterology 1996 Jun; 110: 2027

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA

    Albert J. Czaja

Authors
  1. Albert J. Czaja
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Czaja, A.J. Drug Therapy in the Management of Type 1 Autoimmune Hepatitis. Drugs 57, 49–68 (1999). https://doi.org/10.2165/00003495-199957010-00005

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-199957010-00005

Keywords

Search

Navigation