Summary
Prednisone alone or in combination with azathioprine is effective in the treatment of patients with severe autoimmune hepatitis. The major consequences of therapy are amelioration of symptoms and enhancement of immediate survival. Patients who are most likely to realise these benefits must be rigorously selected for treatment, as the diagnosis of autoimmune hepatitis per se does not compel therapy.
Autoimmune hepatitis is not an easy diagnosis; institution of corticosteroid therapy is not a simple decision; and demonstration of a favourable response to initial therapy is not the end-point of treatment.
Cure of the disease and prevention of cirrhosis should not be the primary goals of treatment, as the consistent procurement of these results has not been demonstrated. Suboptimal responses to treatment are common and guidelines for the confident management of these outcomes have not been fully developed. Relapse after drug withdrawal is frequent and its management requires highly individualised care. Liver transplantation should be considered only after the response to corticosteroid treatment has been assessed. Tacrolimus (FK-506), ursodeoxycholic acid and cytoprotective agents have promise as primary or adjunctive therapies, but their efficacy has not been established.
Similar content being viewed by others
References
Bearn AG, Kunkel HG, Slater RJ. The problem of chronic liver disease in young women. Am J Med 1956; 21: 3–15
Czaja AJ. Current problems in the diagnosis and management of chronic active hepatitis. Mayo Clin Proc 1981; 56: 311–23
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
Johnson PJ, McFarlane IG, Alvarez F, et al. Meeting report: International Autoimmune Hepatitis Group. Hepatology 1993; 18: 998–1005
Magrin S, Craxi A, Fiorentino G, et al. Is autoimmune chronic active hepatitis a HCV-related disease? J Hepatol 1991; 13: 56–60
Magrin S, Craxi A, Fabiano C, et al. Hepatitis C virus replication in ‘autoimmune’ chronic hepatitis. J Hepatol 1991; 13: 364–7
Vento S, DiPerri G, Garofano T, et al. Hazards of interferon therapy for HBV-seronegative chronic hepatitis. Lancet 1989; 2: 926
Papo T, Marcellin P, Bemuau J, et al. Autoimmune chronic hepatitis exacerbated by alpha-interferon. Ann Intern Med 1992; 116: 51–3
Shindo M, DiBisceglie AM, Hoofnagle JH. Acute exacerbation of liver disease during interferon alfa therapy for chronic hepatitis C. Gastroenterology 1992; 102: 1406–8
Czaja AJ. Natural history, clinical features, and treatment of autoimmune hepatitis. Semin Liver Dis 1984; 4: 1–12
Czaja AJ, Carpenter HA, Santrach PJ, et al. The nature and prognosis of severe cryptogenic chronic active hepatitis. Gastroenterology 1993; 104: 1755–61
Czaja AJ. Chronic active hepatitis: the challenge of a new nomenclature. Ann Intern Med 1993; 119: 510–7
Amontree JS, Stuart TD, Bredfeldt JE. Autoimmune chronic active hepatitis masquerading as acute hepatitis. J Clin Gastroenterol 1989; 11: 303–7
Davis GL, Czaja AJ, Baggenstoss AH, et al. Prognostic and therapeutic implications of extreme serum aminotransferase elevation in chronic active hepatitis. Mayo Clin Proc 1982; 57: 303–9
Crapper RM, Bhathal PS, Mackay IR, et al. ‘Acute’ autoimmune hepatitis. Digestion 1986; 34: 216–25
Porta G, Da Costa Gayotto LC, Alvarez F. Anti-liver-kidney microsome antibody-positive autoimmune hepatitis presenting as fulminant liver failure. J Ped Gastroenterol Nutr 1990; 11: 138–40
Czaja AJ. Autoimmune chronic active hepatitis — a specific entity? The negative argument. J Gastroenterol Hepatol 1990; 5: 343–51
Czaja AJ. Diagnosis and treatment of chronic hepatitis. Compr Ther 1984; 10: 58–63
Perdigoto R, Carpenter HA, Czaja AJ. Frequency and significance of chronic ulcerative colitis in severe corticosteroid-treated autoimmune hepatitis. J Hepatol 1992; 14: 325–31
Maddrey WC. Subdivisions of idiopathic autoimmune chronic active hepatitis. Hepatology 1987; 7: 1372–5
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; 85: 713–7
Czaja AJ, Carpenter HA, Santrach PJ, et al. Genetic predispositions for the immunological features of chronic active hepatitis. Hepatology 1993; 18: 816–22
Czaja AJ, Carpenter HA, Santrach PJ, et al. Evidence against hepatitis viruses as important causes of severe autoimmune hepatitis in the United States. J Hepatol 1993; 18: 342–52
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 1990; 13: 701–6
Czaja AJ, Carpenter HA, Santrach PJ, et al. Significance of HLA DR4 in type 1 autoimmune hepatitis. Gastroenterology 1993; 105: 1502–7
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; 7: 1333–9
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; 88: 1370–8
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
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; 1: 292–4
Czaja AJ, Carpenter HA, Manns MP. Antibodies to soluble liver antigen, P450 IID6 and mitochondrial complexes in chronic hepatitis. Gastroenterology 1993; 105: 1522–8
Stechemesser E, Klein R, Berg PA. Characterization and clinical relevance of liver-pancreas antibodies in autoimmune hepatitis. Hepatology 1993; 18: 1–9
Geall MG, Schoenfield LJ, Summerskill WHJ. Classification and treatment of chronic active liver disease. Gastroenterology 1972; 63: 458–65
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; 63: 820–33
Schalm SW, Korman MG, Summerskill WHJ, et al. Severe chronic active liver disease: prognostic significance of initial morphologic patterns. Am J Dig Dis 1977; 22: 973–80
Murray-Lyon IM, Stem RB, Williams R. Controlled trial of prednisone and azathioprine in active chronic hepatitis. Lancet 1973; 1: 735–7
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
Thaler H. The natural history of chronic hepatitis. In: Schaffner F, Sherlock S, Leevy CM, editors. The liver and its diseases. New York: Stratton International Medical Books, 1974: 207–15
Kemeny MJ, O’Hanlon G, Gregory PB. Asymptomatic chronic active hepatitis-prognosis and treatment [abstract]. Gastroenterology 1984; 86: 1325
Mistilis SP, Skyring AP, Blackburn CRB. Natural history of active chronic hepatitis: I. Clinical features, course, diagnostic criteria, morbidity, mortality, and survival. Australas Ann Med 1968; 17: 214–23
Burroughs AK, Bassendine MF, Thomas HC, et al. Primary liver cell cancer in autoimmune chronic liver disease. BMJ 1981; 282: 273
Jakobovits AW, Gibson PR, Dudley FJ. Primary liver cell carcinoma complicating autoimmune chronic active hepatitis. Dig Dis Sci 1981; 25: 694–9
Cook GC, Mulligan R, Sherlock S. Controlled prospective trial of corticosteroid therapy in active chronic hepatitis. Q J Med 1971; 40: 159–85
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
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
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: 622–7
Penn I. Tumor incidence in allograft recipients. Transplant Proc 1979; 11: 1047–51
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: 39–43
Wang KK, Czaja AJ. Prognosis of corticosteroid-treated hepatitis B surface antigen-negative chronic active hepatitis in postmenopausal women: a retrospective analysis. Gastroenterology 1989; 97: 1288–93
Czaja AJ, Ammon HV, Summerskill WHJ. Clinical features and prognosis of severe chronic active liver disease (CALD) after corticosteroid-induced remission. Gastroenterology 1980; 78: 518–23
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; 304: 5–9
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
Czaja AJ, Beaver SJ, Shiels MT. Sustained remission after corticosteroid therapy of severe hepatitis B surface antigen-negative chronic active hepatitis. Gastroenterology 1987; 92: 215–9
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; 80: 687–92
Davis GL, Czaja AJ, Ludwig J. Development and prognosis of histologic cirrhosis in corticosteroid-treated HBsAg-negative chronic active hepatitis. Gastroenterology 1984; 87: 1222–7
Czaja AJ, Wolf AM, Summerskill WHJ. Development and early prognosis of esophageal varices in severe chronic active liver disease (CALD) treated with prednisone. Gastroenterology 1979; 77: 629–33
Schvarcz R, Glaumann H, Weiland O. Survival and histological resolution of fibrosis in patients with autoimmune chronic active hepatitis. J Hepatol 1993; 18: 15–23
Wang KK, Czaja AJ. Hepatocellular cancer in corticosteroid-treated severe autoimmune chronic active hepatitis. Hepatology 1988; 8: 1679–83
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
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; 15: 215–21
Czaja AJ, Rakela J, Ludwig J. Features reflective of early prognosis in corticosteroid-treated severe autoimmune chronic active hepatitis. Gastroenterology 1988; 95: 448–53
Czaja AJ, Rakela J, Hay JE, et al. Clinical and prognostic implications of human leukocyte antigen B8 in corticosteroid-treated severe autoimmune chronic active hepatitis. Gastroenterology 1990; 98: 1587–93
Opelz G, Vogten AJM, Summerskill WHJ, et al. HLA determinants in chronic active liver disease: possible relation of HLA-Dw3 to prognosis. Tissue Antigens 1977; 9: 36–40
Czaja AJ. Low dose corticosteroid therapy after multiple relapses of severe HBsAg-negative chronic active hepatitis. Hepatology 1990; 11: 1044–9
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
Chase WF, Winn RE, Mayes GR. Oral pulse prednisone therapy in the treatment of HBsAg negative chronic active hepatitis. Gastroenterology 1982; 83: 1292–6
Hyams JS, Ballow M, Leichtner AM. Cyclosporine treatment of autoimmune chronic active hepatitis. Gastroenterology 1987; 93: 890–3
Mistilis SP, Viekers CR, Darroch MH, et al. Cyclosporin, a new treatment for autoimmune chronic active hepatitis. Med J Australia 1985; 143: 463–5
Faulds D, Goa KL, Benfield P. Cyclosporin: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in immunoregulatory disorders. Drugs 1993; 45: 953–1040
Neuberger J, Portmann B, Calne R, et al. Recurrence of autoimmune chronic active hepatitis following orthotopic liver grafting. Transplantation 1984; 37: 363–5
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
Todros L, Touscoz G, D’Urso N, et al. Hepatitis C virus-related chronic liver disease with autoantibodies to liver-kidney microsomes (LKM): clinical characterization from idiopathic LKM-positive disorders. J Hepatol 1991; 13: 128–31
Garson JA, Lenzi M, Ring C, et al. Hepatitis C viraemia in adults with type 2 autoimune hepatitis. J Med Virol 1991; 34: 223–6
Czaja AJ, Taswell HF, Rakela J, et al. Duration and specificity of antibodies to hepatitis C virus in chronic active hepatitis. Gastroenterology 1992; 102: 1675–9
Peters DH, Fitton A, Plosker GL, et al. Tacrolimus: a review of its pharmacology, and therapeutic potential in hepatic and renal transplantation. Drugs 1993; 46: 746–94
Van Thiel DH, Wright H, Carroll P, et al. FK 506 in the treatment of autoimmune chronic active hepatitis: preliminary results [abstract]. Am J Gastroenterol 1992; 87: 1309
Crosignani A, Battezzati PM, Setchell KDR, et al. Effects of ursodeoxycholic acid on serum liver enzymes and bile acid metabolism in chronic active hepatitis: a dose-response study. Hepatology 1991; 13: 339–44
Heuman DM, Mills AS, McCall J, et al. Conjugates of ursodeoxycholate protect against cholestasis and hepatocellular necrosis caused by more hydrophobic bile salts: in vivo studies in the rat. Gastroenterology 1991; 100: 203–11
Marteau P, Chazouilleres O, Myara A, et al. Effect of chronic administration of ursodeoxycholic acid on the ileal absorption of endogenous bile acids in man. Hepatology 1990; 12: 1206–8
Poo JL, Feldmann G, Erlinger S, et al. Ursodeoxycholic acid limits liver histologic alterations and portal hypertension induced by bile duct ligation in the rat. Gastroenterology 1992; 102: 1752–9
Calmus Y, Gane P, Rouger P, et al. Hepatic expression of class I and class II major histocompatibility complex molecules in primary biliary cirrhosis: effect of ursodeoxycholic acid. Hepatology 1990; 11: 12–5
Jenkins PJ, Portmann BP, Eddleston 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
Miracco A, Iodice G, Peluso C, et al. Arginine thiazolidinecarboxylate in the treatment of chronic active hepatitis: double-blind comparison with placebo. J Int Med Res 1984; 12: 35–9
Hegarty JE, Nouri-Aria KT, Eddleston ALWF, et al. Controlled trial of a thymic hormone extract (thymostimulin) in ‘autoimmune’ chronic active hepatitis. Gut 1984; 25: 279–83
Mutchnick MG, Appelman HD, Chung HT, et al. Thymosin treatment of chronic hepatitis B: a placebo-controlled pilot trial. Hepatology 1991; 14: 409–15
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Czaja, A.J. Autoimmune Hepatitis. Clin. Immunother. 1, 413–429 (1994). https://doi.org/10.1007/BF03259034
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03259034