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Semin Liver Dis 2002; 22(4): 317-324
DOI: 10.1055/s-2002-35702
Copyright © 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Definition and Classification of Autoimmune Hepatitis

Ian G. McFarlane
  • Institute of Liver Studies, King's College Hospital, London, United Kingdom
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Publikationsdatum:
25. November 2002 (online)

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ABSTRACT

Autoimmune hepatitis (AIH) has been defined as ``an unresolving, predominantly periportal hepatitis, usually with hypergammaglobulinemia and tissue autoantibodies, which is responsive to immunosuppressive therapy in most cases.'' It is a relatively rare disorder, with a preponderance of female patients, that can present at any age (although onset in most cases is after 40 years of age). There are no features that are pathognomonic of the condition. Diagnosis requires careful exclusion of other causes of liver disease together with the finding of a suggestive pattern of clinical and laboratory abnormalities. The marked heterogeneity of AIH with respect to presenting features, severity of disease, and response to therapy has led to several proposals for classification of the disease according to (mainly) immunologic parameters. These schemata may assist in diagnosis, and some may define different pathogenetic subgroups of the disease, but their utility for assessing prognosis or planning treatment strategies for the individual patient is still uncertain.

KEYWORDS

Autoimmunity - autoantibodies - chronic liver disease

REFERENCES

  • 1 Waldenström J. Leber, blutproteine und Nahrungsweiss.  Deutsch Gesellschaft Z Verdau Stoffwechselkr . 1950;  15 113-119
    PubMedGoogle Scholar
  • 2 Mackay I R, Tait B D. The history of autoimmune hepatitis. In: Nishioka M, Toda G, Zeniya M, eds. Autoimmune Hepatitis Amsterdam: Elsevier 1994: 3-23
    Google Scholar
  • 3 McFarlane I G, Williams R. Historical overview. In: McFarlane IG, Williams R, eds. Molecular Basis of Autoimmune Hepatitis Austin, TX: RG Landes 1996: 1-21
    Google Scholar
  • 4 Heneghan M A, McFarlane I G. Current and novel immunotherapy for autoimmune hepatitis.  Hepatology . 2002;  35 7-13
    CrossrefPubMedGoogle Scholar
  • 5 Popper H, Paronetto F, Schaffner F. Immune processes in the pathogenesis of liver disease.  Ann NY Acad Sci . 1965;  124 781-799
    PubMedGoogle Scholar
  • 6 International Group. Acute and chronic hepatitis revisited.  Lancet . 1977;  ii 914-919
    PubMedGoogle Scholar
  • 7 Ludwig J. The nomenclature of chronic active hepatitis: an obituary.  Gastroenterology . 1993;  105 274-278
    PubMedGoogle Scholar
  • 8 Czaja A J. Current problems in the diagnosis and managment of chronic active hepatitis.  Mayo Clin Proc . 1981;  56 311-323
    PubMedGoogle Scholar
  • 9 Czaja A J, Ludwig J, Baggenstoss A H, Wolf A. Corticosteroid-treated chronic active hepatitis in remission: uncertain prognosis of chronic persistent hepatitis.  N Engl J Med . 1981;  304 5-9
    PubMedGoogle Scholar
  • 10 Ludwig J. Morphology of chronic active hepatitis: differential diagnosis and therapeutic implications. In: Czaja AJ, Dickson ER, eds. Chronic Active Hepatitis: The Mayo Clinic Experience New York: Marcel Dekker 1986: 83-104
    Google Scholar
  • 11 Soloway R D, Summerskill W HJ, Baggenstoss A H. Clinical, biochemical and histological remission of severe chronic active liver disease: a controlled study of treatments and early prognosis.  Gastroenterology . 1972;  63 820-833
    PubMedGoogle Scholar
  • 12 Hay J E, Czaja A J, Rakela J. The nature of unexplained chronic aminotransferase elevations of a mild to moderate degree in asymptomatic patients.  Hepatology . 1989;  9 193-197
    PubMedGoogle Scholar
  • 13 McFarlane I G. Clinical spectrum and heterogeneity of autoimmune hepatitis: an overview. In: Meyer zum Büschenfelde K-H, Hoofnagle JH, Manns M, eds. Immunology and Liver London: Kluwer 1993: 179-192
    Google Scholar
  • 14 Plotz P H. Asymptomatic chronic active hepatitis.  Gastroenterology . 1975;  68 1629-1630
    PubMedGoogle Scholar
  • 15 Lefkowitch J H, Apfelbaum T F, Weinberg L. Acute liver biopsy lesions in early autoimmune (``lupoid'') chronic active hepatitis.  Liver . 1984;  4 379-386
    PubMedGoogle Scholar
  • 16 Nikias G A, Batts K P, Czaja A J. The nature and prognostic implications of autoimmune hepatitis with an acute presentation.  J Hepatol . 1994;  21 866-871
    CrossrefPubMedGoogle Scholar
  • 17 Burgart L J, Batts K P, Ludwig J, Nikias G A, Czaja A J. Recent-onset autoimmune hepatitis. Biopsy findings and clinical correlations.  Am J Surg Pathol . 1995;  19 699-708
    PubMedGoogle Scholar
  • 18 McFarlane I G. Autoimmunity and hepatotropic viruses.  Semin Liver Dis . 1991;  11 223-233
    PubMedGoogle Scholar
  • 19 Johnson P J, McFarlane I G. Meeting report: International Autoimmune Hepatitis Group.  Hepatology . 1993;  18 998-1005
    CrossrefPubMedGoogle Scholar
  • 20 Desmet V J, Gerber M, Hoofnagle J H, Manns M, Scheuer P J. Classification of chronic hepatitis: diagnosis, grading and staging.  Hepatology . 1994;  19 1513-1520
    CrossrefPubMedGoogle Scholar
  • 21 Ludwig J, McFarlane I G, Rakela J. International Working Party Report: Terminology of chronic hepatitis.  Am J Gastroenterol . 1995;  90 181-189
    PubMedGoogle Scholar
  • 22 Mackay I R. Towards diagnostic criteria for autoimmune hepatitis.  Hepatology . 1993;  18 1006-1008
    PubMedGoogle Scholar
  • 23 International Autoimmune Hepatitis Group. Report: review of criteria for diagnosis of autoimmune hepatitis.  J Hepatol . 1999;  31 929-938
    CrossrefPubMedGoogle Scholar
  • 24 Heneghan M A, Norris S, O'Grady J G, Harrison P M, McFarlane I G. Management and outcome of pregnancy in autoimmune hepatitis.  Gut . 2001;  48 97-102
    CrossrefPubMedGoogle Scholar
  • 25 Czaja A J. Behaviour and significance of autoantibodies in type 1 autoimmune hepatitis.  J Hepatol . 1999;  30 394-401
    CrossrefPubMedGoogle Scholar
  • 26 Czaja A J, Cassani F, Cataleta M, Valentini P, Bianchi F B. Antinuclear antibodies and patterns of nuclear immunofluorescence in type 1 autoimmune hepatitis.  Dig Dis Sci . 1997;  42 1688-1696
    CrossrefPubMedGoogle Scholar
  • 27 McFarlane I G. The relationship between autoimmune markers and different clinical syndromes in autoimmune hepatitis.  Gut . 1998;  42 599-602
    PubMedGoogle Scholar
  • 28 Czaja A J, Cassani F, Cataleta M, Valentini P, Bianchi F B. Frequency and significance of antibodies to actin in type 1 autoimmune hepatitis.  Hepatology . 1996;  24 1068-1073
    CrossrefPubMedGoogle Scholar
  • 29 Terjung B, Worman H J. Anti-neutrophil antibodies in primary sclerosing cholangitis.  Best Pract Res Clin Gastroenterol . 2001;  15 629-642
    CrossrefPubMedGoogle Scholar
  • 30 Manns M P, Griffin K J, Sullivan K F. LKM-1 autoantibodies recognize a short linear sequence in P450IID6, a cytochrome P-450 monooxygenase.  J Clin Invest . 1991;  88 1370-1378
    PubMedGoogle Scholar
  • 31 Cassani F, Cataleta M, Valentini P. Serum autoantibodies in chronic hepatitis C: comparison with autoimmune hepatitis and impact on the disease profile.  Hepatology . 1997;  26 561-566
    PubMedGoogle Scholar
  • 32 Duchini A, McHutchison J G, Pockros P J. LKM-positive autoimmune hepatitis in the western United States: a case series.  Am J Gastroenterol . 2000;  95 3238-3241
    CrossrefPubMedGoogle Scholar
  • 33 Kenny R P, Czaja A J, Ludwig J, Dickson E R. Frequency and significance of antimitochondrial antibodies in severe chronic active hepatitis.  Dig Dis Sci . 1986;  31 705-711
    CrossrefPubMedGoogle Scholar
  • 34 Gregorio G V, Portmann B, Mowat A P, Vergani D, Mieli-Vergani G. A 12-year-old girl with antimitochondrial antibody-positive autoimmune hepatitis.  J Hepatol . 1997;  27 751-754
    CrossrefPubMedGoogle Scholar
  • 35 McFarlane B M, McSorley C G, Vergani D, McFarlane I G, Williams R. Serum autoantibodies reacting with the hepatic asialoglycoprotein receptor (hepatic lectin) in acute and chronic liver disorders.  J Hepatol . 1986;  3 196-205
    CrossrefPubMedGoogle Scholar
  • 36 Treichel U, McFarlane B M, Seki T. Demographics of anti-asialo-glycoprotein receptor autoantibodies in autoimmune hepatitis.  Gastroenterology . 1994;  107 799-804
    PubMedGoogle Scholar
  • 37 Czaja A J, Pfeifer K D, Decker R H, Vallari A S. Frequency and significance of antibodies to asialoglycoprotein receptor in type 1 autoimmune hepatitis.  Dig Dis Sci . 1996;  41 1733-1740
    PubMedGoogle Scholar
  • 38 Abuaf N, Johanet C, Chretien P. Characterization of the liver cytosol antigen type 1 reacting with autoantibodies in chronic active hepatitis.  Hepatology . 1992;  16 892-898
    PubMedGoogle Scholar
  • 39 Han S, Tredger M, Gregorio G V, Mieli-Vergani G, Vergani D. Anti-liver cytosolic antigen type 1 (LC1) antibodies in childhood autoimmune liver disease.  Hepatology . 1995;  21 58-62
    CrossrefPubMedGoogle Scholar
  • 40 Lenzi M, Manotti P, Muratori L. Liver cytosolic 1 antigen-antibody system in type 2 autoimmune hepatitis and hepatitis C virus infection.  Gut . 1995;  36 749-754
    PubMedGoogle Scholar
  • 41 Lapierre P, Hajoui O, Homberg J C, Alvarez F. Formiminotransferase cyclodeaminase is an organ-specific autoantigen recognized by sera of patients with autoimmune hepatitis.  Gastroenterology . 1999;  116 643-649
    PubMedGoogle Scholar
  • 42 Wies I, Brunner S, Henninger J. Identification of target antigen for SLA/LP autoantibodies in autoimmune hepatitis.  Lancet . 2000;  355 1510-1515
    CrossrefPubMedGoogle Scholar
  • 43 Costa M, Rodriguez-Sanchez J L, Czaja A J, Gelpi C. Isolation and characterization of cDNA encoding the antigenic protein of the human tRNP((Ser)Sec) complex recognized by autoantibodies from patients with type-1 autoimmune hepatitis.  Clin Exp Immunol . 2000;  121 364-374
    CrossrefPubMedGoogle Scholar
  • 44 Czaja A J, Donaldson P T, Lohse A W. Antibodies to soluble liver antigen/liver pancreas and HLA risk factors for type 1 autoimmune hepatitis.  Am J Gastroenterol . 2002;  97 413-419
    CrossrefPubMedGoogle Scholar
  • 45 Donaldson P T, Doherty D G, Hayllar K M. Susceptibility to autoimmune chronic active hepatitis: human leukocyte antigens DR4 and A1-B8-DR3 are independent risk factors.  Hepatology . 1991;  13 701-706
    CrossrefPubMedGoogle Scholar
  • 46 Toda G, Zeniya M, Watanabe R. Present status of autoimmune hepatitis in Japan-correlating the characteristics with international criteria in an area with a high rate of HCV infection.  J Hepatol . 1997;  26 1207-1212
    CrossrefPubMedGoogle Scholar
  • 47 Bittencourt P L, Goldberg A C, Cancado E LR. Genetic heterogeneity in susceptibility to autoimmune hepatitis types 1 and 2.  Am J Gastroenterol . 1999;  94 1906-1913
    CrossrefPubMedGoogle Scholar
  • 48 Pando M, Larriba J, Fernandez G C. Pediatric and adult forms of type 1 autoimmune hepatitis in Argentina: evidence for differential genetic disposition.  Hepatology . 1999;  20 1374-1380
    PubMedGoogle Scholar
  • 49 Strettell M D, Donaldson P T, Thomson L J. Allelic basis for HLA-encoded susceptibility to type 1 autoimmune hepatitis.  Gastroenterology . 1997;  112 2028-2035
    PubMedGoogle Scholar
  • 50 Czaja A J, Strettell M D, Thomson L J. Associations between alleles of the major histocompatibility complex and type 1 autoimmune hepatitis.  Hepatology . 1997;  25 317-323
    PubMedGoogle Scholar
  • 51 Scully L J, Toze C, Sengar D PS. Early-onset autoimmune hepatitis is associated with a C4A gene deletion.  Gastroenterology . 1993;  104 1478-1484
    PubMedGoogle Scholar
  • 52 Vergani D, Wells L, Larcher V F. Genetically determined low C4: a predisposing factor to autoimmune chronic active hepatitis.  Lancet . 1985;  ii 294-298
    PubMedGoogle Scholar
  • 53 Doherty D G, Underhill J A, Donaldson P T. Polymorphism in the human complement C4 genes and susceptibility to autoimmune hepatitis.  Autoimmunity . 1994;  18 243-249
    PubMedGoogle Scholar
  • 54 Gregorio G V, Portmann B, Karani J. Autoimmune hepatitis/sclerosing cholangitis overlap syndrome in childhood: a 16-year prospective study.  Hepatology . 2001;  33 544-553
    CrossrefPubMedGoogle Scholar
  • 55 Homberg J C, Abuaf N, Bernard O. Chronic active hepatitis associated with antiliver/kidney microsome antibody type 1: a second type of ``autoimmune'' hepatitis.  Hepatology . 1987;  7 1333-1339
    PubMedGoogle Scholar
  • 56 Manns M, Gerken G, Kyriatsoulis A, Staritz M, Meyer zum Buschenfelde H K. Characterisation of a new subgroup of autoimmune chronic active hepatitis by autoantibodies against a soluble liver antigen.  Lancet . 1987;  i 292-294
    PubMedGoogle Scholar
  • 57 Czaja A J, Carpenter H A, Manns M P. Antibodies to soluble liver antigen, P450IID6, and mitochondrial complexes in chronic hepatitis.  Gastroenterology . 1993;  105 1522-1528
    PubMedGoogle Scholar
  • 58 Kanzler S, Weidemann C, Gerken G. Clinical significance of autoantibodies to soluble liver antigen in autoimmune hepatitis.  J Hepatol . 1999;  31 635-640
    CrossrefPubMedGoogle Scholar
  • 59 Gregorio G V, Portmann B, Reid F. Autoimmune hepatitis in childhood: a 20-year experience.  Hepatology . 1997;  25 541-547
    CrossrefPubMedGoogle Scholar
  • 60 Muratori L, Parola M, Ripalti A. Liver/kidney microsomal antibody type 1 targets CYP2D6 on hepatocyte plasma membrane.  Gut . 2000;  46 553-561
    CrossrefPubMedGoogle Scholar
  • 61 Herkel J, Heidrich B, Nieraad N. Fine specificity of autoantibodies to soluble liver antigen and liver/pancreas.  Hepatology . 2002;  35 403-408
    CrossrefPubMedGoogle Scholar
  • 62 McFarlane I G. Lessons about antibodies in autoimmune hepatitis.  Lancet . 2000;  355 1475-1476
    CrossrefPubMedGoogle Scholar
  • 63 Czaja A J, Manns M P. The validity and importance of subtypes in autoimmune hepatitis: a point of view.  Am J Gastroenterol . 1995;  90 1206-1211
    PubMedGoogle Scholar
  • 64 Czaja A J, Carpenter H A, Santrach P J. Significance of HLA DR4 in type 1 autoimmune hepatitis.  Gastroenterology . 1993;  105 1502-1507
    PubMedGoogle Scholar