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18 - Autoimmune Hepatitis

from SECTION III - HEPATITIS AND IMMUNE DISORDERS

Published online by Cambridge University Press:  18 December 2009

By
Giorgina Mieli-Vergani M.D., Ph.D.  and
Diego Vergani M.D., Ph.D.
Edited by
Frederick J. Suchy ,
Ronald J. Sokol  and
William F. Balistreri
Giorgina Mieli-Vergani M.D., Ph.D.
Affiliation:
Alex Mowat Professor of Paediatric Hepatology, Department of Liver Studies and Transplantation, King's College London School of Medicine at King's College Hospital, London, England; Director of the Paediatric Liver Centre, Department of Children's Health, King's College Hospital, London, England
Diego Vergani M.D., Ph.D.
Affiliation:
Professor of Liver Immunopathology, Department of Liver Studies and Transplantation, King's College London School of Medicine at King's College Hospital, London, England
Frederick J. Suchy
Affiliation:
Mount Sinai School of Medicine, New York
Ronald J. Sokol
Affiliation:
University of Colorado, Denver
William F. Balistreri
Affiliation:
University of Cincinnati
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Summary

Autoimmune hepatitis (AIH) is a progressive inflammatory liver disorder preferentially affecting females and characterized serologically by high aminotransferase levels, elevated immunoglobulin G (IgG), and presence of autoantibodies and histologically by interface hepatitis in the absence of a known etiology. AIH is divided into two types according to the auto-antibody profile: patients with type 1 are positive for antinuclear antibody (ANA) and/or anti–smooth muscle antibody (ASMA); patients with type 2 are positive for anti–liver-kidney-microsomal antibody type 1 (anti-LKM-1). AIH responds satisfactorily to immunosuppressive treatment.

HISTORY AND EPIDEMIOLOGY

Autoimmune hepatitis is a relatively recently recognized disease, having been first described by Waldenström [1] in 1950. Seropositivity for ANA, the hallmark of systemic lupus erythematosus, led Mackay et al. [2] to call it lupoid hepatitis, a term no longer used. Because the disease frequently presents acutely, similarly obsolete is the term chronic active hepatitis, which implied that the disease should be chronic, that is, of at least 6 months' duration, before institution of immunosuppression. Before the efficacy of immunosuppression was established, untreated severe AIH had a mortality rate of 50% at 5 years and 90% at 10 years [3, 4]. The prevalence of AIH is unknown. Studies in adults have reported rates varying from 1 in 200,000 in the U.S. general population [5] to 20 in 100,000 in females over 14 years of age in Spain [6]; both figures are probably underestimates.

Type
Chapter
Information
Liver Disease in Children , pp. 447 - 458
Publisher: Cambridge University Press
Print publication year: 2007

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References

Waldenström, J. Leber, Blutproteine und Nahrungseiweiss. Dtsch Z Verdau Staffwechselkr 1950;15:113–19.Google Scholar
Mackay, I R, Taft, L I, Cowling, DC.Lupoid hepatitis. Lancet 1956;271:1323–6.CrossRefGoogle Scholar
Soloway, R D, Summerskill, W H, Baggenstoss, A H. Clinical, biochemical, and histological remission of severe chronic active liver disease: a controlled study of treatments and early prognosis. Gastroenterology 1972;63:820–33.Google ScholarPubMed
Cook, G C, Mulligan, R, Sherlock, S.Controlled prospective trial of corticosteroid therapy in active chronic hepatitis. Q J Med 1971;40:159–85.CrossRefGoogle ScholarPubMed
Manns, M PLuttig, BObermayer-Straub, P. Autoimmune hepatitis. In: Rose, N RMackay, I R. The autoimmune diseases. 3rd ed. San Diego: Academic Press, 1998:511–25.Google Scholar
Primo, J, Merino, C, Fernandez, J. Incidence and prevalence of autoimmune hepatitis in the area of the Hospital de Sagunto (Spain). Gastroenterol Hepatol 2004;27:239–43.CrossRefGoogle Scholar
Gregorio, G V, Portmann, B, Reid, F. Autoimmune hepatitis in childhood: a 20-year experience. Hepatology 1997;25:541–7.CrossRefGoogle ScholarPubMed
Krawitt, EL.Autoimmune hepatitis: classification, heterogeneity, and treatment. Am J Med 1994;96:23S–26S.CrossRefGoogle ScholarPubMed
Manns, M P, Vogel, A.Autoimmune hepatitis, from mechanisms to therapy. Hepatology 2006;43:S132–44.CrossRefGoogle Scholar
Ahonen, P, Myllarniemi, S, Sipila, I, Perheentupa, J.Clinical variation of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) in a series of 68 patients. N Engl J Med 1990;322:1829–36.CrossRefGoogle Scholar
Johnson, P J, McFarlane, IG.Meeting report: International Autoimmune Hepatitis Group. Hepatology 1993;18:998–1005.CrossRefGoogle ScholarPubMed
Alvarez, F, Berg, P A, Bianchi, F B. International Autoimmune Hepatitis Group Report: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol 1999;31:929–38.CrossRefGoogle ScholarPubMed
Jablonska, S, Chorzelski, T, Zalewski, T, Blaszczyk, M.[Autoimmune (“lupoid”) hepatitis in the light of immunofluorescence studies]. Dermatol Monatsschr 1972;158:271–7.Google Scholar
Vergani, D, Alvarez, F, Bianchi, F B. Liver autoimmune serology: a consensus statement from the committee for autoimmune serology of the International Autoimmune Hepatitis Group. J Hepatol 2004;41:677–83.CrossRefGoogle Scholar
Bottazzo, G F, Florin-Christensen, A, Fairfax, A. Classification of smooth muscle autoantibodies detected by immunofluorescence. J Clin Pathol 1976;29:403–10.CrossRefGoogle ScholarPubMed
Muratori, P, Muratori, L, Agostinelli, D. Smooth muscle antibodies and type 1 autoimmune hepatitis. Autoimmunity 2002;35:497–500.CrossRefGoogle ScholarPubMed
Gregorio, G V, Portmann, B, Mowat, A P. A 12-year-old girl with antimitochondrial antibody-positive autoimmune hepatitis. J Hepatol 1997;27:751–4.CrossRefGoogle ScholarPubMed
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;116:643–9.CrossRefGoogle ScholarPubMed
Manns, M, Gerken, G, Kyriatsoulis, A. Characterisation of a new subgroup of autoimmune chronic active hepatitis by autoantibodies against a soluble liver antigen. Lancet 1987;1:292–4.CrossRefGoogle ScholarPubMed
Ma, Y, Bogdanos, B P, Williams, R. Anti-SLA antibody is a marker of severity of liver damage in patients with autoimmune liver disease. J Hepatol 2001;34:212.Google Scholar
Donaldson, PT.Genetics in autoimmune hepatitis. Semin Liver Dis 2002;22:353–64.CrossRefGoogle ScholarPubMed
Donaldson, PT.Genetics of autoimmune and viral liver diseases; understanding the issues. J Hepatol 2004;41:327–32.CrossRefGoogle ScholarPubMed
Ma, Y, Bogdanos, D P, Hussain, M J. Polyclonal T-cell responses to cytochrome P450IID6 are associated with disease activity in autoimmune hepatitis type-2. Gastroenterology 2006;130:868–82.CrossRefGoogle ScholarPubMed
Vergani, D, Wells, L, Larcher, V F. Genetically determined low C4: a predisposing factor to autoimmune chronic active hepatitis. Lancet 1985;2:294–8.CrossRefGoogle ScholarPubMed
Gregorio, G V, Portmann, B, Karani, J. Autoimmune hepatitis/sclerosing cholangitis overlap syndrome in childhood: a 16-year prospective study. Hepatology 2001;33:544–53.CrossRefGoogle ScholarPubMed
Gregorio, G V, Jones, H, Choudhuri, K. Autoantibody prevalence in chronic hepatitis B virus infection: effect in interferon alfa. Hepatology 1996;24:520–3.CrossRefGoogle ScholarPubMed
Gregorio, G V, Pensati, P, Iorio, R. Autoantibody prevalence in children with liver disease due to chronic hepatitis C virus (HCV) infection. Clin Exp Immunol 1998;112:471–6.CrossRefGoogle ScholarPubMed
Dhawan, A, Taylor, R M, Cheeseman, P. Wilson's disease in children: 37-year experience and revised King's score for liver transplantation. Liver Transpl 2005;11:441–8.CrossRefGoogle ScholarPubMed
Liston, A, Lesage, S, Gray, D H. Genetic lesions in T-cell tolerance and thresholds for autoimmunity. Immunol Rev 2005;204:87–101.CrossRefGoogle ScholarPubMed
Simmonds, M J, Gough, SC.Genetic insights into disease mechanisms of autoimmunity. Br Med Bull 2004;71:93–113.CrossRefGoogle ScholarPubMed
Fainboim, L, Canero Velasco, M C. Protracted, but not acute, hepatitis A virus infection is strongly associated with HLA-DRB*1301, a marker for pediatric autoimmune hepatitis. Hepatology 2001;33:1512–17.CrossRefGoogle Scholar
Pando, M, Larriba, J, Fernandez, G C. Pediatric and adult forms of type I autoimmune hepatitis in Argentina: evidence for differential genetic predisposition. Hepatology 1999;30:1374–80.CrossRefGoogle ScholarPubMed
Lankisch, T O, Strassburg, C P, Debray, D. Detection of autoimmune regulator gene mutations in children with type 2 autoimmune hepatitis and extrahepatic immune-mediated diseases. J Pediatr 2005;146:839–42.CrossRefGoogle ScholarPubMed
Senaldi, G, Portmann, B, Mowat, A P. Immunohistochemical features of the portal tract mononuclear cell infiltrate in chronic aggressive hepatitis. Arch Dis Child 1992;67:1447–53.CrossRefGoogle ScholarPubMed
Takeda, K, Hayakawa, Y, Kaer, L. Critical contribution of liver natural killer T cells to a murine model of hepatitis. Proc Natl Acad Sci U S A 2000;97:5498–503.CrossRefGoogle ScholarPubMed
Nouri-Aria, K T, Lobo-Yeo, A, Vergani, D. T suppressor cell function and number in children with liver disease. Clin Exp Immunol 1985;61:283–9.Google Scholar
Nouri-Aria, K T, Hegarty, J E, Alexander, G J. Effect of corticosteroids on suppressor-cell activity in “autoimmune” and viral chronic active hepatitis. N Engl J Med 1982;307:1301–4.CrossRefGoogle ScholarPubMed
Vento, S, Hegarty, J E, Bottazzo, G. Antigen specific suppressor cell function in autoimmune chronic active hepatitis. Lancet 1984;1:1200–4.CrossRefGoogle ScholarPubMed
Longhi, M S, Ma, Y, Bogdanos, D P. Impairment of CD4+ CD25+ regulatory T-cells in autoimmune liver disease. J Hepatol 2004;41:31–7.CrossRefGoogle ScholarPubMed
Shevach, EM.CD4+ CD25+ suppressor T cells: more questions than answers. Nat Rev Immunol 2002;2:389–400.CrossRefGoogle ScholarPubMed
Lobo-Yeo, A, Alviggi, L, Mieli-Vergani, G. Preferential activation of helper/inducer T lymphocytes in autoimmune chronic active hepatitis. Clin Exp Immunol 1987;67:95–104.Google ScholarPubMed
Wen, L, Peakman, M, Lobo-Yeo, A. T-cell-directed hepatocyte damage in autoimmune chronic active hepatitis. Lancet 1990;336:1527–30.CrossRefGoogle ScholarPubMed
Wen, L, Peakman, M, Mieli-Vergani, G, Vergani, D.Elevation of activated gamma delta T cell receptor bearing T lymphocytes in patients with autoimmune chronic liver disease. Clin Exp Immunol 1992;89:78–82.CrossRefGoogle ScholarPubMed
Wen, L, Ma, Y, Bogdanos, D P. Pediatric autoimmune liver diseases: the molecular basis of humoral and cellular immunity. Curr Mol Med 2001;1:379–89.CrossRefGoogle ScholarPubMed
Jaeckel, E.Animal models of autoimmune hepatitis. Semin Liver Dis 2002;22:325–38.CrossRefGoogle ScholarPubMed
Peters, MG.Animal models of autoimmune liver disease. Immunol Cell Biol 2002;80:113–16.CrossRefGoogle ScholarPubMed
Lohse, A W, Meyer zum Buschenfelde, KH.Remission of experimental autoimmune hepatitis is associated with antigen-specific and non-specific immunosuppression. Clin Exp Immunol 1993;94:163–7.CrossRefGoogle ScholarPubMed
Lohse, A W, Kogel, M, Meyer zum Buschenfelde, KH.Evidence for spontaneous immunosuppression in autoimmune hepatitis. Hepatology 1995;22:381–8.Google ScholarPubMed
Lapierre, P, Djilali-Saiah, I, Vitozzi, S, Alvarez, F.A murine model of type 2 autoimmune hepatitis: xenoimmunization with human antigens. Hepatology 2004;39:1066–74.CrossRefGoogle ScholarPubMed
Lapierre, P, Beland, K, Djilali-Saiah, I, Alvarez, F.Type 2 autoimmune hepatitis murine model: the influence of genetic background in disease development. J Autoimmun 2006;26:82–9.CrossRefGoogle ScholarPubMed
Christen, U, Rhode, A, Johnson,, E. Development of an animal model for autoimmune hepatitis: breaking of self-tolerance in the CYP2D6 humanized mouse by viral infection. Hepatology; 2003;162A.CrossRefGoogle Scholar
Mieli-Vergani, GVergani, D.Autoimmune hepatitis in children. Clin Liver Dis 2002;6:623–34.CrossRefGoogle ScholarPubMed
Rumbo, C, Emerick, K M, Emre, S, Shneider, BL.Azathioprine metabolite measurements in the treatment of autoimmune hepatitis in pediatric patients: a preliminary report. J Pediatr Gastroenterol Nutr 2002;35:391–8.CrossRefGoogle ScholarPubMed
Gregorio, G V, McFarlane, B, Bracken, P. Organ and non-organ specific autoantibody titres and IgG levels as markers of disease activity: a longitudinal study in childhood autoimmune liver disease. Autoimmunity 2002;35:515–19.CrossRefGoogle ScholarPubMed
Mieli-Vergani, GBargiota, KSamyn, MVergani, D. Therapeutic aspects of autoimmune liver disease in children. In: Dienes, H PLeuschner, ULohse, A WManns, M P. Autoimmune liver diseases – Falk Symposium. Dordrecht: Springer, 2005:278–82.Google Scholar
Johnson, P J, McFarlane, I G, Williams, R.Azathioprine for long-term maintenance of remission in autoimmune hepatitis. N Engl J Med 1995;333:958–63.CrossRefGoogle ScholarPubMed
Alvarez, F, Ciocca, M, Canero-Velasco, C. Short-term cyclosporine induces a remission of autoimmune hepatitis in children. J Hepatol 1999;30:222–7.CrossRefGoogle ScholarPubMed
Lindor, KD.Ursodiol for primary sclerosing cholangitis. Mayo Primary Sclerosing Cholangitis-Ursodeoxycholic Acid Study Group. N Engl J Med 1997;336:691–5.CrossRefGoogle ScholarPubMed
Mitchell, S A, Bansi, D S, Hunt, N. A preliminary trial of high-dose ursodeoxycholic acid in primary sclerosing cholangitis. Gastroenterology 2001;121:900–7.CrossRefGoogle ScholarPubMed
Vergani, D, Mieli-Vergani, G.Autoimmunity after liver transplantation. Hepatology 2002;36:271–6.CrossRefGoogle ScholarPubMed
Kerkar, N, Hadzic, N, Davies, E T. De-novo autoimmune hepatitis after liver transplantation. Lancet 1998;351:409–13.CrossRefGoogle ScholarPubMed
Mieli-Vergani, G, Vergani, D.De novo autoimmune hepatitis after liver transplantation. J Hepatol 2004;40:3–7.CrossRefGoogle ScholarPubMed
Vergani, D, Choudhuri, K, Bogdanos, D P, Mieli-Vergani, G.Pathogenesis of autoimmune hepatitis. Clin Liver Dis 2002;6:727–37.CrossRefGoogle ScholarPubMed
Aguilera, I, Sousa, J M, Gavilan, F. Glutathione S-transferase T1 mismatch constitutes a risk factor for de novo immune hepatitis after liver transplantation. Liver Transpl 2004;10:1166–72.CrossRefGoogle Scholar

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  • Autoimmune Hepatitis
    • By Giorgina Mieli-Vergani, M.D., Ph.D., Alex Mowat Professor of Paediatric Hepatology, Department of Liver Studies and Transplantation, King's College London School of Medicine at King's College Hospital, London, England; Director of the Paediatric Liver Centre, Department of Children's Health, King's College Hospital, London, England, Diego Vergani, M.D., Ph.D., Professor of Liver Immunopathology, Department of Liver Studies and Transplantation, King's College London School of Medicine at King's College Hospital, London, England
  • Edited by Frederick J. Suchy, Mount Sinai School of Medicine, New York, Ronald J. Sokol, University of Colorado, Denver, William F. Balistreri, University of Cincinnati
  • Book: Liver Disease in Children
  • Online publication: 18 December 2009
  • Chapter DOI: https://doi.org/10.1017/CBO9780511547409.020
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  • Autoimmune Hepatitis
    • By Giorgina Mieli-Vergani, M.D., Ph.D., Alex Mowat Professor of Paediatric Hepatology, Department of Liver Studies and Transplantation, King's College London School of Medicine at King's College Hospital, London, England; Director of the Paediatric Liver Centre, Department of Children's Health, King's College Hospital, London, England, Diego Vergani, M.D., Ph.D., Professor of Liver Immunopathology, Department of Liver Studies and Transplantation, King's College London School of Medicine at King's College Hospital, London, England
  • Edited by Frederick J. Suchy, Mount Sinai School of Medicine, New York, Ronald J. Sokol, University of Colorado, Denver, William F. Balistreri, University of Cincinnati
  • Book: Liver Disease in Children
  • Online publication: 18 December 2009
  • Chapter DOI: https://doi.org/10.1017/CBO9780511547409.020
Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

  • Autoimmune Hepatitis
    • By Giorgina Mieli-Vergani, M.D., Ph.D., Alex Mowat Professor of Paediatric Hepatology, Department of Liver Studies and Transplantation, King's College London School of Medicine at King's College Hospital, London, England; Director of the Paediatric Liver Centre, Department of Children's Health, King's College Hospital, London, England, Diego Vergani, M.D., Ph.D., Professor of Liver Immunopathology, Department of Liver Studies and Transplantation, King's College London School of Medicine at King's College Hospital, London, England
  • Edited by Frederick J. Suchy, Mount Sinai School of Medicine, New York, Ronald J. Sokol, University of Colorado, Denver, William F. Balistreri, University of Cincinnati
  • Book: Liver Disease in Children
  • Online publication: 18 December 2009
  • Chapter DOI: https://doi.org/10.1017/CBO9780511547409.020
Available formats
×