Autoimmune hepatitis in humans

  • Stefan Lüth
  • Ansgar W. Lohse
Part of the Birkhäuser Advances in Infectious Diseases book series (BAID)


Autoimmune hepatitis (AIH) can occur in all age groups from earliest childhood up until the 8th decade. AIH affects women more commonly than men (3:1). Clinical presentation may be an acute hepatitis up to fulminant liver failure, but can also be asymptomatic.

AIH is characterised by lympho-plasmacellular infiltrates on liver biopsy, elevated liver enzymes in serum and association with the HLA haplotypes B8, DR3 and DR4 in the absence of active viral markers. Patients characteristically present with hypergammaglobulinemia, elevated serum levels of IgG and autoantibodies, such as antinuclear antibodies (ANA), smooth muscle antibodies (SMA), antibodies to soluble liver antigen/ liver pancreas (SLA/LP) or to liver-kidney microsomes (LKM).

Corticosteroids are the drug of choice for remission induction, azathioprine the drug of choice for maintenance of remission. The rapid response to immunosuppressive treatment supports the diagnosis of AIH and leads to a good long-term prognosis. Treatment duration remains controversial and can be discussed after resolution of all clinical, laboratory and histological manifestations of disease activity. Treatment should be maintained for a minimum of 3 years.


Primary Biliary Cirrhosis Primary SCLEROSING Cholangitis Autoimmune Hepatitis MYCOPHENOLATE MOFETIL Fulminant Liver Failure 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Mackay IR, Weiden S, Ungar B (1964) Treatment of active chronic hepatitis and lupoid hepatitis with 6-Mercaptopurine and Azathioprine. Lancet 42: 899–902CrossRefGoogle Scholar
  2. 2.
    O’Brien EN, Goble AJ, Mackay IR (1958) Plasma-transaminase activity as an index of the effectiveness of cortisone in chronic hepatitis. Lancet 1: 1245–1249PubMedCrossRefGoogle Scholar
  3. 3.
    Krawitt EL (2006) Autoimmune Hepatitis. N Engl J Med 354: 54–66PubMedCrossRefGoogle Scholar
  4. 4.
    Kammer AR, van der Burg SH, Grabscheid B, Hunziker IP, Kwappenberg KM, Reichen J, Melief CJ, Cerny A (1999) Molecular mimicry of human cytochrome P450 by hepatitis C virus at the level of cytotoxic T cell recognition. J Exp Med 190: 169–176PubMedCrossRefGoogle Scholar
  5. 5.
    Miyakawa H, Kitazawa E, Kikchi K, Fujikawa H, Kawaguchi N, Abe K, Matsushita H, Igarashi T, Hankins RW, Kako M (2001) Immunoreactivity to various human cytochrome P450 proteins of sera from patients with autoimmune hepatitis, chronic hepatitis B and chronic hepatitis C. Autoimmunity 33: 23–32CrossRefGoogle Scholar
  6. 6.
    Corchero J, Granvil CP, Akiyama TE, Hayhurst GP, Pimprale S, Feigenbaum L, Idie JR, Gonzalez FJ (2001) The CYP2D6 humanized mouse: effect of the human CYP2D6 transgene and HNF4 alpha on the disposition of debrisoquine in the mouse. Mol Pharmacol 60: 1260–1267PubMedGoogle Scholar
  7. 7.
    Holdener M, Hintermann H, Rhode A, Wolfe T, Gonzalez FJ, Johnson EF, Manns M, von Herrath MG, Christen U. A novel model for human autoimmune hepatitis: Breaking tolerance to human CYP2D6 by viral infection. Submitted for publication Google Scholar
  8. 8.
    Ando K, Guidotti LG, Wirth S, Ishikawa T, Missale G, Moriyama T, Schreiber RD, Schlicht HJ, Huang SN, Chisari FV (1994) Class I restricted cytotoxic T lymphocytes are directly cytopathic for their target cells in vivo. J Immunol 152: 3245–3253PubMedGoogle Scholar
  9. 9.
    Sacher T, Knolle P, Nichterlein T, Arnold B, Hammerling GJ, Limmer A (2002) CpG-ODN induced inflammation is sufficient to cause T-cell mediated autoaggression against hepatocytes. Eur J Immunol 32: 3628–3637PubMedCrossRefGoogle Scholar
  10. 10.
    Djilali-Saiah, Lapierre P, Vitozzi S, Alvarez F (2002) DNA vaccination breaks tolerance for a neo-self antigen in liver: a transgenic murine model of autoimmune hepatitis. J Immunol 169: 4889–4896PubMedGoogle Scholar
  11. 11.
    De Biasio MB, Periolo N, Avagnina A, Garcia de Davila MT, Ciacca M, Goni J, de Matteo E, Galoppo C, Canero-Velasco MC, Fainboim H et al (2006) Liver infiltrating mononuclear cells in children with type I autoimmune hepatitis. J Clin Pathol 59: 417–423PubMedCrossRefGoogle Scholar
  12. 12.
    Kurokohchi K, Arima K, Masaki T, Deguchi A, Nakai S, Morishita A, Yoneyama H, Ohgi T, Ono M, Yoshitake A et al (2006) Analysis of CD28 and bcl-2 expression on peripheral blood and liver-infiltrating mononuclear cells in patients with autoimmune hepatitis. J Clin Immunol 26: 323–330PubMedCrossRefGoogle Scholar
  13. 13.
    Kurokohchi K, Masaki T, Himoto T, Deguchi A, Nakai S, Morishita A, Yoneyama H, Kimura Y, Watanabe S, Kuriyama S (2006) Usefulness of liver infiltrating CD86-positive mononuclear cells for diagnosis of autoimmune hepatitis. World J Gastroenterol 12: 25230–25239Google Scholar
  14. 14.
    Longhi MS, Hussain MJ, Mitri RR, Arora SK, Mieli-Vergani G, Vergani D, Ma Y (2006) Functional study of CD4+CD25+ regulatory T cells in health and autoimmune hepatitis. J Immunol 176: 4484–4491PubMedGoogle Scholar
  15. 15.
    Alla V, Abraham J, Siddiqui J, Raina D, Wu GY, Chalasani NP and Bonkovsky HL (2006) Autoimmune hepatitis triggered by statins. J Clin Gastroenterol 40: 757–761Google Scholar
  16. 16.
    Czaja AJ, Freese DK (2002) Diagnosis and treatment of autoimmune hepatitis. Hepatology 36: 479–497PubMedCrossRefGoogle Scholar
  17. 17.
    Al-Chalabi T, Boccato S, Portmann BC, Mc Farlane IG, Heneghan MA (2006) Autoimmune hepatitis in the elderly: a systematic analysis of a large group of consecutive patients with definite AIH followed at a tertiary referral centre. J Hepatol 45: 575–583PubMedCrossRefGoogle Scholar
  18. 18.
    Feld JJ, Dinh H, Arenovich T, Marcus VA, Wanless IR, Heathcote EJ (2005) Autoimmune hepatitis: effect of symptoms and cirrhosis on natural history and outcome. Hepatology 42: 53–62PubMedCrossRefGoogle Scholar
  19. 19.
    Kogan J, Safadi R, Ashur Y, Shouval D, Ilan Y (2002) Prognosis of symptomatic versus asymptomatic hepatitis. A study of 68 patients. J Clin Gastroenterol 35: 75–81PubMedCrossRefGoogle Scholar
  20. 20.
    Robert SK, Therneau T, Czaja AJ (1996) Prognosis of histological cirrhosis in type-1 autoimmune hepatitis. Gastroenterology 110: 848–857CrossRefGoogle Scholar
  21. 21.
    Miyake Y, Iwasaki Y, Terada R, Onishi T, Okamoto R, Sakai N, Sakaguchi K, Shiratori Y (2006) Clinical characteristics of fulminant-type autoimmune hepatitis: an analysis of eleven cases. Aliment Pharmacol Ther 23: 1347–1353PubMedCrossRefGoogle Scholar
  22. 22.
    Lis-Swiety A, Brzezinska-Weislo L, Pierzchala E, Wcislo-Dziadecka D (2006) Systemic sclerosis-polymyositis overlap syndrome accompanied by autoimmune hepatitis and sarcoidosis of mediastinal lymph nodes. J Eur Acad Dermatol Venerol 20: 107–108CrossRefGoogle Scholar
  23. 23.
    Luth S, Birklein F, Schramm C, Herkel J, Hennes E, Muller-Forell W, Galle PR, Lohse AW (2006) Multiplex neuritis in a patient with autoimmune hepatitis: a case report. World J Gastroenterol 12: 5396–5398PubMedGoogle Scholar
  24. 24.
    Oki K, Yamane K, Koide J, Koide J, Mandai K, Nakanishi S, Fujikawa R, Kohno N (2006) A case of polyglandular autoimmune syndrome type III complicated by autoimmune hepatitis. Endocr J 53: 705–709PubMedCrossRefGoogle Scholar
  25. 25.
    Montano-Loza A, Czaja AJ, Carpenter HA, Piette A, Murphy D, Shums Z, Burlingame R, Norman GL (2006) Frequency and significance of antibodies to cyclic citrullinated peptide in type I autoimmune hepatitis. Autoimmunity 39: 341–348PubMedCrossRefGoogle Scholar
  26. 26.
    Heneghan MA, McFarlane IG (2002) Current and novel immunosuppressive therapy for autoimmune hepatitis. Hepatology 35: 7–13PubMedCrossRefGoogle Scholar
  27. 27.
    Johnson PJ (1996) Immunosuppressive drug mechanisms. In: IG McFarlane, R Williams (eds) In: Molecular basis of autoimmune hepatitis. RG Landes, Austin, 177–191Google Scholar
  28. 28.
    Johnson PJ, McFarlane IG, Williams R (1995) Azathioprine for long term maintenance of remission in autoimmune hepatitis. N Engl J Med 333: 958–963PubMedCrossRefGoogle Scholar
  29. 29.
    Czaja AJ (2002) Treatment strategies in autoimmune hepatitis. Clin Liver Dis 6: 799–824PubMedCrossRefGoogle Scholar
  30. 30.
    Kanzler S, Löhr H, Gerken G, Galle PR, Lohse AW (2001) Long-term management and prognosis of autoimmune hepatitis (AIH): A single center experience. Z Gastroenterol 39: 339–348PubMedCrossRefGoogle Scholar
  31. 31.
    Kanzler S, Gerken G, Lohr H, Galle PR, Meyer zum Büschenfelde KH, Lohse AW (2001) Duration of immunosuppressive therapy in autoimmune hepatitis. J Hepatol 34: 354–355PubMedCrossRefGoogle Scholar
  32. 32.
    Gautam M, Cheruvattath R, Balan V (2006) Recurrence of autoimmune liver disease after liver transplantation: a systematic review. Liver Transpl 12: 1813–1824PubMedCrossRefGoogle Scholar
  33. 33.
    Chatur N, Ramji A, Bain VG, Ma MM, Marotta PJ, Ghent CN, Lilly LB, Heathcote EJ, Deschenes M, Lee SS et al (2005) Transplant immunosuppressive agents in non-transplant chronic autoimmune hepatitis: the Canadian association for the study of the liver (CASL) experience with mycophenolate mofetil and tacrolimus. Liver Int 25: 723–727PubMedCrossRefGoogle Scholar
  34. 34.
    Roberts SK, Therneau TM, Czaja AJ (1996) Prognosis of histological cirrhosis in type I autoimmune hepatitis. Gastroenterology 110: 848–857PubMedCrossRefGoogle Scholar
  35. 35.
    Gohlke F, Lohse AW, Dienes HP, Lohr H, Marker-Hermann E, Gerken G, Meyer zum Buschenfelde KH (1996) Evidence for an overlap syndrome of autoimmune hepatitis and primary sclerosing cholangitis. J Hepatol 24: 699–705PubMedCrossRefGoogle Scholar
  36. 36.
    Lohse AW, zum Buschenfelde KH, Franz B, Kanzler S, Gerken G, Dienes HP (1999) Characterization of the overlap syndrome of primary biliary cirrhosis (PBC) and autoimmune hepatitis: evidence for it being a hepatitic form of PBC in genetically susceptible individuals. Hepatology 29: 1078–1084PubMedCrossRefGoogle Scholar

Copyright information

© Birkhäuser Verlag Basel/Switzerland 2008

Authors and Affiliations

  • Stefan Lüth
    • 1
  • Ansgar W. Lohse
    • 1
  1. 1.Department of MedicineUniversity Medical Center Hamburg-EppendorfHamburgGermany

Personalised recommendations