Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Autoimmune hepatitis: Clinical manifestations and diagnosis

Michael A Heneghan, MD, MMedSc, FRCPI
Section Editor
Sanjiv Chopra, MD, MACP
Deputy Editor
Kristen M Robson, MD, MBA, FACG


Autoimmune hepatitis is a chronic hepatitis that occurs in children and adults of all ages. It is characterized by immunologic and autoimmunologic features, generally including the presence of circulating autoantibodies and high serum globulin concentrations [1]. Since it was first described in the 1950s, the disorder has been known by a variety of terms, including active chronic hepatitis, chronic active hepatitis, chronic aggressive hepatitis, lupoid hepatitis, plasma cell hepatitis, and, most commonly, autoimmune chronic active hepatitis. In 1992, the International Autoimmune Hepatitis Group recommended autoimmune hepatitis as the most appropriate and least redundant term for this disease [2].

Type 1 autoimmune hepatitis – Type 1, or classic autoimmune hepatitis, is characterized by circulating antibodies to nuclei (ANA) and/or smooth muscle (ASMA); the latter are thought to be reflective of more specific antiactin antibodies (AAA). AAA is not generally measured in most clinical laboratories, but ASMA with titers of 1:320 or greater generally reflect the presence of AAA. An ELISA technique for detecting antiactin antibodies (IgG anti F-actin) is available in some laboratories and is being used more frequently in commercial laboratories in North America. Other autoantibodies can occur in conjunction with or independent of ANA and ASMA. (See 'Autoantibodies' below and "Autoimmune hepatitis: Serologic markers".)

Type 2 autoimmune hepatitis – Type 2 autoimmune hepatitis is defined by the presence of antibodies to liver/kidney microsomes (ALKM-1) and/or to a liver cytosol antigen (ALC-1) (table 1).

The clinical manifestations of autoimmune hepatitis will be reviewed here. The treatment of this disorder is discussed separately. (See "Autoimmune hepatitis: Treatment".)


Autoimmune hepatitis is seen in all ethnic groups and can occur at any age, though it is often diagnosed in patients in their 40s or 50s [3-5]. It is more common in women than in men (female to male ratio of 3.6 to 1). In studies from Europe, the incidence is 0.9 to 2 per 100,000 population per year, with a prevalence of 11 to 25 per 100,000 population [4-8].

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Feb 21, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Krawitt EL. Autoimmune hepatitis. N Engl J Med 2006; 354:54.
  2. Johnson PJ, McFarlane IG. Meeting report: International Autoimmune Hepatitis Group. Hepatology 1993; 18:998.
  3. Manns MP, Czaja AJ, Gorham JD, et al. Diagnosis and management of autoimmune hepatitis. Hepatology 2010; 51:2193.
  4. Boberg KM, Aadland E, Jahnsen J, et al. Incidence and prevalence of primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis in a Norwegian population. Scand J Gastroenterol 1998; 33:99.
  5. Werner M, Prytz H, Ohlsson B, et al. Epidemiology and the initial presentation of autoimmune hepatitis in Sweden: a nationwide study. Scand J Gastroenterol 2008; 43:1232.
  6. Ngu JH, Bechly K, Chapman BA, et al. Population-based epidemiology study of autoimmune hepatitis: a disease of older women? J Gastroenterol Hepatol 2010; 25:1681.
  7. Primo J, Maroto N, Martínez M, et al. Incidence of adult form of autoimmune hepatitis in Valencia (Spain). Acta Gastroenterol Belg 2009; 72:402.
  8. Grønbæk L, Vilstrup H, Jepsen P. Autoimmune hepatitis in Denmark: incidence, prevalence, prognosis, and causes of death. A nationwide registry-based cohort study. J Hepatol 2014; 60:612.
  9. Muratori P, Granito A, Quarneti C, et al. Autoimmune hepatitis in Italy: the Bologna experience. J Hepatol 2009; 50:1210.
  10. Kessler WR, Cummings OW, Eckert G, et al. Fulminant hepatic failure as the initial presentation of acute autoimmune hepatitis. Clin Gastroenterol Hepatol 2004; 2:625.
  11. Bower WA, Johns M, Margolis HS, et al. Population-based surveillance for acute liver failure. Am J Gastroenterol 2007; 102:2459.
  12. Abe M, Onji M, Kawai-Ninomiya K, et al. Clinicopathologic features of the severe form of acute type 1 autoimmune hepatitis. Clin Gastroenterol Hepatol 2007; 5:255.
  13. Stravitz RT, Lefkowitch JH, Fontana RJ, et al. Autoimmune acute liver failure: proposed clinical and histological criteria. Hepatology 2011; 53:517.
  14. Floreani A, Niro G, Rosa Rizzotto E, et al. Type I autoimmune hepatitis: clinical course and outcome in an Italian multicentre study. Aliment Pharmacol Ther 2006; 24:1051.
  15. Yeoman AD, Al-Chalabi T, Karani JB, et al. Evaluation of risk factors in the development of hepatocellular carcinoma in autoimmune hepatitis: Implications for follow-up and screening. Hepatology 2008; 48:863.
  16. Hino-Arinaga T, Ide T, Kuromatsu R, et al. Risk factors for hepatocellular carcinoma in Japanese patients with autoimmune hepatitis type 1. J Gastroenterol 2012; 47:569.
  17. Ngu JH, Gearry RB, Frampton CM, Stedman CA. Mortality and the risk of malignancy in autoimmune liver diseases: a population-based study in Canterbury, New Zealand. Hepatology 2012; 55:522.
  18. Leung J, Dowling L, Obadan I, et al. Risk of non-melanoma skin cancer in autoimmune hepatitis. Dig Dis Sci 2010; 55:3218.
  19. Björnsson E, Talwalkar J, Treeprasertsuk S, et al. Patients with typical laboratory features of autoimmune hepatitis rarely need a liver biopsy for diagnosis. Clin Gastroenterol Hepatol 2011; 9:57.
  20. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Autoimmune hepatitis. J Hepatol 2015; 63:971.
  21. Hofer H, Oesterreicher C, Wrba F, et al. Centrilobular necrosis in autoimmune hepatitis: a histological feature associated with acute clinical presentation. J Clin Pathol 2006; 59:246.
  22. O'Brien C, Joshi S, Feld JJ, et al. Long-term follow-up of antimitochondrial antibody-positive autoimmune hepatitis. Hepatology 2008; 48:550.
  23. Frenzel C, Herkel J, Lüth S, et al. Evaluation of F-actin ELISA for the diagnosis of autoimmune hepatitis. Am J Gastroenterol 2006; 101:2731.
  24. Hennes EM, Zeniya M, Czaja AJ, et al. Simplified criteria for the diagnosis of autoimmune hepatitis. Hepatology 2008; 48:169.
  25. Wies I, Brunner S, Henninger J, et al. Identification of target antigen for SLA/LP autoantibodies in autoimmune hepatitis. Lancet 2000; 355:1510.
  26. Kernebeck T, Lohse AW, Grötzinger J. A bioinformatical approach suggests the function of the autoimmune hepatitis target antigen soluble liver antigen/liver pancreas. Hepatology 2001; 34:230.
  27. Herkel J, Heidrich B, Nieraad N, et al. Fine specificity of autoantibodies to soluble liver antigen and liver/pancreas. Hepatology 2002; 35:403.
  28. Czaja AJ, Morshed SA, Parveen S, Nishioka M. Antibodies to single-stranded and double-stranded DNA in antinuclear antibody-positive type 1-autoimmune hepatitis. Hepatology 1997; 26:567.
  29. Bridoux-Henno L, Maggiore G, Johanet C, et al. Features and outcome of autoimmune hepatitis type 2 presenting with isolated positivity for anti-liver cytosol antibody. Clin Gastroenterol Hepatol 2004; 2:825.
  30. Alvarez F, Berg PA, Bianchi FB, et al. International Autoimmune Hepatitis Group Report: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol 1999; 31:929.
  31. Yeoman AD, Westbrook RH, Al-Chalabi T, et al. Diagnostic value and utility of the simplified International Autoimmune Hepatitis Group (IAIHG) criteria in acute and chronic liver disease. Hepatology 2009; 50:538.
  32. Czaja AJ. Comparability of probable and definite autoimmune hepatitis by international diagnostic scoring criteria. Gastroenterology 2011; 140:1472.
  33. Rust C, Beuers U. Overlap syndromes among autoimmune liver diseases. World J Gastroenterol 2008; 14:3368.
  34. Mehendiratta V, Mitroo P, Bombonati A, et al. Serologic markers do not predict histologic severity or response to treatment in patients with autoimmune hepatitis. Clin Gastroenterol Hepatol 2009; 7:98.
  35. Dinani AM, Fischer SE, Mosko J, et al. Patients with autoimmune hepatitis who have antimitochondrial antibodies need long-term follow-up to detect late development of primary biliary cirrhosis. Clin Gastroenterol Hepatol 2012; 10:682.
  36. Leung PS, Rossaro L, Davis PA, et al. Antimitochondrial antibodies in acute liver failure: implications for primary biliary cirrhosis. Hepatology 2007; 46:1436.
  37. Bernal W, Ma Y, Smith HM, et al. The significance of autoantibodies and immunoglobulins in acute liver failure: a cohort study. J Hepatol 2007; 47:664.
  38. Bellary S, Schiano T, Hartman G, Black M. Chronic hepatitis with combined features of autoimmune chronic hepatitis and chronic hepatitis C: favorable response to prednisone and azathioprine. Ann Intern Med 1995; 123:32.
  39. Bianchi FB. Autoimmune hepatitis: the lesson of the discovery of hepatitis C virus. J Hepatol 1993; 18:273.
  40. Yatsuji S, Hashimoto E, Kaneda H, et al. Diagnosing autoimmune hepatitis in nonalcoholic fatty liver disease: is the International Autoimmune Hepatitis Group scoring system useful? J Gastroenterol 2005; 40:1130.
  41. Suzuki A, Brunt EM, Kleiner DE, et al. The use of liver biopsy evaluation in discrimination of idiopathic autoimmune hepatitis versus drug-induced liver injury. Hepatology 2011; 54:931.