Skip to main content
Log in

Performance Parameters of the Conventional Serological Markers for Autoimmune Hepatitis

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background

Autoimmune hepatitis is defined by a conventional battery of autoantibodies that may also be present in other liver diseases.

Aims

To define the performance parameters of the conventional autoantibodies for autoimmune hepatitis, determine the diagnostic implications of simultaneous autoantibody production, and assess the performances of serological assays based on indirect immunofluorescence and enzyme immunoassay.

Methods

In this study, 265 adults satisfying codified criteria for autoimmune hepatitis and 342 adults who satisfied conventional diagnostic criteria for another chronic liver disease were each assessed for the conventional autoantibodies.

Results

Antinuclear antibodies, smooth muscle antibodies, and antibodies to liver kidney type 1 had sensitivities of only 32, 16, and 1%, respectively, for the diagnosis of autoimmune hepatitis, and their diagnostic accuracy ranged from 56 to 61%. The combination of antinuclear antibodies and smooth muscle antibodies at presentation had superior sensitivity (43%), specificity (99%), positive (97%) and negative (69%) predictabilities, and diagnostic accuracy (74%) than each marker alone. The occurrence of multiple autoantibodies was lower in other chronic liver diseases than in autoimmune hepatitis (8% versus 51%, p < 0.000001). The enzyme immunoassay for antinuclear antibodies had an accuracy that was not discriminative for autoimmune hepatitis (p = 0.06).

Conclusions

Isolated autoantibodies have a low diagnostic accuracy for autoimmune hepatitis. Concurrent antinuclear antibodies and smooth muscle antibodies have superior performance parameters. The enzyme immunoassay for antinuclear antibodies performs less well than the assay based on indirect immunofluorescence.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Manns MP, Czaja AJ, Gorham JD, et al. Practice guidelines of the American Association for the Study of Liver Diseases. Diagnosis and management of autoimmune hepatitis. Hepatology. 2010;51:2193–2213.

    CAS  PubMed  Google Scholar 

  2. Lindor KD, Gershwin ME, Poupon R, et al. AASLD practice guidelines. Primary biliary cirrhosis. Hepatology. 2009;50:291–308.

    Article  PubMed  Google Scholar 

  3. Czaja AJ, Carpenter HA, Santrach PJ, Moore SB. Immunologic features and HLA associations in chronic viral hepatitis. Gastroenterology. 1995;108:157–164.

    Article  CAS  PubMed  Google Scholar 

  4. Laskin CA, Vidins E, Blendis LM, Soloninka CA. Autoantibodies in alcoholic liver disease. Am J Med. 1990;89:129–133.

    Article  CAS  PubMed  Google Scholar 

  5. Loria P, Lonardo A, Leonardi F, et al. Non-organ-specific autoantibodies in nonalcoholic fatty liver disease: prevalence and correlates. Dig Dis Sci. 2003;48:2173–2181.

    Article  PubMed  Google Scholar 

  6. Adams LA, Lindor KD, Angulo P. The prevalence of autoantibodies and autoimmune hepatitis in patients with nonalcoholic fatty liver disease. Am J Gastroenterol. 2004;99:1316–1320.

    Article  CAS  PubMed  Google Scholar 

  7. Cotler SJ, Kanji K, Keshavarzian A, Jensen DM, Jakate S. Prevalence and significance of autoantibodies in patients with non-alcoholic steatohepatitis. J Clin Gastroenterol. 2004;38:801–804.

    Article  PubMed  Google Scholar 

  8. Bernstein RM, Neuberger JM, Bunn CC, et al. Diversity of autoantibodies in primary biliary cirrhosis and chronic active hepatitis. Clin Exp Immunol. 1984;55:553–560.

    CAS  PubMed  Google Scholar 

  9. Boberg KM, Fausa O, Haaland T, et al. Features of autoimmune hepatitis in primary sclerosing cholangitis: an evaluation of 114 primary sclerosing cholangitis patients according to a scoring system for the diagnosis of autoimmune hepatitis. Hepatology. 1996;23:1369–1376.

    Article  CAS  PubMed  Google Scholar 

  10. Czaja AJ, Santrach PJ, Breanndan Moore S. Shared genetic risk factors in autoimmune liver disease. Dig Dis Sci. 2001;46:140–147.

    Article  CAS  PubMed  Google Scholar 

  11. Lunel F, Abuaf N, Frangeul L, et al. Liver/kidney microsome antibody type 1 and hepatitis C virus infection. Hepatology. 1992;16:630–636.

    Article  CAS  PubMed  Google Scholar 

  12. Abuaf N, Lunel F, Giral P, et al. Non-organ specific autoantibodies associated with chronic C virus hepatitis. J Hepatol. 1993;18:359–364.

    Article  CAS  PubMed  Google Scholar 

  13. Leung PS, Rossaro L, Davis PA, et al. Antimitochondrial antibodies in acute liver failure: implications for primary biliary cirrhosis. Hepatology. 2007;46:1436–1442.

    Article  CAS  PubMed  Google Scholar 

  14. O’Brien C, Joshi S, Feld JJ, et al. Long-term follow-up of antimitochondrial antibody-positive autoimmune hepatitis. Hepatology. 2008;48:550–556.

    Article  PubMed  Google Scholar 

  15. Montano-Loza AJ, Carpenter HA, Czaja AJ. Frequency, behavior, and prognostic implications of antimitochondrial antibodies in type 1 autoimmune hepatitis. J Clin Gastroenterol. 2008;42:1047–1053.

    Article  PubMed  Google Scholar 

  16. Czaja AJ. The variant forms of autoimmune hepatitis. Ann Intern Med. 1996;125:588–598.

    CAS  PubMed  Google Scholar 

  17. Czaja AJ. Frequency and nature of the variant syndromes of autoimmune liver disease. Hepatology. 1998;28:360–365.

    Article  CAS  PubMed  Google Scholar 

  18. Heathcote J. Variant syndromes of autoimmune hepatitis. Clin Liver Dis. 2002;6:669–684.

    Article  PubMed  Google Scholar 

  19. Czaja AJ. Variant forms of autoimmune hepatitis. Curr Gastroenterol Rep. 1999;1:63–70.

    Article  CAS  PubMed  Google Scholar 

  20. Ben-Ari Z, Czaja AJ. Autoimmune hepatitis and its variant syndromes. Gut. 2001;49:589–594.

    Article  CAS  PubMed  Google Scholar 

  21. Alvarez F, Berg PA, Bianchi FB, et al. International autoimmune hepatitis group report: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol. 1999;31:929–938.

    Article  CAS  PubMed  Google Scholar 

  22. Hennes EM, Zeniya M, Czaja AJ, et al. Simplified criteria for the diagnosis of autoimmune hepatitis. Hepatology. 2008;48:169–176.

    Article  PubMed  Google Scholar 

  23. Czaja AJ. Performance parameters of the diagnostic scoring systems for autoimmune hepatitis. Hepatology. 2008;48:1540–1548.

    Article  PubMed  Google Scholar 

  24. Muratori L, Cataleta M, Muratori P, Lenzi M, Bianchi FB. Liver/kidney microsomal antibody type 1 and liver cytosol antibody type 1 concentrations in type 2 autoimmune hepatitis. Gut. 1998;42:721–726.

    Article  CAS  PubMed  Google Scholar 

  25. Czaja AJ. Behavior and significance of autoantibodies in type 1 autoimmune hepatitis. J Hepatol. 1999;30:394–401.

    Article  CAS  PubMed  Google Scholar 

  26. Czaja AJ, Norman GL. Autoantibodies in the diagnosis and management of liver disease. J Clin Gastroenterol. 2003;37:315–329.

    Article  PubMed  Google Scholar 

  27. Czaja AJ. The role of autoantibodies as diagnostic markers of autoimmune hepatitis. Expert Rev Clin Immunol. 2006;2:33–48.

    Article  CAS  PubMed  Google Scholar 

  28. Czaja AJ, Manns MP, Homburger HA. Frequency and significance of antibodies to liver/kidney microsome type 1 in adults with chronic active hepatitis. Gastroenterology. 1992;103:1290–1295.

    CAS  PubMed  Google Scholar 

  29. Czaja AJ, Freese DK. Practice guidelines of the American Association for the Study of Liver Diseases. Diagnosis and treatment of autoimmune hepatitis. Hepatology. 2002;36:479–497.

    Article  PubMed  Google Scholar 

  30. Ghany MG, Strader DB, Thomas DL, Seeff LB. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology. 2009;49:1335–1374.

    Article  CAS  PubMed  Google Scholar 

  31. Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology. 2009;50:661–662.

    Article  PubMed  Google Scholar 

  32. Czaja AJ, Carpenter HA. Sensitivity, specificity, and predictability of biopsy interpretations in chronic hepatitis. Gastroenterology. 1993;105:1824–1832.

    CAS  PubMed  Google Scholar 

  33. Chapman R, Fevery J, Kalloo A, et al. Diagnosis and management of primary sclerosing cholangitis. Hepatology. 2010;51:660–678.

    CAS  PubMed  Google Scholar 

  34. Ali R, Cusi K. New diagnostic and treatment approaches in non-alcoholic fatty liver disease (NAFLD). Ann Med. 2009;41:265–278.

    Article  CAS  PubMed  Google Scholar 

  35. Czaja AJ, Carpenter HA, Santrach PJ, Moore SB. Host- and disease-specific factors affecting steatosis in chronic hepatitis C. J Hepatol. 1998;29:198–206.

    Article  CAS  PubMed  Google Scholar 

  36. O’Shea RS, Dasarathy S, McCullough AJ. Alcoholic liver disease. Hepatology. 2010;51:307–328.

    PubMed  Google Scholar 

  37. Czaja AJ, Homburger HA. Autoantibodies in liver disease. Gastroenterology. 2001;120:239–249.

    Article  CAS  PubMed  Google Scholar 

  38. Czaja AJ, Cassani F, Cataleta M, Valentini P, Bianchi FB. Antinuclear antibodies and patterns of nuclear immunofluorescence in type 1 autoimmune hepatitis. Dig Dis Sci. 1997;42:1688–1696.

    Article  CAS  PubMed  Google Scholar 

  39. Homburger HA, Cahen YD, Griffiths J, Jacob GL. Detection of antinuclear antibodies: comparative evaluation of enzyme immunoassay and indirect immunofluorescence methods. Arch Pathol Lab Med. 1998;122:993–999.

    CAS  PubMed  Google Scholar 

  40. Czaja AJ, Manns MP. The validity and importance of subtypes in autoimmune hepatitis: a point of view. Am J Gastroenterol. 1995;90:1206–1211.

    CAS  PubMed  Google Scholar 

  41. Homberg JC, 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;7:1333–1339.

    Article  CAS  PubMed  Google Scholar 

  42. Manns MP, Griffin KJ, Sullivan KF, Johnson EF. LKM-1 autoantibodies recognize a short linear sequence in P450IID6, a cytochrome P-450 monooxygenase. J Clin Invest. 1991;88:1370–1378.

    Article  CAS  PubMed  Google Scholar 

  43. Czaja AJ, Carpenter HA, Manns MP. Antibodies to soluble liver antigen, P450IID6, and mitochondrial complexes in chronic hepatitis. Gastroenterology. 1993;105:1522–1528.

    CAS  PubMed  Google Scholar 

  44. Mishima S, Omagari K, Ohba K, et al. Clinical implications of antimitochondrial antibodies in type 1 autoimmune hepatitis: a longitudinal study. Hepatogastroenterology. 2008;55:221–227.

    CAS  PubMed  Google Scholar 

  45. Nezu S, Tanaka A, Yasui H, et al. Presence of antimitochondrial autoantibodies in patients with autoimmune hepatitis. J Gastroenterol Hepatol. 2006;21:1448–1454.

    CAS  PubMed  Google Scholar 

  46. Miyakawa H, Kikuchi K, Jong-Hon K, et al. High sensitivity of a novel ELISA for anti-M2 in primary biliary cirrhosis. J Gastroenterol. 2001;36:33–38.

    Article  CAS  PubMed  Google Scholar 

  47. Dahnrich C, Pares A, Caballeria L, et al. New ELISA for detecting primary biliary cirrhosis-specific antimitochondrial antibodies. Clin Chem. 2009;55:978–985.

    Article  PubMed  Google Scholar 

  48. Liu H, Norman GL, Shums Z, et al. PBC screen: an IgG/IgA dual isotype ELISA detecting multiple mitochondrial and nuclear autoantibodies specific for primary biliary cirrhosis. J Autoimmun. 2010;(Epub ahead of print).

  49. Courvalin JC, Worman HJ. Nuclear envelope protein autoantibodies in primary biliary cirrhosis. Semin Liver Dis. 1997;17:79–90.

    Article  CAS  PubMed  Google Scholar 

  50. Gao L, Tian X, Liu B, Zhang F. The value of antinuclear antibodies in primary biliary cirrhosis. Clin Exp Med. 2008;8:9–15.

    Article  CAS  PubMed  Google Scholar 

  51. Czaja AJ. Autoantibodies as prognostic markers in autoimmune liver disease. Dig Dis Sci. 2010;55:2144–2161.

    Article  CAS  PubMed  Google Scholar 

  52. Czaja AJ. Clinical features, differential diagnosis and treatment of autoimmune hepatitis in the elderly. Drugs Aging. 2008;25:219–239.

    Article  CAS  PubMed  Google Scholar 

  53. Czaja AJ, Donaldson PT. Gender effects and synergisms with histocompatibility leukocyte antigens in type 1 autoimmune hepatitis. Am J Gastroenterol. 2002;97:2051–2057.

    Article  CAS  PubMed  Google Scholar 

  54. Czaja AJ, dos Santos RM, Porto A, Santrach PJ, Moore SB. Immune phenotype of chronic liver disease. Dig Dis Sci. 1998;43:2149–2155.

    Article  CAS  PubMed  Google Scholar 

  55. Czaja AJ, Manns MP. Advances in the diagnosis, pathogenesis and management of autoimmune hepatitis. Gastroenterology. 2010;139:58–72.

    Article  CAS  PubMed  Google Scholar 

  56. Czaja AJ, Nishioka M, Morshed SA, Hachiya T. Patterns of nuclear immunofluorescence and reactivities to recombinant nuclear antigens in autoimmune hepatitis. Gastroenterology. 1994;107:200–207.

    CAS  PubMed  Google Scholar 

  57. Vergani D, Alvarez F, Bianchi FB, et al. Liver autoimmune serology: a consensus statement from the committee for autoimmune serology of the international autoimmune hepatitis group. J Hepatol. 2004;41:677–683.

    Article  PubMed  Google Scholar 

Download references

Conflict of interest

This work did not receive financial support from a funding agency or institution, and Albert J. Czaja, MD has no conflict of interests to declare.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Albert J. Czaja.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Czaja, A.J. Performance Parameters of the Conventional Serological Markers for Autoimmune Hepatitis. Dig Dis Sci 56, 545–554 (2011). https://doi.org/10.1007/s10620-010-1501-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-010-1501-1

Keywords

Navigation