Digestive Diseases and Sciences

, Volume 55, Issue 8, pp 2417–2421 | Cite as

The Development of Autoimmune Hepatitis and Primary Biliary Cirrhosis Overlap Syndrome During the Course of Connective Tissue Diseases: Report of Three Cases and Review of the Literature

  • Cumali EfeEmail author
  • Ersan Ozaslan
  • Narin Nasiroglu
  • Hasan Tunca
  • Tugrul Purnak
  • Emin Altiparmak
Case Report


The term hepatic overlap syndrome is used to describe variant forms of autoimmune hepatitis (AIH) that present characteristics of AIH and primary biliary cirrhosis (PBS) or primary sclerosing cholangitis (PSC). It is still unclear whether these overlap syndromes are different entities or they are only variants of major autoimmune hepatopathies, and they do not have codified definitions [1, 2, 3]. Patients with overlap syndrome present with both cholestatic and hepatitic profiles, either simultaneously or consecutively. AIH–PBC is the most common form, affecting almost 10% of patients with AIH or PBC [2, 3, 4]. Liver involvement in patients with connective tissue diseases (CTD) is an uncommon condition. Hepatotoxic drugs, coincident viral hepatitis and development of autoimmune hepatic diseases have been implicated as the main causes of liver diseases in patients with connective tissue diseases [5, 6, 7]. We present here the development of AIH–PBC overlap syndrome in three...


Connective tissue disease Autoimmune hepatitis Primary biliary cirrhosis Overlap syndrome 


  1. 1.
    Beuers U. Hepatic overlap syndromes. J Hepatol. 2005;42:93–99.CrossRefGoogle Scholar
  2. 2.
    Rust C, Beuers U. Overlap syndromes among autoimmune liver diseases. World J Gastroenterol. 2008;14:3368–3373.CrossRefPubMedGoogle Scholar
  3. 3.
    Gheorghe L, Iacob S, Gheorghe C, et al. Frequency and predictive factors for overlap syndrome between autoimmune hepatitis and primary cholestatic liver disease. Eur J Gastroenterol Hepatol. 2004;16:585–592.CrossRefPubMedGoogle Scholar
  4. 4.
    Chazouillères O, Wendum D, Serfaty L, Rosmorduc O, Poupon R. Long term outcome and response to therapy of primary biliary cirrhosis-autoimmune hepatitis overlap syndrome. J Hepatol. 2006;44:400–406.CrossRefPubMedGoogle Scholar
  5. 5.
    Matsumoto T, Kobayashi S, Shimizu H, et al. The liver in connective diseases: pathologic study of 160 cases with particular reference to hepatic arteritis, primary biliary cirrhosis, autoimmune hepatitis and nodular regenerative hyperplasia of the liver. Liver. 2000;20:366–373.CrossRefPubMedGoogle Scholar
  6. 6.
    Youssef WI, Tavill AS. Connective tissue diseases and the liver. J Clin Gastroenterol. 2002;35:345–349.CrossRefPubMedGoogle Scholar
  7. 7.
    West M, Jasin HE, Medhekar S. The development of connective tissue diseases in patients with autoimmune hepatitis: a case series. Semin Arthritis Rheum. 2006;35:344–348.CrossRefPubMedGoogle Scholar
  8. 8.
    Anaya JM, Gómez L, Castiblanco J. Is there a common genetic basis for autoimmune diseases? Clin Dev Immunol. 2006;13:185–195.CrossRefPubMedGoogle Scholar
  9. 9.
    Fridkis-Hareli M. Immunogenetic mechanisms for the coexistence of organ-specific and systemic autoimmune diseases. J Autoimmune Dis. 2008;15:1–7.CrossRefGoogle Scholar
  10. 10.
    Amital H, Eric Gershwin M, Shoenfeld Y. Reshaping the mosaic of autoimmunity. Semin Arthritis Rheum. 2006;35:341–343.CrossRefPubMedGoogle Scholar
  11. 11.
    Turkcapar N, Olmez U, Ozer D, Duzgun N, Duman M. A case of overlap syndrome with rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis and secondary Sjögren’s syndrome. Rheumatol Int. 2006;26:841–845.CrossRefPubMedGoogle Scholar
  12. 12.
    Poupon R, Chazouilleres O, Corpechot C, Chrétien Y. Development of autoimmune hepatitis in patients with typical primary biliary cirrhosis. Hepatology. 2006;44:85–90.CrossRefPubMedGoogle Scholar
  13. 13.
    Lindgren S, Glaumann H, Almer S, et al. Transitions between variant forms of primary biliary cirrhosis during long-term follow-up. Eur J Intern Med. 2009;20:398–402.CrossRefPubMedGoogle Scholar
  14. 14.
    Hochberg MC. Updating the American college of rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40:1725.CrossRefPubMedGoogle Scholar
  15. 15.
    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.CrossRefPubMedGoogle Scholar
  16. 16.
    Chazouillères O, Wendum D, Serfaty L, Montembault S, Rosmorduc O, Poupon R. Primary biliary cirrhosis-autoimmune hepatitis overlap syndrome: clinical features and response to therapy. Hepatology. 1998;28:296–301.CrossRefPubMedGoogle Scholar
  17. 17.
    Tojo J, Ohira H, Abe K, et al. Autoimmune hepatitis accompanied by systemic lupus erythematosus. Intern Med. 2004;43:258–262.CrossRefPubMedGoogle Scholar
  18. 18.
    Abraham S, Begum S, Isenberg D. Hepatic manifestations of autoimmune rheumatic diseases. Ann Rheum Dis. 2004;63:123–129.CrossRefPubMedGoogle Scholar
  19. 19.
    Runyon BA, LaBrecque DR, Anuras S. The spectrum of liver disease in systemic lupus erythematosus. Report of 33 histologically-proved cases and review of the literature. Am J Med. 1980;69:187–194.CrossRefPubMedGoogle Scholar
  20. 20.
    Matsumoto T, Yoshimine T, Shimouchi K, et al. The liver in systemic lupus erythematosus: pathologic analysis of 52 cases and review of Japanese autopsy registry data. Hum Pathol. 1992;23:1151–1158.CrossRefPubMedGoogle Scholar
  21. 21.
    Leggett BA. The liver in systemic lupus erythematosus. J Gastroenterol Hepatol. 1993;8:84–88.CrossRefPubMedGoogle Scholar
  22. 22.
    Hall S, Czaja AJ, Kaufman DK, Markowitz H, Ginsburg WW. How lupoid is lupoid hepatitis? J Rheumatol. 1986;13:95–98.PubMedGoogle Scholar
  23. 23.
    Culp KS, Fleming CR, Duffy J, Baldus WP, Dickson ER. Autoimmune associations in primary biliary cirrhosis. Mayo Clin Proc. 1982;57:365–370.PubMedGoogle Scholar
  24. 24.
    Doniach D, Walker G. Mitochondrial antibodies (AMA). Gut. 1974;15:664–668.CrossRefPubMedGoogle Scholar
  25. 25.
    Heyman SN, Spectre G, Aamar S, Rubinger D, Pappo O, Ackerman Z. Autoimmune cholangiopathy associated with systemic lupus erythematosus. Liver. 2002;22:102–106.CrossRefPubMedGoogle Scholar
  26. 26.
    Marie I, Levesque H, Tranvouez JL, et al. Autoimmune hepatitis and systemic sclerosis: a new overlap syndrome? Rheumatology (Oxford). 2001;40:102–106.CrossRefGoogle Scholar
  27. 27.
    Lock G, Holstege A, Lang B, Schölmerich J. Gastrointestinal manifestations of progressive systemic sclerosis. Am J Gastroenterol. 1997;92:763–771.PubMedGoogle Scholar
  28. 28.
    Bartholomew LG, Caın JC, Winkelmann RK, Baggenstoss AH. Chronic disease of the liver associated with systemic scleroderma. Am J Dig Dis. 1964;9:43–55.CrossRefPubMedGoogle Scholar
  29. 29.
    D’Angelo WA, Fries JF, Masi AT, Shulman LE. Pathologic observations in systemic sclerosis (scleroderma). A study of fifty-eight autopsy cases and fifty-eight matched controls. Am J Med. 1969;46:428–440.CrossRefPubMedGoogle Scholar
  30. 30.
    Largier R. Les atteintes hepatiqeus au cours de la sclerodermia. Paris, 1974.Google Scholar
  31. 31.
    Clarke AK, Galbraith RM, Hamilton EB, Williams R. Rheumatic disorders in primary biliary cirrhosis. Ann Rheum Dis. 1978;37:42–47.CrossRefPubMedGoogle Scholar
  32. 32.
    Numata K, Imai R, Yamada H, Takamori K. A case of CREST syndrome associated with lupoid type autoimmune hepatitis and tyroiditis. Rinshou Hifuka. 1989;43:1125–1129.Google Scholar
  33. 33.
    Ishikawa M, Okada J, Shibuya A, Kondo H. CRST syndrome (calcinosis cutis, Raynaud’s phenomenon, sclerodactyly, and telangiectasia) associated with autoimmune hepatitis. Intern Med. 1995;34:6–9.CrossRefPubMedGoogle Scholar
  34. 34.
    Yabe H, Noma K, Tada N, Mochizuki S, Nagano MA. Case of CREST syndrome with rapidly progressive liver damage. Intern Med. 1992;31:69–73.CrossRefPubMedGoogle Scholar
  35. 35.
    Steen VD, Medsger TA Jr. Case–control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis. Arthritis Rheum. 1998;41:1613–1619.CrossRefPubMedGoogle Scholar
  36. 36.
    Ngo Mandag N, Van Gossum M, Rickaert F, Golstein M. Autoimmune hepatitis and CREST syndrome. Rev Med Brux. 2007;28:528–531.PubMedGoogle Scholar
  37. 37.
    Matsumoto T, Morizane T, Aoki Y, et al. Autoimmune hepatitis in primary Sjogren’s syndrome: pathological study of the livers and labial salivary glands in 17 patients with primary Sjogren’s syndrome. Pathol Int. 2005;55:70–76.CrossRefPubMedGoogle Scholar
  38. 38.
    Skopouli FN, Barbatis C, Moutsopoulos HM. Liver involvement in primary Sjögren’s syndrome. Br J Rheumatol. 1994;33:745–748.CrossRefPubMedGoogle Scholar
  39. 39.
    Lindgren S, Manthorpe R, Eriksson S. Autoimmune liver disease in patients with primary Sjögren’s syndrome. J Hepatol. 1994;20:354–358.CrossRefPubMedGoogle Scholar
  40. 40.
    Uddenfeldt P, Danielsson A, Forssell A, Holm M, Ostberg Y. Features of Sjögren’s syndrome in patients with primary biliary cirrhosis. J Intern Med. 1991;230:443–448.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Cumali Efe
    • 1
    • 2
    Email author
  • Ersan Ozaslan
    • 1
  • Narin Nasiroglu
    • 1
  • Hasan Tunca
    • 1
  • Tugrul Purnak
    • 1
  • Emin Altiparmak
    • 1
  1. 1.Department of GastroenterologyNumune Education and Training HospitalAnkaraTurkey
  2. 2.AnkaraTurkey

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