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Extrahepatic manifestations of autoimmune hepatitis

INTRODUCTION

Autoimmune hepatitis (AIH) is a chronic hepatitis of unknown etiology characterized by immunologic and autoimmunologic features . (See "Clinical manifestations and diagnosis of autoimmune hepatitis".) In the spectrum of autoimmune disease, classified from organ-specific to non-organ-specific, autoimmune liver diseases fall somewhere in the middle. The diseases are usually confined to the liver but can be associated with a number of other autoimmune diseases.

EXTRAHEPATIC DISORDERS

Several extrahepatic disorders associated with AIH have been described (table 1). Concurrent immunologic diseases are more common with AIH than with viral hepatitis. One prospective study, for example, found that concurrent immunologic disease was present in 38 percent of 122 patients with AIH compared to 22 percent of 63 patients with chronic viral hepatitis [1]. The nature of the extrahepatic diseases was the same in both groups.

The associated diseases may antedate the appearance of AIH or occur after the diagnosis of the liver disease is established. The clinical expression of the associated disease can be extremely variable and at times may even be occult and unrecognized unless specifically sought (such as measurement of antiendomysial antibodies to detect celiac disease or routine proctosigmoidoscopy for the detection of ulcerative colitis).

Extrahepatic disorders are seen in both type 1 and type 2 AIH (table 2) (see "Classification of autoimmune hepatitis" [2]. Associated diseases are seen in both types of AIH [3,4].

Antiendomysial antibodies, anti-gluten antibodies and anti-tissue transglutaminase antibodies reflect the co-existence of celiac disease in AIH and other autoimmune liver diseases [5-7]. The prevalence of celiac disease in AIH may be as high as 10 percent. Because liver transglutaminase levels may be elevated in patients with liver disease, it has been hypothesized that circulating anti-tissue transglutaminase levels may merely reflect liver damage; more likely they reflect the co-existence of celiac sprue and AIH.
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References Top
  1. Czaja, AJ, Carpenter, HA, Santrach, PJ, Moore SB. Genetic predispositions for the immunologic features of chronic active hepatitis. Hepatology 1993; 18:816.
  2. Krawitt, EL. Autoimmune hepatitis. N Engl J Med 2006; 354:54.
  3. Bittencourt, PL, Farias, AQ, Porta, G, et al. Frequency of concurrent autoimmune disorders in patients with autoimmune hepatitis: effect of age, gender, and genetic background. J Clin Gastroenterol 2008; 42:300.
  4. Muratori, P, Grnito, A, Quarneto, C, et al. Autoimmune hepatitis in Italy: The Bologna experience. J Hepatology 2009; 52:1210.
  5. Abdo, A, Meddings, J, Swain, M. Liver abnormalities in celiac disease. Clin Gastroenterol Hepatol 2004; 2:107.
  6. Caprai, S, Vajro, P, Ventura, A, et al. Autoimmune liver disease associated with celiac disease in childhood: a multicenter study. Clin Gastroenterol Hepatol 2008; 6:803.
  7. Rubio-Tapia, A, Abdulkarim, AS, Wiesner, RH, et al. Celiac disease autoantibodies in severe autoimmune liver disease and the effect of liver transplantation. Liver Int 2008; 28:467.
  8. Perdigoto, R, Carpenter, HA, Czaja, AJ. Frequency and significance of chronic ulcerative colitis in severe corticosteroid-treated autoimmune hepatitis. J Hepatol 1992; 14:325.
  9. Bloom, JN, Rabinowicz, IM, Shulman ST. Uveitis complicating autoimmune chronic active hepatitis. Am J Dis Child 1983; 137:1175.
  10. Czaja, AJ, Davis, GL, Ludwig, J, et al. Autoimmune features as determinants of prognosis in steroid-treated chronic active hepatitis of uncertain etiology. Gastroenterology 1983; 85:713.
  11. Biasi, D, Caramasch, P, Carletto, A, et al. Sjögren's syndrome associated with autoimmune hepatitis. A case report. Clin Rheumatol 1997; 16:409.
  12. Ecoiffier, EB, Tubery, M, Adoue, D, et al. Systemic manifestations of primary Gougerot-Sjögren syndrome. Nature and incidence apropos of 34 cases. Presse Med 1997; 26:995.
  13. Tomsic, M, Ferlan-Marolt, V, Kveder, T, et al. Mixed connective tissue disease associated with autoimmune hepatitis and thyroiditis. Ann Rheum Dis 1992; 51:544.
  14. Wada, T, Motoo, Y, Ohmizo, R, et al. Association of mixed connective tissue disease, Sjögren's syndrome and autoimmune hepatitis: Report of a case. Jpn J Med 1991; 30:278.
  15. Maeda, M, Kanayama, M, Hasumura, Y, et al. Case of mixed connective tissue disease associated with autoimmune hepatitis. Dig Dis Sci 1988; 33:1487.
  16. Allen-Mersh, TG. Weber-Christian panniculitis and auto-immune disease: A case report. J Clin Pathol 1976; 29:144.
  17. 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.
  18. Chuang E, Ruchelli, E, Mulberg, AE. Autoimmune liver disease and sickle cell anemia in children: A report of three cases. J Pediatr Hematol Oncol 1997; 19:159.
  19. el Younis, CM, Min, AD, Fiel, MI, et al. Autoimmune hepatitis in a patient with sickle cell disease. Am J Gastroenterol 1996; 91:1016.
  20. Al-Chalabi, T, Boccato, S, Portmann, BC, et al. Autoimmune hepatitis (AIH) in the elderly: a systematic retrospective analysis of a large group of consecutive patients with definite AIH followed at a tertiary referral centre. J Hepatol 2006; 45:575.
  21. 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.
  22. Sacher, M, Blümel, P, Thaler, H, Manns, M. Chronic active hepatitis associated with vitiligo, nail dystrophy, alopecia and a new variant of LKM antibodies. J Hepatol 1990; 10:364.
  23. Clemente, MG, Meloni, A, Obermayer-Straub, P, et al. Two cytochromes P450 are major hepatocellular autoantigens in autoimmune polyglandular syndrome type 1. Gastroenterology 1998; 114:324.
  24. Pensati, Costanzo, A, Ianni, A, et al. Fas/Apo1 mutations and autoimmune lymphoproliferative syndrome in a patient with type 2 autoimmune hepatitis. Gastroenterology 1997; 113:1384.
  25. Gregorio, GV, Portmann, B, Reid, F, et al. Autoimmune hepatitis in childhood: A 20-year experience. Hepatology 1997; 25:541.
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