Autoimmune hepatitis: Associated extrahepatic disorders
- Michael A Heneghan, MD, MMedSc, FRCPI
Michael A Heneghan, MD, MMedSc, FRCPI
- Consultant Hepatologist & Reader in Hepatology
- Clinical Director for Liver Services
- Institute of Liver Studies, King's College Hospital
- Section Editor
- Sanjiv Chopra, MD, MACP
Sanjiv Chopra, MD, MACP
- Editor-in-Chief — Gastroenterology/Hepatology
- Section Editor — General Hepatology
- Section Editor — Gallbladder and Biliary Tract Disease
- Professor of Medicine
- Harvard Medical School
- Senior Consultant in Hepatology
- James Tullis Firm Chief
- Beth Israel Deaconess Medical Center
Autoimmune hepatitis is a chronic hepatitis of unknown etiology characterized by immunologic and autoimmunologic features (see "Autoimmune hepatitis: Clinical manifestations and diagnosis"). 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.
This topic will review the extrahepatic disorders associated with autoimmune hepatitis. The hepatic manifestations, diagnosis, and treatment of autoimmune hepatitis are discussed elsewhere. (See "Autoimmune hepatitis: Clinical manifestations and diagnosis" and "Autoimmune hepatitis: Treatment".)
Several extrahepatic disorders associated with autoimmune hepatitis (AIH) have been described (table 1) and are seen in both type 1 and type 2 AIH (table 2) [1-4]. 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 with 22 percent of 63 patients with chronic viral hepatitis . 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 antibodies to detect celiac disease or routine proctosigmoidoscopy for the detection of ulcerative colitis).
Concurrent extrahepatic autoimmune disorders associated with AIH include autoimmune thyroiditis, diabetes, rheumatoid arthritis, and ulcerative colitis (ranging from approximately 20 to 49 percent of patients with AIH in various reports from around the world) [1-4,6-12]. Up to 43 percent of patients with AIH report a family history of another autoimmune disease in their first-degree relatives, commonly thyroid disease and type 1 diabetes .
- Krawitt EL. Autoimmune hepatitis. N Engl J Med 2006; 354:54.
- 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.
- Muratori P, Grnito A, Quarneto C, et al. Autoimmune hepatitis in Italy: The Bologna experience. J Hepatology 2009; 52:1210.
- Teufel A, Weinmann A, Kahaly GJ, et al. Concurrent autoimmune diseases in patients with autoimmune hepatitis. J Clin Gastroenterol 2010; 44:208.
- Czaja AJ, Carpenter HA, Santrach PJ, Moore SB. Genetic predispositions for the immunological features of chronic active hepatitis. Hepatology 1993; 18:816.
- Abdo A, Meddings J, Swain M. Liver abnormalities in celiac disease. Clin Gastroenterol Hepatol 2004; 2:107.
- 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.
- 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.
- Perdigoto R, Carpenter HA, Czaja AJ. Frequency and significance of chronic ulcerative colitis in severe corticosteroid-treated autoimmune hepatitis. J Hepatol 1992; 14:325.
- Bloom JN, Rabinowicz IM, Shulman ST. Uveitis complicating autoimmune chronic active hepatitis. Am J Dis Child 1983; 137:1175.
- Abe M, Mashiba T, Zeniya M, et al. Present status of autoimmune hepatitis in Japan: a nationwide survey. J Gastroenterol 2011; 46:1136.
- Peng M, Li Y, Zhang M, et al. Clinical features in different age groups of patients with autoimmune hepatitis. Exp Ther Med 2014; 7:145.
- Gregorio GV, Portmann B, Reid F, et al. Autoimmune hepatitis in childhood: a 20-year experience. Hepatology 1997; 25:541.
- 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.
- Biasi D, Caramasch P, Carletto A, et al. Sjögren's syndrome associated with autoimmune hepatitis. A case report. Clin Rheumatol 1997; 16:409.
- 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.
- 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.
- 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.
- Maeda M, Kanayama M, Hasumura Y, et al. Case of mixed connective tissue disease associated with autoimmune hepatitis. Dig Dis Sci 1988; 33:1487.
- Allen-Mersh TG. Weber-Christian panniculitis and auto-immune disease: a case report. J Clin Pathol 1976; 29:144.
- 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.
- 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.
- el Younis CM, Min AD, Fiel MI, et al. Autoimmune hepatitis in a patient with sickle cell disease. Am J Gastroenterol 1996; 91:1016.
- 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.
- 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.
- 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.
- 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.
- Pensati L, 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.
- 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.
- Mistilis SP, Blackburn CR. Active chronic hepatitis. Am J Med 1970; 48:484.
- Golding PL, Smith M, Williams R. Multisystem involvement in chronic liver disease. Studies on the incidence and pathogenesis. Am J Med 1973; 55:772.
- Wat H, Haber RM. Trends in the Association between Pyoderma Gangrenosum and Autoimmune Hepatitis: Case Report and Review of the Literature. J Cutan Med Surg 2014; 18:345.
- Halac U, Al Dhaybi R, Powell J, et al. Unusual association between autoimmune hepatitis and severe pyoderma gangrenosum. J Pediatr Gastroenterol Nutr 2010; 50:219.
- Mirzaagha F, Azali SH, Islami F, et al. Coeliac disease in autoimmune liver disease: a cross-sectional study and a systematic review. Dig Liver Dis 2010; 42:620.
- Volta U, De Franceschi L, Molinaro N, et al. Frequency and significance of anti-gliadin and anti-endomysial antibodies in autoimmune hepatitis. Dig Dis Sci 1998; 43:2190.
- Villalta D, Girolami E, Alessio MG, et al. Autoantibody Profiling in a Cohort of Pediatric and Adult Patients With Autoimmune Hepatitis. J Clin Lab Anal 2016; 30:41.
- van Gerven NM, Bakker SF, de Boer YS, et al. Seroprevalence of celiac disease in patients with autoimmune hepatitis. Eur J Gastroenterol Hepatol 2014; 26:1104.
- Vajro P, Paolella G, Maggiore G, Giordano G. Pediatric celiac disease, cryptogenic hypertransaminasemia, and autoimmune hepatitis. J Pediatr Gastroenterol Nutr 2013; 56:663.
- Nastasio S, Sciveres M, Riva S, et al. Celiac disease-associated autoimmune hepatitis in childhood: long-term response to treatment. J Pediatr Gastroenterol Nutr 2013; 56:671.
- Wang N, Shen N, Vyse TJ, et al. Selective IgA deficiency in autoimmune diseases. Mol Med 2011; 17:1383.
- Duchini A, McHutchison JG, Pockros PJ. LKM-positive autoimmune hepatitis in the western United States: a case series. Am J Gastroenterol 2000; 95:3238.