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Canadian Journal of Gastroenterology - Volume 14 2000, Issue 5, Pages 429-439

Mini-Review Department of Gastroenterology and Hepatology, Hannover Medical School, Germany

Received 7 December 1998; Revised 11 December 1998

Copyright © 2000 Hindawi Publishing Corporation. This open-access article is distributed under the terms of the Creative Commons Attribution Non-Commercial License CC BY-NC, which permits reuse, distribution and reproduction of the article, provided that the original work is properly cited and the reuse is restricted to noncommercial purposes.


Cytochromes P450 CYPs and UDP-glucuronosyltransferases UGTs are targets of autoantibodies in several hepatic and extrahepatic autoimmune diseases. Autoantibodies directed against hepatic CYPs and UGTs were first detected by indirect immunofluorescence as antiliver and-or kidney microsomal antibodies. In autoimmune hepatitis AIH type 2, liver and-or kidney microsomal LKM type 1 autoantibodies are detected and are directed against CYP2D6. About 10% of AIH-2 sera further contain LKM-3 autoantibodies directed against family 1 UGTs. Chronic infections by hepatitis C virus and hepatitis delta virus may induce several autoimmune phenomena, and multiple autoantibodies are detected. Anti-CYP2D6 autoantibodies are detected in up to 4% of patients with chronic hepatitis C, and anti-CYP2A6 autoantibodies are detected in about 2% of these patients. In contrast, 14% of patients with chronic hepatitis delta virus infections generate anti-UGT autoantibodies. In a small minority of patients, certain drugs are known to induce immune-mediated, idiosyncratic drug reactions, also known as ’drug-induced hepatitis’. Drug-induced hepatitis is often associated with autoantibodies directed against hepatic CYPs or other hepatic proteins. Typical examples are tienilic acid-induced hepatitis with anti-CYP2C9, dihydralazine hepatitis with anti-CYP1A2, halothane hepatitis with anti-CYP2E1 and anticonvulsant hepatitis with anti-CYP3A. Recent data suggest that alcoholic liver disease may be induced by mechanisms similar to those that are active in drug-induced hepatitis. Autoantibodies directed against several CYPs are further detected in sera from patients with the autoimmune polyglandular syndrome type 1. Patients with autoimmune polyglandular syndrome type 1 with hepatitis often develop anti-CYP1A2; patients with adrenal failure develop anti-CYP21, anti- CYP11A1 or CYP17; and patients with gonadal failure develop anti-CYP11A1 or CYP17. In idiopathic Addison disease, CYP21 is the major autoantigen.

Autor: Petra Obermayer-Straub, Christian Peer Strassburg, and Michael Peter Manns



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