Semin Liver Dis 2007; 27: 140-151 DOI: 10.1055/s-2007-979467
Copyright © 2007 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.
The Impact of Autoimmunity on Hepatocytes
Diego Vergani1, Giorgina Mieli-Vergani1
1 Institute of Liver Studies, King's College London School of Medicine at King's College Hospital, London, United Kingdom

ABSTRACT

In this article, the impact of autoimmunity on the hepatocyte is analyzed in three distinct settings: classical autoimmune hepatitis, chronic hepatitis C virus infection with autoimmune manifestations, and de novo autoimmune hepatitis after liver transplantation. (1) Classical autoimmune hepatitis: Using as model autoimmune hepatitis type 2, whose main autoantigen is known, complementary aspects of the autoimmune response are revisited, including the targeting of discrete antigenic regions by humoral and cellular effectors of damage and a defect in the counterbalancing immunoregulatory mechanisms. (2) Chronic hepatitis C virus infection: This condition provides clues to the possible role of viruses as triggers of autoimmunity. The interaction between hepatitis C virus and its receptor on B lymphocytes is the likely trigger of a polyclonal activation leading to the production of autoantibodies. These appear not to be an epiphenomenon but to be markers of hepatocyte damage. (3) De novo autoimmune hepatitis after liver transplantation: The intriguing observation that autoimmune hepatitis can arise de novo after liver transplantation is presented and its possible pathogenic mechanisms are discussed.

KEYWORDS

Autoimmune hepatitis - T regulatory cells - autoreactive T cells - autoantibodies - hepatitis C virus infection