Immunopathological mechanisms of liver cell injury in chronic hepatitis B virus infection

A. L W F Eddleston, M. Mondelli

Research output: Contribution to journalArticle

Abstract

It is generally accepted that the hepatitis B virus is not cytopathic and that liver cell damage in chronic HBV infection is dependent on the host's immune response directed at viral and self-antigens on the surface of infected hepatocytes. In recent years there have been some advances in the understanding of both the viral antigen display on hepatocytes and the resultant host response. Using fluoresceinated polyclonal and monoclonal antibodies to HBV antigens, HBcAg has been identified as the major viral product expressed on the surface of liver cells isolated from patients with chronic HBV infection. In these patients, both T and non-T cells from peripheral blood have been shown to be cytotoxic to autologous hepatocytes. Blocking studies using polyclonal anti-HBs and anti-HBc antibodies indicate that HBcAg, but not HBsAg, is an important target antigen for T-cell attack, and this has recently been confirmed using monoclonal reagents. The non-T cell cytotoxicity appears to be directed at auto-antigens in a liver membrane lipoprotein complex (LSP), probably through an antibody-dependent (ADCC) mechanism. T-cell bypass mechanisms could be responsible for the production of autoantibodies to these normal membrane components. Both these mechanisms of cytolysis are found, most often, in patients with active viral replication in the HBeAg-positive phase of chronic HBV infection. This is presumably because hepatocytes containing free HBV-DNA and expressing HBcAg on their surface will be most susceptible to T-cell attack, while those with integrated HBV-DNA only express HBsAg and are relatively protected. It is possible that this selective pressure assists in the transition to the HBsAg-positive/anti-HBe-positive carrier with relatively inactive liver disease, whether this occurs spontaneously or during anti-viral therapy.

Original languageEnglish
JournalJournal of Hepatology
Volume3
Issue numberSUPPL. 2
DOIs
Publication statusPublished - 1986

ASJC Scopus subject areas

  • Gastroenterology

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