HCV (hepatitis C virus) has a high propensity to persist and to cause chronic hepatitis C, eventually leading to cirrhosis. Since HCV itself is not cytopathic, liver damage in chronic hepatitis C is commonly attributed to immune-mediated mechanisms. HCV proteins interact with several pathways in the host's immune response and disrupt pathogen-associated pattern recognition pathways, interfere with cellular immunoregulation via CD81 binding and subvert the activity of NK (natural killer) cells as well as CD4+ and CD8+ T-cells. Finally, HCV-specific T-cells become increasingly unresponsive and apparently disappear, owing to several possible mechanisms, such as escape mutations in critical viral epitopes, lack of sufficient help, clonal anergy or expansion of regulatory T-cells. The role of neutralizing antibodies remains uncertain, although it is still possible that humoral immunity contributes to bystander damage of virally coated cells via antibody-dependent cellular cytotoxicity. Cytotoxic lymphocytes kill HCV-infected cells via the perforin/granzyme pathway, but also release Fas ligand and inflammatory cytokines such as IFNγ (interferon γ). Release of soluble effector molecules helps to control HCV infection, but may also destroy uninfected liver cells and can attract further lymphocytes without HCV specificity to invade the liver. Bystander damage of these non-specific inflammatory cells will expand the tissue damage triggered by HCV infection and ultimately activate fibrogenesis. A clear understanding of these processes will eventually help to develop novel treatment strategies for HCV liver disease, independent from direct inhibition of HCV replication.
Skip Nav Destination
Article navigation
February 2007
-
Cover Image
Cover Image
- PDF Icon PDF LinkTable of Contents
Review Article|
January 03 2007
Immunopathogenesis in hepatitis C virus cirrhosis
Ulrich Spengler;
1Department of Internal Medicine 1, University of Bonn, Sigmund-Freud-Strasse 25, Bonn, Germany
Correspondence: Professor Ulrich Spengler (email ulrich.spengler@ukb.uni-bonn.de).
Search for other works by this author on:
Jacob Nattermann
Jacob Nattermann
1Department of Internal Medicine 1, University of Bonn, Sigmund-Freud-Strasse 25, Bonn, Germany
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
June 30 2006
Revision Received:
August 07 2006
Accepted:
August 16 2006
Accepted Manuscript online:
January 03 2007
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society
2007
Clin Sci (Lond) (2007) 112 (3): 141–155.
Article history
Received:
June 30 2006
Revision Received:
August 07 2006
Accepted:
August 16 2006
Accepted Manuscript online:
January 03 2007
Citation
Ulrich Spengler, Jacob Nattermann; Immunopathogenesis in hepatitis C virus cirrhosis. Clin Sci (Lond) 1 February 2007; 112 (3): 141–155. doi: https://doi.org/10.1042/CS20060171
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.