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Cited by 70Hepatitis C virus researchLiver physiology and pathologyChemokine receptors and signaling

Molecular pathways: hepatitis C virus, CXCL10, and the inflammatory road to liver cancer

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Brownell, Jessica, Polyak, Stephen J.·2013·Clinical Cancer Research
DOI 10.1158/1078-0432.ccr-12-0928PMC PMC3602344
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Abstract

An estimated 170 million people worldwide are chronically infected with the hepatitis C virus (HCV), which is characterized histologically by a persistent immune and inflammatory response that fails to clear HCV from hepatocytes. This response is recruited to the liver, in part, by the chemokine CXCL10, the serum and intrahepatic levels of which have been inversely linked to the outcome of interferon-based therapies for hepatitis C. Bystander tissue damage from this ineffective response is thought to lead to increased hepatocyte turnover and the development of fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). However, CXCL10 is traditionally viewed as an orchestrator of the angiostatic and antitumor immune response. In this review, we will explore this duality and the pathways by which CXCL10 is produced by hepatocytes during HCV infection, its effects on resident and infiltrating immune cells, and how deregulation of these cell populations within the liver may lead to chronic liver inflammation. We will also discuss potential host-directed therapies to slow or reverse HCV-induced inflammation that leads to fibrosis, cirrhosis, and HCCs.

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Cited by

Sorted by citations

Authors
Brownell, J., & Polyak, S. J.
Affiliations
University of Washington (US)
Corresponding author
Polyak, Stephen J.
ORCID
Polyak, Stephen J.
Venue
Clinical Cancer Research
Publisher
American Association for Cancer Research (AACR)
Published
2013-03-14
Volume
19
Issue
6
Pages
1347-1352
ISSN
  • 1078-0432 (ISSN-L)
  • 1557-3265
DOI
10.1158/1078-0432.ccr-12-0928
PMC
PMC3602344
OpenAlex
W2112473152
Cited by
70
References
0
Citations by year
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FWCI
1.32
Type
journal article
Language
en
Open access
Locations
  • Clinical Cancer Research (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Allergy and Infectious Diseases (T32AI007509, U19AI066328)
Topics
  • Health Sciences › Medicine › Hepatology › Hepatitis C virus research
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
Keywords
hepatitis C virus, CXCL10, hepatocellular carcinoma, chronic liver inflammation, liver fibrosis, liver cirrhosis, chemokines, interferon therapy, hepatocyte turnover, angiogenesis, antitumor immunity, host-directed therapy, immune cell infiltration
MeSH terms
Fibrosis, Carcinoma, Hepatocellular, Humans, Inflammation, Interferons, Liver Cirrhosis, Liver Neoplasms, Hepacivirus, Hepatitis C, Chronic, Hepatocytes, Bystander Effect, Chemokine CXCL10

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