Molecular Pathways: Hepatitis C Virus, CXCL10, and the Inflammatory Road to Liver Cancer
- 14 March 2013
- journal article
- review article
- Published by American Association for Cancer Research (AACR) in Clinical Cancer Research
- Vol. 19 (6), 1347-1352
- https://doi.org/10.1158/1078-0432.ccr-12-0928
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. Clin Cancer Res; 19(6); 1347–52. ©2012 AACR.Keywords
This publication has 60 references indexed in Scilit:
- Activation of chemokine and inflammatory cytokine response in hepatitis C virus–infected hepatocytes depends on toll-like receptor 3 sensing of hepatitis C virus double-stranded RNA intermediatesHepatology, 2011
- Boceprevir for Previously Treated Chronic HCV Genotype 1 InfectionNew England Journal of Medicine, 2011
- Naturally occurring CD4+ T-cell epitope variants act as altered peptide ligands leading to impaired helper T-cell responses in hepatitis C virus infectionHuman Immunology, 2011
- Pioglitazone, Vitamin E, or Placebo for Nonalcoholic SteatohepatitisNew England Journal of Medicine, 2010
- Pattern Recognition Receptors and InflammationCell, 2010
- CCR5 Deficiency Is a Risk Factor for Early Clinical Manifestations of West Nile Virus Infection but not for Viral TransmissionThe Journal of Infectious Diseases, 2010
- Effects of losartan on hepatic expression of nonphagocytic NADPH oxidase and fibrogenic genes in patients with chronic hepatitis CAmerican Journal of Physiology-Gastrointestinal and Liver Physiology, 2009
- Chemokines in the immunopathogenesis of hepatitis C infectionHepatology, 2008
- Innate immunity induced by composition-dependent RIG-I recognition of hepatitis C virus RNANature, 2008
- Mechanisms of Hepatic FibrogenesisGastroenterology, 2008