title: Molecular pathways: hepatitis C virus, CXCL10, and the inflammatory road to liver cancer.
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.
authors: Pathobiology Program, Department of Global Health, University of Washington, Seattle, Washington 98104, USA.
authors: Jessica
authors: J
authors: Brownell
authors: Stephen J
authors: SJ
authors: Polyak
mesh_terms: D024201:Bystander Effect; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000821:virology; D054357:Chemokine CXCL10 / Q000378:metabolism*; D005355:Fibrosis; D016174:Hepacivirus / Q000378:metabolism / Q000472:pathogenicity; D019698:Hepatitis C, Chronic / Q000473:pathology / Q000821:virology; D022781:Hepatocytes / Q000378:metabolism / Q000821:virology; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D007372:Interferons / Q000008:administration & dosage*; D008103:Liver Cirrhosis / Q000473:pathology / Q000821:virology; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000821:virology
chemical_list: C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D007372:Interferons