title: Anti-platelet therapy in the prevention of hepatitis B virus-associated hepatocellular carcinoma.
abstract: Previous studies in mouse models of self-limited viral hepatitis showed that platelets contribute to acute liver damage by promoting the intrahepatic accumulation of virus-specific CD8 T cells and, secondarily, virus-non-specific inflammatory cells. Built on these observations, a recent preclinical study took advantage of a previously established hepatitis B virus (HBV) transgenic mouse model of immune-mediated chronic hepatitis that progresses to hepatocellular carcinoma (HCC), to demonstrate that clinically achievable doses of the anti-platelet drugs aspirin and clopidogrel - administered continuously after the onset of liver disease - can prevent hepatocarcinogenesis and greatly improve overall survival. These outcomes were preceded by and associated with reduced hepatic accumulation of virus-specific CD8 T cells and virus-non-specific inflammatory cells, reduced hepatocellular injury and hepatocellular proliferation, and reduced severity of liver fibrosis. The observation that anti-platelet therapy inhibits HCC development identifies platelets as key players in the pathogenesis of HBV-associated liver cancer and supports the notion that a sustained immune-mediated necroinflammatory liver disease is sufficient to trigger HCC. The results abovementioned and their clinical implications are discussed in this report.
authors.affiliation: Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Milan 20132, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Sitia
authors.forename: Matteo
authors.initials: M
authors.lastname: Iannacone
authors.forename: Luca G
authors.initials: LG
authors.lastname: Guidotti
mesh_terms: D000818:Animals; D001241:Aspirin / Q000494:pharmacology / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000517:prevention & control* / Q000821:virology*; D049109:Cell Proliferation / Q000187:drug effects; D000077144:Clopidogrel; D004195:Disease Models, Animal; D006515:Hepatitis B virus; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000473:pathology; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology / Q000517:prevention & control* / Q000821:virology*; D051379:Mice; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin
keywords: Anti-platelet drugs; CD8 T cells; Hepatitis B virus; Hepatocellular carcinoma; Platelets; Viral hepatitis