Thrombin activation and liver inflammation in advanced hepatitis C virus infection

Abstract

Hepatitis C virus (HCV) infection is associated with increased thrombotic risk. Several mechanisms are involved including direct endothelial damage by the HCV virus, with activation of tissue factor, altered fibrinolysis and increased platelet aggregation and activation. In advanced stages, chronic HCV infection may evolve to liver cirrhosis, a condition in which alterations in the portal microcirculation may also ultimately lead to thrombin activation, platelet aggregation, and clot formation. Therefore in advanced HCV liver disease there is an increased prevalence of thrombotic phenomena in portal vein radicles. Increased thrombin formation may activate hepatic stellate cells and promote liver fibrosis. In addition, ischemic changes derived from vascular occlusion by microthrombi favor the so called parenchymal extinction, a process that promotes collapse of hepatocytes and the formation of gross fibrous tracts. These reasons may explain why advanced HCV infection may evolve more rapidly to end-stage liver disease than other forms of cirrhosis.

Keywords: Coagulation; Liver cirrhosis; Hepatitis C virus; Fibrogenesis; Parenchymal extinction; Portal thrombosis; Protein C

Core tip: Liver cirrhosis may be considered a prothrombotic condition despite it being associated with a low platelet count and deranged synthesis of clotting factors. When hepatitis C virus (HCV) is the etiological factor of liver cirrhosis, intrahepatic coagulation may be enhanced by several direct actions of HCV on the clotting system, platelet aggregation, and altered anticoagulation. The excessive thrombin generation may be related to increased fibrogenesis both by a direct effect of thrombin on hepatic stellate cells and fibrosis related to ischemic parenchymal extinction.