Parenchymal extinction: coagulation and hepatic fibrogenesis

Observations that hepatic inflammation and cirrhosis are associated with the presence of thrombi within the hepatic microvasculature and fibrin-fibrinogen deposition have led to epidemiologic studies showing that carriage of the factor V Leiden mutation, protein C deficiency, and increased expression of factor VIII are associated with rapid progression to cirrhosis in a chronic hepatitis C virus. Additional data suggest that this process may extend more broadly to progression in many forms of chronic liver disease. This article discusses the evidence for a role for coagulation cascade activity in hepatic fibrogenesis and explores the proposed pathogenic mechanisms including the downstream events of thrombin activation. Interference with either the generation of thrombin or its downstream activity may reduce hepatic fibrosis. Also examined are the implications for future therapeutic intervention.