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.
Anstee
Quentin M
QM
Department of Academic Medicine, St Mary+s Hospital Campus, Imperial College London, 10th Floor, QEQM Building, Praed Street, London W2 1PG, UK. Electronic address: q.anstee@imperial.ac.uk.
Wright
Mark
M
Department of Hepatology, Southampton General Hospital, Southampton, UK.
Goldin
Robert
R
Department of Histopathology, St Mary's Hospital Campus, Imperial College London, 10th Floor, QEQM Building, Praed Street, London W2 1PG, UK.
Thursz
Mark R
MR
Department of Academic Medicine, St Mary+s Hospital Campus, Imperial College London, 10th Floor, QEQM Building, Praed Street, London W2 1PG, UK.
D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use; D001777:Blood Coagulation; D055166:Hepatic Stellate Cells / Q000378:metabolism; D019698:Hepatitis C, Chronic / Q000150:complications; D006801:Humans; D008099:Liver / Q000503:physiopathology*; D008103:Liver Cirrhosis / Q000453:epidemiology / Q000209:etiology* / Q000503:physiopathology* / Q000628:therapy; D044463:Receptor, PAR-1 / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism
D000925:Anticoagulants; D044463:Receptor, PAR-1; D013917:Thrombin