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The role of hypercoagulability in liver fibrogenesis

Lookup NU author(s): Professor Quentin Anstee

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Abstract

The development of hepatic fibrosis on a background of chronic liver injury represents a complex disease trait modulated through the interaction of host genetic factors and environmental influences. Early observations that hepatic inflammation and cirrhosis are associated with the presence of microthrombi within the hepatic vasculature and fibrin/fibrinogen deposition were followed by epidemiological studies showing that carriage of the Factor V Leiden (FvL) mutation, protein C deficiency and increased expression of factor VIII are associated with accelerated progression to cirrhosis in a chronic hepatitis C infection. Additional data suggest that these factors may influence fibrogenesis in many forms of chronic liver disease and extra-hepatic fibrotic processes. Drawing evidence both from liver research and studies of fibrogenesis in other organ systems, two hypotheses may explain how activity of the coagulation cascade influences the rate of hepatic fibrogenesis: tissue ischaemia and parenchymal extinction and direct thrombin mediated stellate cell activation via PAR-1 cleavage. Drawing on preclinical and clinical studies we discuss the evidence for a role for coagulation cascade activity in hepatic fibrogenesis and explore the proposed pathogenic mechanisms that lead to stellate cell activation. The corollary of an association between hypercoagulation and increased fibrosis is that interference with the coagulation cascade may reduce hepatic fibrosis. We conclude this article by examining the implications for future therapeutic intervention. (C) 2011 Elsevier Masson SAS. All rights reserved.


Publication metadata

Author(s): Anstee QM, Dhar A, Thursz MR

Publication type: Article

Publication status: Published

Journal: Clinics and Research in Hepatology and Gastroenterology

Year: 2011

Volume: 35

Issue: 8-9

Pages: 526-533

Print publication date: 14/05/2011

ISSN (print): 2210-7401

ISSN (electronic): 2210-741X

Publisher: Elsevier Masson

URL: http://dx.doi.org/10.1016/j.clinre.2011.03.011

DOI: 10.1016/j.clinre.2011.03.011


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