Coagulation and fibrosis in chronic liver disease

Calvaruso, V; Maimone, S; Gatt, A; Tuddenham, E; Thursz, M; Pinzani, M; Burroughs, A K
December 2008
Gut;Dec2008, Vol. 57 Issue 12, p1722
Academic Journal
In the hepatic tissue repair mechanism, hepatic stellate cells (HSCs) are recruited at the site of injury and their changes reflect paracrine stimulation by all neighbourinç cell types, including sinusoidal endothelial cells, Kupffer cells, hepatocytes, platelets and leucocytes. Thrombin converts circulating fibrinogen to fibrin, promotes platele aggregation, is a potent activator of endothelial cells, act as a chemoattractant for inflammatory cells and is a mitogen and chemoattractant for fibroblasts and vascul~ smooth muscle cells. Most of the cellular effects elicite by thrombin are mediated via a family of widely expresse G-protein-coupled receptors termed protease activated receptors (PARs). All known members of the PAR famil stimulate cell proliferation/activation in a rat HSC line. Thrombin receptors are constitutively expressed in the liver, and their expression increases in parallel with the severity and/or the duration of liver disease. In human studies, thrombotic risk factors were found to be independently associated with the extent of fibrosis; severity of hepatitis C virus (HCV(-associated liver diseas appears to be less in patients with haemoihilia when compared with those with HCV alone. Several studies, based mostly on rat models, demonstrate that anti- coagulants or antiplatelet agents prevent hepatic necrosi and fibrosis by acting on HSCs. These drugs could be therapeutic agents in patients with chronic liver diseasE and specific studies should be initiated.


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