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Bile Duct Ligation in Mice: Induction of Inflammatory Liver Injury and Fibrosis by Obstructive Cholestasis
Published on: February 10, 2015
[Liver fibrosis. 1 (author's transl)]
Abstract:
The mortality of liver cirrhosis has doubled during the past two decades and is still increasing in most of the European countries. One important feature and precursor of liver cirrhosis is liver fibrosis. Its aetiology includes a wide spectrum of well known causes, in Europe most frequently alcohol, virus infection, and chemical agents. The pathomechanism of liver fibrosis is unknown. Diagnostic and therapeutic approaches for early detection and treatment have been recently developed applying the results of pathobiochemical, cellular and clinical research. The composition of the increased hepatic connective tissue suggests the involvement of myofibroblasts and shows similarities to atherosclerotic plaques and lung fibrosis. The isolation, purification and cultivation of cells from liver biopsies offers new avenues for the study of fibroplastic cells. Clinical studies are now facilitated, since products of the collagen synthetic pathway -- procollagen peptides--can be measured in serum with a sensitive radioimmunoassay. Further prospective studies including additional parameters of fibroplasia, such as N-acetyl-beta-D-glucosaminidase, lysyloxidase and prolylhydroxylase will have to demonstrate the diagnostic value of such methods. Even today, they should be applied in therapeutic trials of chronic fibrotic liver diseases. Better knowledge of the molecular regulation of connective tissue, and the use of new animal models and cellular system support a successful search for new therapeutic tools. Above all, limitation of alcohol consumption, vaccination for viral hepatitis and elimination of chemical agents offer the prevention of fibrosis, which calls for major efforts on a nation-wide scale.
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