H epatic fibrosis is a major histological finding associated with the progression of chronic liver disease to cirrhosis; it is characterized by increased deposition of components of the extracellular matrix (ECM), in particular fibrillar collagens type I and type III. 1 Hepatic stellate cells (HSC) are currently considered to be one of the major sources of ECM proteins in the liver; expansion of their pool is a key step in the fibrogenic process. 2 Following hepatic injury, HSC develop a myofibroblast-like phenotype, characterized by a reduced content of vitamin A, increased proliferation and migration, enhanced expression of matrix protein, and production of matrix metalloproteinases (MMPs). 3 Evidence from experimental and clinical studies indicates that production of reactive oxygen species (ROS) and lipid peroxidation of cell membranes are often associated with the development of hepatic fibrogenesis and

Thrombin is generated during tissue damage in several organs, including the liver, and participates in the process of tissue repair through proteolytic activation of a specific thrombin receptor (TR). The aim of this study was to investigate TR expression in human liver by immunohistochemistry and in situ hybridization. In normal liver, immunostaining for TR was present in the endothelial lining of the hepatic sinusoids. During chronic hepatitis, several cells expressing the TR were detected in the inflammatory infiltrate of portal tracts. In cirrhosis with chronic active hepatitis, expression of the TR was also present in mesenchymal cells of fibrous septa. TR expression was markedly up-regulated during fulminant hepatitis, with the highest expression in mesenchymal cells in areas of regeneration. Up-regulation of TR expression was associated with increased levels of TR messenger RNA (mRNA), as assessed by in situ hybridization and RNAse protection assay of liver RNA. Immunostaining of serial sections using specific cellular markers showed that different nonparenchymal cells contribute to TR expression during liver injury. TR expression was also shown in cultured human hepatic stellate cells, with increasing signal comparing activated versus quiescent cells. Because thrombin is rapidly generated after tissue damage, regulated TR expression may be involved in tissue remodeling and/or scarring during liver damage. (HEPATOLOGY 1998;27:462-471.)

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