GFAP expression in the liver as an early marker of stellate cells activation

The activation of hepatic stellate cells is the conversion of quiescent cells into proliferative, contractile, and fibrogenic myofibroblasts. The alpha-smooth muscle actin is a well known marker of hepatic stellate cells activation. On the other hand, the Glial Fibrillary Acidic Protein expression is a key step in the astrocytes differentiation and constitutes the hallmark response of astrocytes to injury. Glial Fibrillary Acidic Protein expression was reported in quiescent stellate cells in vivo, with an increased expression in the acute response to injury in the rat, and a down-regulation in the chronic one. This study aims to evaluate the morphologic characteristics, distribution and percentage of Glial Fibrillary Acidic Protein expressing cells in normal and injured human livers. Human liver biopsies (n=32) were divided in three groups: 1) donors liver; 2) chronic hepatitis C-virus related; 3) post-viral hepatitis cirrhosis. Samples were immunostained with anti- alpha-smooth muscle actin and anti- Glial Fibrillary Acidic Protein antibody. Subsequently they were semi-quantitatively evaluated. Liver fibrosis was quantified by morphometric analysis. In chronic hepatitis livers and in the cirrhotic ones, hepatic stellate cells became larger with long cytoplasmic processes. The alpha-smooth muscle actin -positive stellate cells increase and expand from areas of piecemeal necrosis to the entire residual parenchyma with the progression of the fibrosis. By contrast Glial Fibrillary Acidic Protein-positive stellate cells are more evenly distributed in the earlier stages and confined to the periphery of the hepatic lobule in the advanced ones. Also some endothelial cells were Glial Fibrillary Acidic Protein positive in vessels of the expanding septa and at the edges of cirrhotic nodules. Glial Fibrillary Acidic Protein expression in the liver is probably linked to the fine modulation of the cytoskeleton during the formation of cytoplasmic processes in both stellate cells and endothelial cells. In the latter Glial Fibrillary Acidic Protein expression might be related to the remodelling of the vascular bed that occurs during the response to injuries. Otherwise in hepatic stellate cells it seems to be a marker related with the acquisition of contractile properties in a subpopulation more closely associated with precocious stages of the fibrosis.