Correlation between Tgf-Β1 and Fsp-1 Expression in Chronic Viral Hepatitis - an Immunohistochemical Study

Infection with hepatitis C virus (HCV) is the most important stimulus for chronic hepatitis and subsequent progression to cirrhosis and hepatocellular carcinoma. Fibrosis that follows inflammation represents the main complication. One of the mechanisms that could be associated with development of liver fibrosis is epithelial-mesenchymal transition (EMT). Transforming Growth Factor β1 (TGF-β1) is an important mediator of fibrosis and also able to trigger phenotypic changes in EMT. Fibroblast-specific protein 1 (FSP-1), a marker of fibroblasts in organs undergoing tissue remodeling, is used to identify cells that derive from EMT. In this study, we assessed the expression of TGF-β1 and FSP-1 in liver biopsies obtained from HCV-infected patients using immunohistochemistry and correlated them in order to evaluate the relation between fibrosis and EMT in liver disease progression. Staining of liver sections revealed increased amount of type III collagen and clusters of inflammatory cells invading portal spaces. The number of TGF-β1-positive cells was directly proportional to the incidence of liver injury. In cases of mild fibrosis, FSP-1 positive cells were observed in cells lining sinusoids. As fibrosis progressed, increased number of FSP-1 positive fibroblasts, isolated cholangiocytes and hepatocytes was observed. Even EMT via the activation of TGF-β signaling pathway is recognized as a pathogenic mechanism of HCV-induced liver disease, FSP-1 alone couldn’t be used as a valuable marker for cells that undergo EMT.