The sinusoidal endothelial cells present in the liver (LSECs) are tipically characterized by the presence of pores (fenestrae). During some pathological conditions LSECs undergo "capillarization", a process characterized by loss of fenestrations and acquisition of a vascular phenotype. In chronic liver disease capillarization has been reported to precede the development of fibrosis. LSECs modification in the setting of HCV infection is currently poorly investigated. Considering that HCV accounts for important changes in hepatocytes and in view of the intimate connection between hepatocytes and LSECs, here we set out to study in great detail the LSECs modifications in individuals with HCV-dependent chronic hepatitis. Electron microscopy analysis, and evaluation of CD32, CD31 and caveolin-1 expression showed that in HCV infection LSECs display major morphological changes but maintain their phenotypical identity. Capillarization was observed only in cases at initial stages of fibrosis. Our findings showed that the severity of LSECs modifications appears to be correlated with hepatocytes damage and fibrosis stage providing novel insight in the pathogenesis of HCV-chronic hepatitis.