Ultrastructure of the Ito cells in liver disease associated with fibrosis

The ultrastructure of Ito cells was examined in percutaneous needle liver biopsies of 36 patients. In three cases the liver was normal. Four specimens showed mild or moderate fatty degeneration. In the rest of the liver samples various types of fibrosis were seen: in four cases portal, in ten centrilobular, in eight periportal fibrosis and in five cases cirrhosis. In the normal liver Ito cells occurred not only in the Disse spaces but also in the walls of the terminal hepatic venules. In livers showing portal fibrosis the ultrastructure of Ito cells was similar to that seen in the normal liver. In the fibrotic areas of liver samples showing centrilobular or periportal fibrosis or cirrhosis Ito cells localized inside the fibrotic tissue and along the border between the connective tissue and hepatocytes. These interstitial Ito cells contained few lipid, abundant rough endoplasmic reticulum with dilated tubules filled by a flocculant material, well developed Golgi complexes and often bundles of 5 nm thick filaments with densities. These cells also known as activated Ito cells were in places surrounded by immature collagen fibrils and basement membrane fragments. There was a close contact between activated Ito cells and lymphocytes. The ultrastructure of Ito cells localizing in non-fibrotic areas did not differ from that seen in normal liver lobules. These observations suggest that Ito cells are related to fibroblasts and myofibroblasts and play an important role in the pathogenesis of liver fibrosis in humans.