Immunohistochemical study on phenotypical changes of hepatocytes in liver disease with reference to extracellular matrix composition

Aims/Background: Extracellular matrix (ECM) may affect the function and phe notype of hepatocytes. Phenotypic changes of hepatocytes in diseased liver were investigated with reference to ECM composition. Methods: Immunohistoch emistry was performed on biopsied liver samples from chronic viral hepatiti s (CVH), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (P SC) and normal patients, using monoclonal antibodies for laminin, type IV c ollagen, cytokeratin 19 (CK19) and epithelial glycoprotein (EGP), a protein homologous to nidogen. Results: In normal controls, both EGF and CK 19 wer e expressed exclusively on biliary epithelia. Laminin and type IV collagen were expressed around portal bile ducts and blood vessels. Although type IV collagen was expressed in Disse's space, laminin was scarcely expressed. I n all pathological livers, both EGP and CK 19 were expressed in proliferate d bile ductules. In CVH with piecemeal necrosis, EGP was expressed on perip ortal hepatocytes, while CK19 expression was limited to a few hepatocytes. Laminin was expressed in Disse's space of periportal sinusoids, where EGP w as expressed on hepatocytes. EGP expression on hepatocytes and laminin depo sition in Disse's space were rare in PBC and PSC liver. Conclusion: These r esults suggest that hepatocytes transform into a phenotype similar to bilia ry epithelia and, laminin deposition in Disse's space (capillarization of s inusoids) may play a role in this phenotypic change.