Immunohistochemical Study about the Origin of Bile Ductules Proliferation in Obstructive Liver Disease

ABSTRACT

BACKGROUND: The relationship between bile duct proliferation and portal fibrosis in obstructive liver diseases remains unclear. The purpose of this study is to analyze the relationship between hepatic stellate cells (HSC), hepatocytes and bile ductule proliferation in obstructive liver disease using immunoreactivity for alpha-SMA (alpha-smooth muscle actin), CK7, and CK19. METHODS: We used 20 human tissue samples with hepatic fibrosis due to intrahepatic stones and liver cirrhosis. Immunohistochemical staining was performed using the streptavidin-biotin method. RESULTS: Proliferations of bile ductules at the periphery of the hepatic lobules, and diffuse HSC activation in the perisinusoidal spaces were observed in all cases. Immunoreactivity of the hepatocytes for CK7 and CK19 suggested a possible phenotypic transformation into bile duct epithelium during fibrogenesis. Immunohistochemical-analyses of alpha-SMA expression profiles showed that intralobular HSCs and some hepatocytes underwent early phenotypic changes, and that the accumulation of collagen coincides with that of alpha-SMA-labeled myofibroblasts around portal/septal ductular structures. CONCLUSIONS: Our results showed the possibility of a phenotypic transformation of hepatocytes into bile ductular epithelium. It is suggested that hepatocytes might play a role in bile ductule proliferation in obstructive liver disease.