Expression of HBs- and HBc-antigen in neoductular epithelium in chronic active hepatitis B. A further support for hepato-ductular metaplasia.

Biopsy specimens (n = 61) from patients with chronic active hepatitis B and progressive fibrosis (n = 61) were studied immunohistochemically to obtain information about the histogenesis of neoductules. All the biopsies contained clusters of oval-shaped cells often arranged in the form of neoductular aggregates. These expressed cytokeratins 7 and 19 which in the normal liver are found only in bile duct and ductular epithelium but not in hepatocytes. Using monoclonal and polyclonal antibodies both hepatocytes and these oval neoductular cells were found to express HBs- and HBc-antigen in 15% and 20% of the biopsies, respectively. Taking into consideration the strong hepatocytotropism of the hepatitis B virus, the expression of HBV-antigens in neoductular cells suggest their development from HBV-infected hepatocytes. Using proliferating cell nuclear antigen (PCNA) as a marker of cell proliferation positive staining was detected only in hepatocytes but not in neoductular cells. Taken together findings further support the concept of hepatoductular metaplasia in the histogenesis of so-called "proliferating" ductules. In general the data show that hepatitis B virus infection does not prevent hepatocytes from undergoing ductular metaplasia.