Immunohistochemical study of ductular proliferation in patients with hepatitis B virus induced end-stage chronic liver disease

【Objective】Ductular proliferation is frequently observed in the liver tissue sections of patients with end-stage chronic liver disease induced by hepatitis B virus (HBV), but its pathogenesis and significance remain unclear. In order to clarify the pathogenesis of ductular proliferation and its possible association with oval cell activation and hepatocyte regeneration, we performed immunohistochemical staining and image analysis of the ductular structures in the liver tissues from 8 patients with HBV-induced end-stage chronic liver disease and 2 healthy individuals. 【Methods】 The liver specimens were sectioned serially, and then cytokeratin (CK) 7, CK8, CK19, OV6, proliferating cell nuclear antigens (PCNA), α-fetal protein (AFP) and albumin (ALB) were stained immunohistochemically. 【Results】 Typical type and atypical type of ductular proliferation were observed in the portal tracts of the liver tissues in all 8 patients. The proliferating ductular cells were positive for CK7, CK8, CK19, OV6 and PCNA staining, however, typical proliferating ductular cells differed significantly from atypical ones in the intensity and extent of staining. Some atypical ductular cells displayed the morphological and immunohistochemical characteristics of hepatic oval cells. Some small hepatocyte-like cells were between hepatic oval cells and mature hepatocytes morphometrically and immunohistochemically. 【Conclusions】 It is concluded that the proliferating ductules in the liver of patients with HBV-related end-stage chronic liver disease may have different origins. Some atypical ductular cells are actually activated hepatic oval cells. Atypical ductular proliferation is related to hepatocyte regeneration and small hepatocyte-like cells may be intermediate transient cells between hepatic oval cells and mature heptocytes.