Hepatocyte regeneration in hepatitis B virus-related chronic liver disease revealed by proliferating cell nuclear antigen

Proliferating cell nuclear antigen (PCNA) is a nuclear protein synthesised in G 1/S-phase of the cell cycle, which can be demonstrated immunohistochemically on paraffin-embedded tissue sections as an indicator of proliferative activity of the tissues. This study aims to investigate the proliferation rate of hepatocytes in HBV-related chronic liver disease (HBV-RCLD) and to find out whether this rate correlates with morphological findings of hepatocyte regeneration. Liver biopsy specimens of 60 cases with HBV-RCLD, including 20 cases of chronic hepatitis B (CHB), 20 cases of cirrhosis of the liver CHB (CL-CHB) and 20 cases of hepatocellular carcinoma associated with CL-CHB (HCC-CL) were examined for histopathologic findings of regeneration and PCNA immunoreactivity. Mean PCNA scores were in the following order; HCC-CL (tumour tissue)> HCC-CL (cirrhotic tissue)> CHB> CL-CHB. In HCC-CL, PCNA scores of both tumour and cirrhotic tissues were significantly higher than in the other groups. Multinucleation and liver-cell rosettes (LCRs) were significantly higher in CL-CHB and HCC-CL; whereas nuclear polymorphism was significantly higher in HCC-CL. In CHB multinucleation showed correlation with high PCNA scores. Nuclear polymorphism and LCRs were associated with high PCNA scores irrespective of the diagnoses. These data suggest that the PCNA scores may be helpful in the follow-up of patients with HBV-RCLD.