Nuclear localization of hepatitis B core antigen and its relations to liver injury, hepatocyte proliferation, and viral load

Goals: The aim of this study was to determine the factor(s) independently affecting the HBcAg expression pattern in HBV-infected livers. Background: Subcellular localization of HBcAg have been found to be related to the activity of liver disease, hepatocyte proliferation rate and the level of HBV replication. Study: A total of 98 patients with biopsy proven chronic hepatitis B were included. HBcAg and proliferative cell nuclear antigen (PCNA) were immunohistochemically detected. HBcAg expression and its relationship with histologic activity index, ALT levels, PCNA score and HBV DNA levels were investigated. Results: Forty-three (44%) patients were positive for HBcAg staining, with most of them (37 patients) having nuclear localization. Forty-seven percent of patients with detectable HBV DNA had nuclear staining while none of the HBV DNA negative patients had nuclear staining (P < 0.0005). Patients with positive nuclear staining had lower HAI (<8) and a lower PCNA score (<353/1,000 cell) than those with negative staining (62% vs. 39% and 90% vs. 66%, respectively, P < 0.05). In multivariate analysis, both high HBV DNA level and low HAI (P < 0.0005 and P < 0.05, respectively) but not PCNA score, were independently associated with nuclear staining of HBcAg. Conclusions: Our results suggest that viral load and the severity of liver damage but not the rate of hepatocyte proliferation independently affects the HBcAg expression pattern.