Correlation of hepatitis B core antigen and beta-catenin expression on hepatocytes in chronic hepatitis B virus infection: relevance to the severity of liver damage and viral replication

BACKGROUND AND AIMS: The topographical distribution of hepatitis B core antigen (HBcAg) is related to the pathogenesis of liver damage caused by hepatitis B virus (HBV) infection. beta-catenin plays an important role in both intracellular adhesion and Wnt signaling transduction pathways. This study investigated the intrahepatic expression of HBcAg and beta-catenin in chronic HBV infection, and correlated the results with the degree of liver damage and viral replication. METHOD: Liver sections from 73 patients with chronic HBV infection were examined immunohistochemically for HBcAg and beta-catenin. RESULTS: The distribution of HBcAg could be classified into four types: only nucleus (C-1), both nucleus and cytoplasm (C-2), only cytoplasm (C-3) and all negative for nucleus and cytoplasm (C-4). Significant differences in serum aminotransferase level, HBV DNA and necroinflammatory score were observed among the different distribution types, and as the distribution of HBcAg changed from C-1 to C-4, fibrosis stage and hepatitis B e antigen (HBeAg) negative/anti-HBe positive rate increased concurrently. The distribution of beta-catenin could be classified into two types: only membrane (B-1) and membrane with nucleus or cytoplasm (B-2). B-2 showed higher serum aminotransferase level and necroinflammatory score than B-1. Between B-1 and B-2, there was no significant difference in serum HBV DNA level or fibrosis stage. CONCLUSIONS: In chronic HBV infection, HBcAg distribution may change from C-1 to C-4 gradually, and in correlation with serum aminotransferase, and HBV DNA and HBeAg negative/anti-HBe positive rate. Nuclear or cytoplasmic distribution of beta-catenin, compared with exclusive membranous distribution of beta-catenin, is related to active hepatitis, but not viral replication.