SUBCELLULAR-LOCALIZATION OF HEPATITIS-B CORE ANTIGEN IN RELATION TO HEPATOCYTE REGENERATION IN CHRONIC HEPATITIS-B

Background & Aims: To test whether the dominant cytoplasmic expression of hepatitis B core antigen (HBcAg) in active chronic hepatitis B is secondary to liver damage and regeneration, the relationship between s ubcellular localization of HBcAg, liver inflammatory activity, and hep atocyte regeneration in chronic hepatitis B was studied. Methods: Corr elation of the clinical and laboratory data with the topographical dis tribution of HBcAg was studied in 30 patients. The subcellular localiz ation of HBcAg in relation to hepatocyte cell cycles was studied by do uble immunostaining of HBcAg and proliferating cell nuclear antigen. R esults: Patients with predominant cytoplasmic HBcAg had significantly higher levels of biochemical and histological activities and prolifera ting cell nuclear antigen expression than patients with predominant nu clear HBcAg. The levels of proliferating cell nuclear antigen expressi on correlated positively with biochemical and histological activities and degrees of cytoplasmic HBcAg expression but negatively with degree s of nuclear HBcAg expression. Proliferating cell nuclear antigen expr ession was shown in 49% of hepatocytes with cytoplasmic HBcAg but in o nly 2% of hepatocytes with nuclear HBcAg. Conclusions: These findings suggested that, following liver damage, the regeneration of surviving hepatocytes might cause the shift of intracellular HBcAg from nucleus to cytoplasm. As a result, the extent of nuclear HBcAg expression redu ces with concomitant increase in cytoplasmic HBcAg expression.