The role of precore and core promoter mutations in the pathogenesis of chronic hepatitis B is still not clear. Hepatitis B virus (HBV) in general is not cytopathic. Liver damage is supposed to be caused by immune response against viral antigens. Studies have shown that nuclear hepatitis B core antigen (HBcAg) and cytoplasmic hepatitis B e antigen (HBeAg) are associated with high level of HBV replication.1 Cytoplasmic HBcAg, rather than cytoplasmic HBeAg, is associated with active liver disease.1, 2
The precore sequence is believed to be essential for the nuclear translocation of HBcAg.3 Precore mutations by blocking the synthesis of HBeAg may prevent nuclear translocation of HBcAg. The cytoplasmic prominent (CP) expression of HBcAg is found in a majority of patients with precore mutations in recent studies.4–6 Core promoter mutations also decrease the synthesis of HBeAg.7 Their association with cytoplasmic expression of HBcAg has not been described. Precore and core promoter mutations often co-exist in patients with chronic hepatitis B.8,9 The association of precore mutations and core promoter mutations may further complicate the intrahepatic expression of HBcAg.
This study was performed to determine the relationship of precore and core promoter mutations, intrahepatic HBV DNA levels, intrahepatic expression of HBcAg/HBeAg and liver histology.