Immunopathology on hepatocyte expression of HBV surface, core, and x antigens in chronic hepatitis B: clinical and virological correlation
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Updated: Jun 21, 2026

A Competent Hepatocyte Model Examining Hepatitis B Virus Entry through Sodium Taurocholate Cotransporting Polypeptide as a Therapeutic Target
Published on: May 10, 2022
Chia-Ming Chu1, Wei-Chue Shyu, Yun-Fan Liaw
1Liver Research Unit, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 199 Tung Hwa North Road, Taipei 10591, Taiwan. chiamingchu@yahoo.com.tw
Purpose:
Hepatocyte expression of HBV surface, core, and x antigens (HBsAg, HBcAg and HBxAg), semi-quantitated by immunopathology, were correlated with clinical and virological data in 80 patients with chronic hepatitis B.
Results:
Seventy patients were HBsAg positive in cytoplasm, 61 were HBcAg positive, including 45 in both nucleus and cytoplasm and 16 in cytoplasm only, and 47 were HBxAg positive in cytoplasm. The detection rates for HBcAg increased while those for HBsAg and HBxAg decreased with HBV DNA levels. Positive HBcAg staining usually suggested the presence of HBV DNA levels >10(6) copies/ml. HBcAg, HBsAg, and HBxAg expressions showed no significant differences between patients with genotype B and C. Serum HBeAg and HBV DNA levels correlated positively with nuclear or cytoplasmic HBcAg expression but inversely with HBsAg expression. By multiple regression analysis, HBV DNA levels correlated significantly only with nuclear HBcAg expression. ALT levels and inflammatory grades correlated with cytoplasmic HBcAg expression. There was an inverse quantitative relationship between HBcAg and HBsAg expression. Furthermore, HBxAg expression correlated significantly with HBsAg expression as well as male gender.
Conclusions:
With diminishing HBV DNA levels following HBeAg seroconversion, HBcAg expression decreased but HBsAg expression increased with a concomitant increase in HBxAg expression. Whether the finding that a significantly higher expression of HBxAg observed in males than females may account for the gender difference in long-term sequelae of chronic HBV infection needs further investigation.
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