Skip to main content
PMC home page
Journal of Clinical Pathology logoLink to Journal of Clinical Pathology
. 1992 Sep;45(9):791–795. doi: 10.1136/jcp.45.9.791

Immunohistological study of intrahepatic expression of hepatitis B core and E antigens in chronic type B hepatitis.

C M Chu 1, Y F Liaw 1
PMCID: PMC495106  PMID: 1401209

Abstract

AIMS: To study the intrahepatic expression of hepatitis B virus (HBV) nucleocapsid antigen; and to determine the differential distribution of hepatitis B core and E antigens in chronic hepatitis B. METHODS: Hepatocyte expression of HBV nucleocapsid antigen was studied using rabbit anti-HBc, directed against both HBcAg and HBeAg; differential distribution of HBcAg and HBeAg was studied using murine monoclonal anti-HBc and anti-HBe in 120 patients with chronic hepatitis B. RESULTS: HBV nucleocapsid antigen was detected in 14 of 16 (87.5%) HBeAg seropositive patients with chronic persistent hepatitis (CPH), and in 54 of 64 (84.4%) HBeAg seropositive patients with chronic active hepatitis (CAH). Nuclear expression of nucleocapsid antigen was more prevalent in patients with CPH than in those with CAH; this was reversed in terms of exclusive cytoplasmic expression of nucleocapsid antigen (p < 0.05). Of 45 patients with nucleocapsid antigen in the nucleus, samples from 44 (97.8%) and 17 (37.8%) stained positively with monoclonal anti-HBc and anti-HBe, respectively. Of 65 patients with cytoplasmic nucleocapsid antigen, samples from 61 (93.8%) and 57 (87.7%) stained positively with monoclonal anti-HBc and anti-HBe, respectively. CONCLUSIONS: HBV nucleocapsid antigen is more prevalent in HBeAg positive patients with CPH than in those with CAH. Cellular expression of HBcAg and HBeAg in the cytoplasm is more or less the same; in the nucleus HBcAg exceeds HBeAg expression.

Full text

PDF

Images in this article

792Image
on p.792
792Image
on p.792

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ballaré M., Lavarini C., Brunetto M. R., Petruzzelli E., Dovis M., Molino G., Bonino F. Relationship between the intrahepatic expression of 'e' and 'c' epitopes of the nucleocapsid protein of hepatitis B virus and viraemia. Clin Exp Immunol. 1989 Jan;75(1):64–69. [PMC free article] [PubMed] [Google Scholar]
  2. Carman W. F., Jacyna M. R., Hadziyannis S., Karayiannis P., McGarvey M. J., Makris A., Thomas H. C. Mutation preventing formation of hepatitis B e antigen in patients with chronic hepatitis B infection. Lancet. 1989 Sep 9;2(8663):588–591. doi: 10.1016/s0140-6736(89)90713-7. [DOI] [PubMed] [Google Scholar]
  3. Chu C. M., Karayiannis P., Fowler M. J., Monjardino J., Liaw Y. F., Thomas H. C. Natural history of chronic hepatitis B virus infection in Taiwan: studies of hepatitis B virus DNA in serum. Hepatology. 1985 May-Jun;5(3):431–434. doi: 10.1002/hep.1840050315. [DOI] [PubMed] [Google Scholar]
  4. Chu C. M., Liaw Y. F. Intrahepatic distribution of hepatitis B surface and core antigens in chronic hepatitis B virus infection. Hepatocyte with cytoplasmic/membranous hepatitis B core antigen as a possible target for immune hepatocytolysis. Gastroenterology. 1987 Jan;92(1):220–225. doi: 10.1016/0016-5085(87)90863-8. [DOI] [PubMed] [Google Scholar]
  5. Chu C. M., Liaw Y. F. Intrahepatic expression of HBcAg in chronic HBV hepatitis: lessons from molecular biology. Hepatology. 1990 Dec;12(6):1443–1445. doi: 10.1002/hep.1840120630. [DOI] [PubMed] [Google Scholar]
  6. Ferns R. B., Tedder R. S. Monoclonal antibodies to hepatitis Be antigen (HBeAg) derived from hepatitis B core antigen (HBcAg): their use in characterization and detection of HBeAg. J Gen Virol. 1984 May;65(Pt 5):899–908. doi: 10.1099/0022-1317-65-5-899. [DOI] [PubMed] [Google Scholar]
  7. Gerber M. A., Sells M. A., Chen M. L., Thung S. N., Tabibzadeh S. S., Hood A., Acs G. Morphologic, immunohistochemical, and ultrastructural studies of the production of hepatitis B virus in vitro. Lab Invest. 1988 Aug;59(2):173–180. [PubMed] [Google Scholar]
  8. Gudat F., Bianchi L., Sonnabend W., Thiel G., Aenishaenslin W., Stalder G. A. Pattern of core and surface expression in liver tissue reflects state of specific immune response in hepatitis B. Lab Invest. 1975 Jan;32(1):1–9. [PubMed] [Google Scholar]
  9. Hsu H. C., Su I. J., Lai M. Y., Chen D. S., Chang M. H., Chuang S. M., Sung J. L. Biologic and prognostic significance of hepatocyte hepatitis B core antigen expressions in the natural course of chronic hepatitis B virus infection. J Hepatol. 1987 Aug;5(1):45–50. doi: 10.1016/s0168-8278(87)80060-0. [DOI] [PubMed] [Google Scholar]
  10. Huang S. N., Neurath A. R. Immunohistologic demonstration of hepatitis B viral antigens in liver with reference to its significance in liver injury. Lab Invest. 1979 Jan;40(1):1–17. [PubMed] [Google Scholar]
  11. Kaneko S., Miller R. H., Di Bisceglie A. M., Feinstone S. M., Hoofnagle J. H., Purcell R. H. Detection of hepatitis B virus DNA in serum by polymerase chain reaction. Application for clinical diagnosis. Gastroenterology. 1990 Sep;99(3):799–804. doi: 10.1016/0016-5085(90)90971-3. [DOI] [PubMed] [Google Scholar]
  12. Kojima T., Bloemen J., Desmet V. J. Immune electron microscopic demonstration of hepatitis B core antigen (HBcAg) in liver cell plasma membranes. Liver. 1987 Aug;7(4):191–200. doi: 10.1111/j.1600-0676.1987.tb00342.x. [DOI] [PubMed] [Google Scholar]
  13. Lai K. N., Lai F. M., Tam J. S. Comparison of polyclonal and monoclonal antibodies in determination of glomerular deposits of hepatitis B virus antigens in hepatitis B virus-associated glomerulonephritides. Am J Clin Pathol. 1989 Aug;92(2):159–165. doi: 10.1093/ajcp/92.2.159. [DOI] [PubMed] [Google Scholar]
  14. Mondelli M., Tedder R. S., Ferns B., Pontisso P., Realdi G., Alberti A. Differential distribution of hepatitis B core and E antigens in hepatocytes: analysis by monoclonal antibodies. Hepatology. 1986 Mar-Apr;6(2):199–204. doi: 10.1002/hep.1840060208. [DOI] [PubMed] [Google Scholar]
  15. Mondelli M., Vergani G. M., Alberti A., Vergani D., Portmann B., Eddleston A. L., Williams R. Specificity of T lymphocyte cytotoxicity to autologous hepatocytes in chronic hepatitis B virus infection: evidence that T cells are directed against HBV core antigen expressed on hepatocytes. J Immunol. 1982 Dec;129(6):2773–2778. [PubMed] [Google Scholar]
  16. Montano L., Miescher G. C., Goodall A. H., Wiedmann K. H., Janossy G., Thomas H. C. Hepatitis B virus and HLA antigen display in the liver during chronic hepatitis B virus infection. Hepatology. 1982 Sep-Oct;2(5):557–561. doi: 10.1002/hep.1840020508. [DOI] [PubMed] [Google Scholar]
  17. Ou J. H., Yeh C. T., Yen T. S. Transport of hepatitis B virus precore protein into the nucleus after cleavage of its signal peptide. J Virol. 1989 Dec;63(12):5238–5243. doi: 10.1128/jvi.63.12.5238-5243.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Pignatelli M., Waters J., Lever A., Iwarson S., Gerety R., Thomas H. C. Cytotoxic T-cell responses to the nucleocapsid proteins of HBV in chronic hepatitis. Evidence that antibody modulation may cause protracted infection. J Hepatol. 1987 Feb;4(1):15–21. doi: 10.1016/s0168-8278(87)80004-1. [DOI] [PubMed] [Google Scholar]
  19. Ray M. B., Desmet V. J., Bradburne A. F., Desmyter J., Fevery J., De Groote J. Differential distribution of hepatitis B surface antigen and hepatitis B core antigen in the liver of hepatitis B patients. Gastroenterology. 1976 Sep;71(3):462–469. [PubMed] [Google Scholar]
  20. Takahashi K., Akahane Y., Gotanda T., Mishiro T., Imai M., Miyakawa Y., Mayumi M. Demonstration of hepatitis B e antigen in the core of Dane particles. J Immunol. 1979 Jan;122(1):275–279. [PubMed] [Google Scholar]
  21. Takahashi K., Machida A., Funatsu G., Nomura M., Usuda S., Aoyagi S., Tachibana K., Miyamoto H., Imai M., Nakamura T. Immunochemical structure of hepatitis B e antigen in the serum. J Immunol. 1983 Jun;130(6):2903–2907. [PubMed] [Google Scholar]
  22. Tiollais P., Pourcel C., Dejean A. The hepatitis B virus. Nature. 1985 Oct 10;317(6037):489–495. doi: 10.1038/317489a0. [DOI] [PubMed] [Google Scholar]
  23. Tsai S. L., Chen P. J., Lai M. Y., Yang P. M., Sung J. L., Huang J. H., Hwang L. H., Chang T. H., Chen D. S. Acute exacerbations of chronic type B hepatitis are accompanied by increased T cell responses to hepatitis B core and e antigens. Implications for hepatitis B e antigen seroconversion. J Clin Invest. 1992 Jan;89(1):87–96. doi: 10.1172/JCI115590. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Yamada G., Nakane P. K. Hepatitis B core and surface antigens in liver tissue. Light and electron microscopic localization by the peroxidase-labeled antibody method. Lab Invest. 1977 Jun;36(6):649–659. [PubMed] [Google Scholar]
  25. Yamada G., Takaguchi K., Matsueda K., Nishimoto H., Takahashi M., Fujiki S., Mizuno M., Kinoyama S., Tsuji T. Immunoelectron microscopic observation of intrahepatic HBeAg in patients with chronic hepatitis B. Hepatology. 1990 Jul;12(1):133–140. doi: 10.1002/hep.1840120121. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Pathology are provided here courtesy of BMJ Publishing Group

RESOURCES