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. 1995 May;48(5):470–473. doi: 10.1136/jcp.48.5.470

Membrane staining for hepatitis B surface antigen on hepatocytes: a sensitive and specific marker of active viral replication in hepatitis B.

C M Chu 1, Y F Liaw 1
PMCID: PMC502627  PMID: 7629296

Abstract

AIMS--To test the hypothesis that membranous staining of hepatitis B surface antigen (HBsAg) on the hepatocyte is a marker of active viral replication in chronic hepatitis B virus (HBV) infection. METHODS--Intrahepatic expression of HBsAg and hepatitis B core antigen (HBcAg) was studied by indirect immunofluorescence on frozen sections of liver specimens from 75 patients with chronic hepatitis B, and the results were correlated with serum levels of HBV-DNA assayed by spot hybridisation. RESULTS--Hepatocyte HBcAg was detected in all of 20 patients with serum levels of HBV-DNA > 1000 pg/ml, 18 (75%) of 24 patients with levels of HBV-DNA < or = 1000 pg/ml, and two (6.5%) of 31 patients without detectable serum HBV-DNA. The concordance between hepatocyte HBcAg and serum HBV-DNA was 89.3% (67/75). There were six patients (8%) who had detectable serum HBV-DNA but without hepatocyte HBcAg, and two patients (2.7%) who had detectable hepatocyte HBcAg but without serum HBV-DNA. Membranous staining of HBsAg associated with variable degrees of cytoplasmic HBsAg was found in all but one of 44 patients with serum HBV-DNA, irrespective of the levels, but in none of the 31 patients without serum HBV-DNA. Of the latter, HBsAg was distributed solely in the cytoplasm. In addition, there is an inverse correlation between serum levels of HBV-DNA and the degrees of cytoplasmic staining of HBsAg. The concordance between membranous staining fo HBsAg and serum HBV-DNA was 98.7% (74/75), significantly higher than that between hepatocyte HBcAG and serum HBV-DNA. CONCLUSIONS--Membranous staining of HBsAg on the hepatocyte correlated excellently with serum HBV-DNA and thus can be recognised as a sensitive and specific marker of active hepatitis B virus replication.

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Selected References

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  1. Berninger M., Hammer M., Hoyer B., Gerin J. L. An assay for the detection of the DNA genome of hepatitis B virus in serum. J Med Virol. 1982;9(1):57–68. doi: 10.1002/jmv.1890090109. [DOI] [PubMed] [Google Scholar]
  2. Bonino F., Hoyer B., Nelson J., Engle R., Verme G., Gerin J. Hepatitis B virus DNA in the sera of HBsAg carriers: a marker of active hepatitis B virus replication in the liver. Hepatology. 1981 Sep-Oct;1(5):386–391. doi: 10.1002/hep.1840010503. [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. Immunohistological study of intrahepatic expression of hepatitis B core and E antigens in chronic type B hepatitis. J Clin Pathol. 1992 Sep;45(9):791–795. doi: 10.1136/jcp.45.9.791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. Freiman J., Eckstein R., McCaughan G., Parsons C., Davies J. S., Diegutis P., Burnett L., Gallagher N. Significance of serum and hepatic markers of hepatitis B viral infection in HBsAg-positive and HBsAg-negative chronic active hepatitis. Hepatology. 1985 Jan-Feb;5(1):50–53. doi: 10.1002/hep.1840050112. [DOI] [PubMed] [Google Scholar]
  7. Goodman Z. D., Langloss J. M., Bratthauer G. L., Ishak K. Immunohistochemical localization of hepatitis B surface antigen and hepatitis B core antigen in tissue sections. A source of false positive staining. Am J Clin Pathol. 1988 Apr;89(4):533–537. doi: 10.1093/ajcp/89.4.533. [DOI] [PubMed] [Google Scholar]
  8. Gowans E. J., Burrell C. J. Widespread presence of cytoplasmic HBcAg in hepatitis B infected liver detected by improved immunochemical methods. J Clin Pathol. 1985 Apr;38(4):393–398. doi: 10.1136/jcp.38.4.393. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. Hadziyannis S. J., Lieberman H. M., Karvountzis G. G., Shafritz D. A. Analysis of liver disease, nuclear HBcAg, viral replication, and hepatitis B virus DNA in liver and serum of HBeAg Vs. anti-HBe positive carriers of hepatitis B virus. Hepatology. 1983 Sep-Oct;3(5):656–662. doi: 10.1002/hep.1840030505. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. 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]
  13. Kakumu S., Arao M., Yoshioka K., Tsutsumi Y., Inoue M. Distribution of HBcAg in hepatitis B detected by immunoperoxidase staining with three different preparations of anti-HBc antibodies. J Clin Pathol. 1989 Mar;42(3):284–288. doi: 10.1136/jcp.42.3.284. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Karayiannis P., Fowler M. J., Lok A. S., Greenfield C., Monjardino J., Thomas H. C. Detection of serum HBV-DNA by molecular hybridisation. Correlation with HBeAg/anti-HBe status, racial origin, liver histology and hepatocellular carcinoma. J Hepatol. 1985;1(2):99–106. doi: 10.1016/s0168-8278(85)80759-5. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. 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]
  17. 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]
  18. Thung S. N., Gerber M. A. Hepatitis B virus and polyalbumin binding sites. Gastroenterology. 1983 Aug;85(2):466–468. [PubMed] [Google Scholar]
  19. Weller I. V., Fowler M. J., Monjardino J., Thomas H. C. The detection of HBV-DNA in serum by molecular hybridisation: a more sensitive method for the detection of complete HBV particles. J Med Virol. 1982;9(4):273–280. doi: 10.1002/jmv.1890090405. [DOI] [PubMed] [Google Scholar]
  20. Wu J. C., Lee S. D., Wang J. Y., Ting L. P., Tsai Y. T., Tsay S. H., Tong M. J. Correlation between hepatic hepatitis B core antigen and serum hepatitis B virus-DNA levels in patients with chronic hepatitis B virus infections in Taiwan. Arch Pathol Lab Med. 1987 Feb;111(2):181–184. [PubMed] [Google Scholar]
  21. 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]
  22. Yoo J. Y., Howard R., Waggoner J. G., Hoofnagle J. H. Peroxidase-anti-peroxidase detection of hepatitis B surface and core antigen in liver biopsy specimens from patients with chronic type B hepatitis. J Med Virol. 1987 Nov;23(3):273–281. doi: 10.1002/jmv.1890230310. [DOI] [PubMed] [Google Scholar]

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