Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1982 Dec;79(23):7522–7526. doi: 10.1073/pnas.79.23.7522

Hepatitis B viral DNA in liver and serum of asymptomatic carriers.

W Kam, L B Rall, E A Smuckler, R Schmid, W J Rutter
PMCID: PMC347372  PMID: 6961428

Abstract

Cloned DNA probes were used to test for hepatitis B virus (HBV) DNA in the liver and serum of 14 asymptomatic hepatitis B surface antigen (HBsAg) carriers and two former carriers. The results were compared with serological markers of HBV infection and liver histopathology. Three groups of carriers were distinguished. In group I, HBV DNA was present in both liver and serum. Hepatitis B e antigen (HBeAg), a marker of viral replication, was uniformly positive in serum. In one individual in this group, viral DNA was also integrated into liver genomic DNA. In group II, lower levels of nonintegrated HBV DNA were detected in the liver, but no HBV DNA was found in the serum. HBeAg was negative and with one exception there were antibodies to HBeAg. Integrated viral DNA was present in each case. In group III, there was no detectable nonintegrated viral DNA in serum or liver, but one individual had integrated sequences. All carriers lacked antibodies to HBsAg and had antibodies to hepatitis B core antigen and demonstrated nonspecific histological abnormalities in the liver. These findings indicate significant quantitative and qualitative differences among asymptomatic HBsAg carriers and suggest that their infectivity may be highly variable.

Full text

PDF
7525

Images in this article

Selected References

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

  1. Acute and chronic hepatitis revisited. Review by an international group. Lancet. 1977 Oct 29;2(8044):914–919. [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. Brechot C., Hadchouel M., Scotto J., Degos F., Charnay P., Trepo C., Tiollais P. Detection of hepatitis B virus DNA in liver and serum: a direct appraisal of the chronic carrier state. Lancet. 1981 Oct 10;2(8250):765–768. doi: 10.1016/s0140-6736(81)90182-3. [DOI] [PubMed] [Google Scholar]
  4. Bréchot C., Hadchouel M., Scotto J., Fonck M., Potet F., Vyas G. N., Tiollais P. State of hepatitis B virus DNA in hepatocytes of patients with hepatitis B surface antigen-positive and -negative liver diseases. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3906–3910. doi: 10.1073/pnas.78.6.3906. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chakraborty P. R., Ruiz-Opazo N., Shouval D., Shafritz D. A. Identification of integrated hepatitis B virus DNA and expression of viral RNA in an HBsAg-producing human hepatocellular carcinoma cell line. Nature. 1980 Jul 31;286(5772):531–533. doi: 10.1038/286531a0. [DOI] [PubMed] [Google Scholar]
  6. Charnay P., Pourcel C., Louise A., Fritsch A., Tiollais P. Cloning in Escherichia coli and physical structure of hepatitis B virion DNA. Proc Natl Acad Sci U S A. 1979 May;76(5):2222–2226. doi: 10.1073/pnas.76.5.2222. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. De Groote J., Fevery J., Lepoutre L. Long-term follow-up of chronic active hepatitis of moderate severity. Gut. 1978 Jun;19(6):510–513. doi: 10.1136/gut.19.6.510. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Edman J. C., Gray P., Valenzuela P., Rall L. B., Rutter W. J. Integration of hepatitis B virus sequences and their expression in a human hepatoma cell. Nature. 1980 Jul 31;286(5772):535–538. doi: 10.1038/286535a0. [DOI] [PubMed] [Google Scholar]
  9. Ganem D. Persistent infection of humans with hepatitis B virus: mechanisms and consequences. Rev Infect Dis. 1982 Sep-Oct;4(5):1026–1047. doi: 10.1093/clinids/4.5.1026. [DOI] [PubMed] [Google Scholar]
  10. Kafatos F. C., Jones C. W., Efstratiadis A. Determination of nucleic acid sequence homologies and relative concentrations by a dot hybridization procedure. Nucleic Acids Res. 1979 Nov 24;7(6):1541–1552. doi: 10.1093/nar/7.6.1541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Maugh T. H., 2nd Hepatitis B vaccine passes first major test. Science. 1980 Nov 14;210(4471):760–762. doi: 10.1126/science.6254146. [DOI] [PubMed] [Google Scholar]
  12. Pasek M., Goto T., Gilbert W., Zink B., Schaller H., MacKay P., Leadbetter G., Murray K. Hepatitis B virus genes and their expression in E. coli. Nature. 1979 Dec 6;282(5739):575–579. doi: 10.1038/282575a0. [DOI] [PubMed] [Google Scholar]
  13. Ricci G., De Bac C., Caramia F. Carriers of hepatitis B antigen: an epidemiologic and histologic study. J Infect Dis. 1973 Jul;128(1):125–128. doi: 10.1093/infdis/128.1.125. [DOI] [PubMed] [Google Scholar]
  14. Sakuma K., Takahara T., Okuda K., Tsuda F., Mayumi M. Prognosis of hepatitis B virus surface antigen carriers in relation to routine liver function tests: a prospective study. Gastroenterology. 1982 Jul;83(1 Pt 1):114–117. [PubMed] [Google Scholar]
  15. Sampliner R. E., Hamilton F. A., Iseri O. A., Tabor E., Boitnott J. The liver histology and frequency of clearance of the hepatitis B surface antigen (HBsAg) in chronic carriers. Am J Med Sci. 1979 Jan-Feb;277(1):17–22. doi: 10.1097/00000441-197901000-00002. [DOI] [PubMed] [Google Scholar]
  16. Scullard G. H., Andres L. L., Greenberg H. B., Smith J. L., Sawhney V. K., Neal E. A., Mahal A. S., Popper H., Merigan T. C., Robinson W. S. Antiviral treatment of chronic hepatitis B virus infection: improvement in liver disease with interferon and adenine arabinoside. Hepatology. 1981 May-Jun;1(3):228–232. doi: 10.1002/hep.1840010306. [DOI] [PubMed] [Google Scholar]
  17. Shafritz D. A., Kew M. C. Identification of integrated hepatitis B virus DNA sequences in human hepatocellular carcinomas. Hepatology. 1981 Jan-Feb;1(1):1–8. doi: 10.1002/hep.1840010102. [DOI] [PubMed] [Google Scholar]
  18. Shafritz D. A., Shouval D., Sherman H. I., Hadziyannis S. J., Kew M. C. Integration of hepatitis B virus DNA into the genome of liver cells in chronic liver disease and hepatocellular carcinoma. Studies in percutaneous liver biopsies and post-mortem tissue specimens. N Engl J Med. 1981 Oct 29;305(18):1067–1073. doi: 10.1056/NEJM198110293051807. [DOI] [PubMed] [Google Scholar]
  19. Shikata T., Karasawa T., Abe K., Uzawa T., Suzuki H., Oda T., Imai M., Mayumi M., Moritsugu Y. Hepatitis B e antigen and infectivity of hepatitis B virus. J Infect Dis. 1977 Oct;136(4):571–576. doi: 10.1093/infdis/136.4.571. [DOI] [PubMed] [Google Scholar]
  20. Siddiqui A., Sattler F., Robinson W. S. Restriction endonuclease cleavage map and location of unique features of the DNA of hepatitis B virus, subtype adw2. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4664–4668. doi: 10.1073/pnas.76.9.4664. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  22. Valenzuela P., Gray P., Quiroga M., Zaldivar J., Goodman H. M., Rutter W. J. Nucleotide sequence of the gene coding for the major protein of hepatitis B virus surface antigen. Nature. 1979 Aug 30;280(5725):815–819. doi: 10.1038/280815a0. [DOI] [PubMed] [Google Scholar]
  23. Wu P. C., Lam K. C. Cytoplasmic hepatitis B surface antigen and the ground-glass appearance in hepatocellular carcinoma. Am J Clin Pathol. 1979 Feb;71(2):229–234. doi: 10.1093/ajcp/71.2.229. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES