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. 1970;42(6):957–992.

Viral hepatitis and tests for the Australia (hepatitis-associated) antigen and antibody*

PMCID: PMC2427559  PMID: 4991606

Abstract

”Australia” antigen has been shown to be closely associated with serum hepatitis. The presence of the antigen and its corresponding antiserum can be detected in human beings (and in certain primates) by a number of laboratory tests. This is of great potential importance to blood transfusion and similar services because detection and exclusion of blood donors carrying the antigen might significantly reduce the risk of hepatitis from transfusions and other procedures.

In this paper the present state of knowledge of ”Australia” or ”hepatitis-associated” antigen is reviewed. The currently employed tests are described in detail and their use, interpretation and limitations are discussed. Though it appears from early studies that the application of routine screening tests to blood donors would only reduce the risk to recipients by less than 25%, the more sensitive tests becoming available may increase this percentage and it is recommended that where competent laboratory services are available steps should be taken to set up a scheme for testing donors—provided that the current limitations of such a scheme are clearly recognized.

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Selected References

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

  1. ALLISON A. C., BLUMBERG B. S. An isoprecipitation reaction distinguishing human serum-protein types. Lancet. 1961 Mar 25;1(7178):634–637. doi: 10.1016/s0140-6736(61)91654-3. [DOI] [PubMed] [Google Scholar]
  2. ASTER R. H., JANDL J. H. PLATELET SEQUESTRATION IN MAN. I. METHODS. J Clin Invest. 1964 May;43:843–855. doi: 10.1172/JCI104970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Almeida J. D., Waterson A. P. Immune complexes in hepatitis. Lancet. 1969 Nov 8;2(7628):983–986. doi: 10.1016/s0140-6736(69)90540-6. [DOI] [PubMed] [Google Scholar]
  4. Alter H. J., Blumberg B. S. Further studies on a "new" human isoprecipitin system (Australia antigen). Blood. 1966 Mar;27(3):297–309. [PubMed] [Google Scholar]
  5. BLUMBERG B. S., ALTER H. J., VISNICH S. A "NEW" ANTIGEN IN LEUKEMIA SERA. JAMA. 1965 Feb 15;191:541–546. doi: 10.1001/jama.1965.03080070025007. [DOI] [PubMed] [Google Scholar]
  6. BLUMBERG B. S., DRAY S., ROBINSON J. C. Antigen polymorphism of a low-density beta-lipoprotein. Allotypy in human serum. Nature. 1962 May 19;194:656–658. doi: 10.1038/194656a0. [DOI] [PubMed] [Google Scholar]
  7. BLUMBERG B. S. POLYMORPHISMS OF THE SERUM PROTEINS AND THE DEVELOPMENT OF ISO-PRECIPITINS IN TRANSFUSED PATIENTS. Bull N Y Acad Med. 1964 May;40:377–386. [PMC free article] [PubMed] [Google Scholar]
  8. BLUMBERG B. S., RIDDELL N. M. Inherited antigenic differences in human serum beta lipoproteins. A second antiserum. J Clin Invest. 1963 Jun;42:867–875. doi: 10.1172/JCI104779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. BRADSTREET C. M., TAYLOR C. E. Technique of complementfixation test applicable to the diagnosis of virus diseases. Mon Bull Minist Health Public Health Lab Serv. 1962 May;21:96–104. [PubMed] [Google Scholar]
  10. BRENNER S., HORNE R. W. A negative staining method for high resolution electron microscopy of viruses. Biochim Biophys Acta. 1959 Jul;34:103–110. doi: 10.1016/0006-3002(59)90237-9. [DOI] [PubMed] [Google Scholar]
  11. Bancroft J. B., Hiebert E., Bracker C. E. The effects of various polyanions on shell formation of some spherical viruses. Virology. 1969 Dec;39(4):924–930. doi: 10.1016/0042-6822(69)90029-4. [DOI] [PubMed] [Google Scholar]
  12. Barker L. F., Smith K. O., Gehle W. D., Shulman N. R. Some antigenic and physical properties of virus-like particles in sera of hepatitis patients. J Immunol. 1969 Jun;102(6):1529–1532. [PubMed] [Google Scholar]
  13. Bayer M. E., Blumberg B. S., Werner B. Particles associated with Australia antigen in the sera of patients with leukaemia, Down's Syndrome and hepatitis. Nature. 1968 Jun 15;218(5146):1057–1059. doi: 10.1038/2181057a0. [DOI] [PubMed] [Google Scholar]
  14. Blumberg B. S., Friedlaender J. S., Woodside A., Sutnick A. I., London W. T. Hepatitis and Australia antigen: autosomal recessive inheritance of susceptibility to infection in humans. Proc Natl Acad Sci U S A. 1969 Apr;62(4):1108–1115. doi: 10.1073/pnas.62.4.1108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Blumberg B. S., Gerstley B. J., Hungerford D. A., London W. T., Sutnick A. I. A serum antigen (Australia antigen) in Down's syndrome, leukemia, and hepatitis. Ann Intern Med. 1967 May;66(5):924–931. doi: 10.7326/0003-4819-66-5-924. [DOI] [PubMed] [Google Scholar]
  16. Blumberg B. S., Melartin L., Guint R. A., Werner B. Family studies of a human serum isoantigen system (Australia antigen). Am J Hum Genet. 1966 Nov;18(6):594–608. [PMC free article] [PubMed] [Google Scholar]
  17. Blumberg B. S., Sutnick A. I., London W. T. Australia antigen and hepatitis. JAMA. 1969 Mar 10;207(10):1895–1896. [PubMed] [Google Scholar]
  18. Blumberg B. S., Sutnick A. I., London W. T. Hepatitis and leukemia: their relation to Australia antigen. Bull N Y Acad Med. 1968 Dec;44(12):1566–1586. [PMC free article] [PubMed] [Google Scholar]
  19. CONRAD M. E., SCHWARTZ F. D., YOUND A. A. INFECTIOUS HEPATITIS; A GENERALIZED DISEASE. A STUDY OF RENAL, GASTROINTESTINAL AND HEMATOLOGIC ABNORMALITIES. Am J Med. 1964 Nov;37:789–801. doi: 10.1016/0002-9343(64)90027-0. [DOI] [PubMed] [Google Scholar]
  20. CURTAIN C. C. The chromatographic purification of fluorescein-antibody. J Histochem Cytochem. 1961 Sep;9:484–486. doi: 10.1177/9.5.484. [DOI] [PubMed] [Google Scholar]
  21. Cossart Y. E., Vahrman J. Studies of Australia-SH antigen in sporadic viral hepatitis in London. Br Med J. 1970 Feb 14;1(5693):403–405. doi: 10.1136/bmj.1.5693.403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Coyne V. E., Millman I., Cerda J., Gerstley B. J., London T., Sutnick A., Blumberg B. S. The localization of Australia antigen by immunofluorescence. J Exp Med. 1970 Feb;131(2):307–319. doi: 10.1084/jem.131.2.307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Dane D. S., Cameron C. H., Briggs M. Virus-like particles in serum of patients with Australia-antigen-associated hepatitis. Lancet. 1970 Apr 4;1(7649):695–698. doi: 10.1016/s0140-6736(70)90926-8. [DOI] [PubMed] [Google Scholar]
  24. Deinhardt F., Holmes A. W., Capps R. B., Popper H. Studies on the transmission of human viral hepatitis to marmoset monkeys. I. Transmission of disease, serial passages, and description of liver lesions. J Exp Med. 1967 Apr 1;125(4):673–688. doi: 10.1084/jem.125.4.673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Feizi T., Gitlin N. Immune-complex disease of the kidney associated with chronic hepatitis and cryoglobulinaemia. Lancet. 1969 Oct 25;2(7626):873–876. doi: 10.1016/s0140-6736(69)92329-0. [DOI] [PubMed] [Google Scholar]
  26. GERLOFF R. K., HOYER B. H., McLAREN L. C. Precipitation of radiolabeled poliovirus with specific antibody and antiglobulin. J Immunol. 1962 Oct;89:559–570. [PubMed] [Google Scholar]
  27. Gerin J. L., Purcell R. H., Hoggan M. D., Holland P. V., Chanock R. M. Biophysical properties of Australia antigen. J Virol. 1969 Nov;4(5):763–768. doi: 10.1128/jvi.4.5.763-768.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Gerin J. L., Purcell R. H., Hoggan M. D., Holland P. V., Chanock R. M. Biophysical properties of Australia antigen. J Virol. 1969 Nov;4(5):763–768. doi: 10.1128/jvi.4.5.763-768.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Giles J. P., McCollum R. W., Berndtson L. W., Jr, Krugman S. Relation of Australia-SH antigen to the willowbrook MS-2 strain. N Engl J Med. 1969 Jul 17;281(3):119–122. doi: 10.1056/NEJM196907172810302. [DOI] [PubMed] [Google Scholar]
  30. Gocke D. J., Greenberg H. B., Kavey N. B. Hepatitis antigen. Detection of infectious blood donors. Lancet. 1969 Aug 2;2(7614):248–249. doi: 10.1016/s0140-6736(69)90011-7. [DOI] [PubMed] [Google Scholar]
  31. Gocke D. J., Kavey N. B. Hepatitis antigen. Correlation with disease and infectivity of blood-donors. Lancet. 1969 May 31;1(7605):1055–1059. doi: 10.1016/s0140-6736(69)91701-2. [DOI] [PubMed] [Google Scholar]
  32. HARRIS W. J., WESTWOOD J. C. PHOSPHOTUNGSTATE STAINING OF VACCINIA VIRUS. J Gen Microbiol. 1964 Mar;34:491–495. doi: 10.1099/00221287-34-3-491. [DOI] [PubMed] [Google Scholar]
  33. HAVENS W. P., Jr Viral hepatitis. Yale J Biol Med. 1961 Dec;34:314–328. [PMC free article] [PubMed] [Google Scholar]
  34. HOTCHIN J., COLLINS D. N. GLOMERULONEPHRITIS AND LATE ONSET DISEASE OF MICE FOLLOWING NEONATAL VIRUS INFECTION. Nature. 1964 Sep 26;203:1357–1359. doi: 10.1038/2031357a0. [DOI] [PubMed] [Google Scholar]
  35. HOTCHIN J. The biology of lymphocytic choriomeningitis infection: virus-induced immune disease. Cold Spring Harb Symp Quant Biol. 1962;27:479–499. doi: 10.1101/sqb.1962.027.001.046. [DOI] [PubMed] [Google Scholar]
  36. HUNTER W. M., GREENWOOD F. C. Preparation of iodine-131 labelled human growth hormone of high specific activity. Nature. 1962 May 5;194:495–496. doi: 10.1038/194495a0. [DOI] [PubMed] [Google Scholar]
  37. Hirschman R. J., Shulman N. R., Barker L. F., Smith K. O. Virus-like particles in sera of patients with infectious and serum hepatitis. JAMA. 1969 Jun 2;208(9):1667–1670. [PubMed] [Google Scholar]
  38. Hirschman R. J., Shulman N. R., Barker L. F., Smith K. O. Virus-like particles in sera of patients with infectious and serum hepatitis. JAMA. 1969 Jun 2;208(9):1667–1670. [PubMed] [Google Scholar]
  39. Holland P. V., Walsh J. H., Morrow A. G., Purcell R. H. Failure of Australia antibody to prevent post-transfusion hepatitis. Lancet. 1969 Sep 13;2(7620):553–555. doi: 10.1016/s0140-6736(69)90259-1. [DOI] [PubMed] [Google Scholar]
  40. Holmes A. W., Wolfe L., Rosenblate H., Deinhardt F. Hepatitis in marmosets: induction of disease with coded specimens from a human volunteer study. Science. 1969 Aug 22;165(3895):816–817. doi: 10.1126/science.165.3895.816. [DOI] [PubMed] [Google Scholar]
  41. Hotchin J. Kuru as a persisting tolerated infection. Lancet. 1966 Jul 2;2(7453):28–31. doi: 10.1016/s0140-6736(66)91752-1. [DOI] [PubMed] [Google Scholar]
  42. Krassnitzky O., Pesendorfer F., Wewalka F. Australia-SH-Antigen und Lebererkrankungen. Dtsch Med Wochenschr. 1970 Feb 6;95(6):249–253. doi: 10.1055/s-0028-1108445. [DOI] [PubMed] [Google Scholar]
  43. Krugman S., Giles J. P., Hammond J. Infectious hepatitis. Evidence for two distinctive clinical, epidemiological, and immunological types of infection. JAMA. 1967 May 1;200(5):365–373. doi: 10.1001/jama.200.5.365. [DOI] [PubMed] [Google Scholar]
  44. Krugman S., Giles J. P. Viral hepatitis. New light on an old disease. JAMA. 1970 May 11;212(6):1019–1029. doi: 10.1001/jama.212.6.1019. [DOI] [PubMed] [Google Scholar]
  45. LANG N. Ein Verfahren zum Nachweis von Reaktionen vom Typ der Antigen-Antikörperbindung. Klin Wochenschr. 1955 Jan 1;33(1-2):29–30. doi: 10.1007/BF01466920. [DOI] [PubMed] [Google Scholar]
  46. Lewkonia R. M., Finn R. ABO blood group distribution in serum hepatitis. Br Med J. 1969 Aug 2;3(5665):268–269. doi: 10.1136/bmj.3.5665.268. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Lichter E. A. Chimpanzee antibodies to Australia antigen. Nature. 1969 Nov 22;224(5221):810–811. doi: 10.1038/224810a0. [DOI] [PubMed] [Google Scholar]
  48. Maccallum F. O. Homologous Serum Hepatitis. Proc R Soc Med. 1946 Aug;39(10):655–657. [PMC free article] [PubMed] [Google Scholar]
  49. Mancini G., Carbonara A. O., Heremans J. F. Immunochemical quantitation of antigens by single radial immunodiffusion. Immunochemistry. 1965 Sep;2(3):235–254. doi: 10.1016/0019-2791(65)90004-2. [DOI] [PubMed] [Google Scholar]
  50. McCollum R. W. Serum antigens in viral hepatitis. J Infect Dis. 1969 Nov;120(5):641–643. doi: 10.1093/infdis/120.5.641. [DOI] [PubMed] [Google Scholar]
  51. Melartin L., Blumberg B. S. Production of antibody against "Australia antigen" in rabbits. Nature. 1966 Jun 25;210(5043):1340–1341. doi: 10.1038/2101340a0. [DOI] [PubMed] [Google Scholar]
  52. Millman I., Zavatone V., Gerstley B. J., Blumberg B. S. Australia antigen detected in the nuclei of liver cells of patients with viral hepatitis by the fluorescent antibody technic. Nature. 1969 Apr 12;222(5189):181–184. doi: 10.1038/222181b0. [DOI] [PubMed] [Google Scholar]
  53. Millman I., Ziegenfuss J. F., Jr, Raunio V., London W. T., Sutnick A. I., Blumberg B. S. The production of antibodies to Australia antigen in mouse ascites fluid. Proc Soc Exp Biol Med. 1970 Apr;133(4):1426–1431. doi: 10.3181/00379727-133-34705. [DOI] [PubMed] [Google Scholar]
  54. Mosley J. W., Barker L. F., Shulman N. R., Hatch M. H. Failure to detect an antigen associated with hepatitis in a community epidemic. Nature. 1970 Mar 7;225(5236):953–955. doi: 10.1038/225953a0. [DOI] [PubMed] [Google Scholar]
  55. Mosley J. W. Viral hepatitis: recent studies of etiology. Prog Liver Dis. 1970;3:252–268. [PubMed] [Google Scholar]
  56. Myllylä G., Vaheri A., Vesikari T., Penttinen K. Interaction between human blood platelets, viruses and antibodies. IV. Post-Rubella thrombocytopenic purpura and platelet aggregation by Rubella antigen-antibody interaction. Clin Exp Immunol. 1969 Mar;4(3):323–332. [PMC free article] [PubMed] [Google Scholar]
  57. Nowoslawski A., Brzosko W. J., Madaliński K., Krawczyński K. Cellular localisation of Australia antigen in the liver of patients with lymphoproliferative disorders. Lancet. 1970 Mar 7;1(7645):494–498. doi: 10.1016/s0140-6736(70)91580-1. [DOI] [PubMed] [Google Scholar]
  58. Okochi K., Murakami S. Observations on Australia antigen in Japanese. Vox Sang. 1968;15(5):374–385. doi: 10.1111/j.1423-0410.1968.tb04078.x. [DOI] [PubMed] [Google Scholar]
  59. Penttinen K., Käriäinen L., Myllylä G. Cytomegalovirus antibody assay by platelet aggregation. Arch Gesamte Virusforsch. 1970;29(2):189–194. doi: 10.1007/BF01249304. [DOI] [PubMed] [Google Scholar]
  60. Penttinen K., Myllylä G. Interaction in human blood platelets, viruses and antibodies. I. Platelet aggregation test with microequipment. Ann Med Exp Biol Fenn. 1968;46(2):188–192. [PubMed] [Google Scholar]
  61. Penttinen K., Myllylä G., Mäkelä O., Vaheri A. Soluble antigen-antibody complexes and platelet aggregation. Acta Pathol Microbiol Scand. 1969;77(2):309–317. doi: 10.1111/j.1699-0463.1969.tb04236.x. [DOI] [PubMed] [Google Scholar]
  62. Pesendorfer F., Krassnitzky O., Wewalka F. Immunelektrophoretischer Nachweis von "Hepatitis-Associated-Antigen" (Au-SH-Antigen. Klin Wochenschr. 1970 Jan 1;48(1):58–59. doi: 10.1007/BF01486135. [DOI] [PubMed] [Google Scholar]
  63. Popper H., Paronetto F., Schaffner F. Immune processes in the pathogenesis of liver disease. Ann N Y Acad Sci. 1965 Jun 30;124(2):781–799. doi: 10.1111/j.1749-6632.1965.tb19001.x. [DOI] [PubMed] [Google Scholar]
  64. Prince A. M. An antigen detected in the blood during the incubation period of serum hepatitis. Proc Natl Acad Sci U S A. 1968 Jul;60(3):814–821. doi: 10.1073/pnas.60.3.814. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Prince A. M. Immunologic distinction between I.H. and S.H. N Engl J Med. 1969 Jul 17;281(3):163–164. doi: 10.1056/NEJM196907172810311. [DOI] [PubMed] [Google Scholar]
  66. Purcell R. H., Gerin J. L., Holland P. V., Cline W. L., Chanock R. M. Preparation and characterization of complement-fixing hepatitis-associated antigen and antiserum. J Infect Dis. 1970 Feb;121(2):222–226. doi: 10.1093/infdis/121.2.222. [DOI] [PubMed] [Google Scholar]
  67. Purcell R. H., Holland P. V., Walsh J. H., Wong D. C., Morrow A. G., Chanock R. M. A complement-fixation test for measuring Australia antigen and antibody. J Infect Dis. 1969 Sep;120(3):383–386. doi: 10.1093/infdis/120.3.383. [DOI] [PubMed] [Google Scholar]
  68. SEVER J. L. Application of a microtechnique to viral serological investigations. J Immunol. 1962 Mar;88:320–329. [PubMed] [Google Scholar]
  69. STEINER J. W., CARRUTHERS J. S., BAUMAL R., KALIFAT S. R. Experimental immunologic liver injury and the concept of autodestruction. I. Can Med Assoc J. 1961 Dec 23;85:1369–1376. [PMC free article] [PubMed] [Google Scholar]
  70. Shoeman D. W., White J. G., Mannering G. J. Cytochrome P-420: tubular aggregated from hepatic microsomes. Science. 1969 Sep 26;165(3900):1371–1372. doi: 10.1126/science.165.3900.1371. [DOI] [PubMed] [Google Scholar]
  71. Shulman N. R., Barker L. F. Virus-like antigen, antibody, and antigen-antibody complexes in hepatitis measured by complement fixation. Science. 1969 Jul 18;165(3890):304–306. doi: 10.1126/science.165.3890.304. [DOI] [PubMed] [Google Scholar]
  72. Taylor P. E., Zuckerman A. J., Brighton W. D. Laboratory tests in viral hepatitis. J Clin Pathol. 1969 Nov;22(6):744–744. doi: 10.1136/jcp.22.6.744-a. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Turner G. C., White G. B. S.H. antigen in haemodialysis-associated hepatitis. Lancet. 1969 Jul 19;2(7612):121–124. [PubMed] [Google Scholar]
  74. Walsh J. H., Yalow R., Berson S. A. Detection of Australia antigen and antibody by means of radioimmunoassay techniques. J Infect Dis. 1970 May;121(5):550–554. doi: 10.1093/infdis/121.5.550. [DOI] [PubMed] [Google Scholar]
  75. Wright R., McCollum R. W., Klatskin G. Australia antigen in acute and chronic liver disease. Lancet. 1969 Jul 19;2(7612):117–121. doi: 10.1016/s0140-6736(69)92437-4. [DOI] [PubMed] [Google Scholar]
  76. ZUCKERMAN A. J., MCDONALD J. C. ABO BLOOD GROUPS AND ACUTE HEPATITIS. Br Med J. 1963 Aug 31;2(5356):537–538. doi: 10.1136/bmj.2.5356.537. [DOI] [PMC free article] [PubMed] [Google Scholar]
  77. Zuckerman A. J., Taylor P. E., Almeida J. D. Presence of particles other than the Australia-SH antigen in a case of chronic active hepatitis with cirrhosis. Br Med J. 1970 Jan 31;1(5691):262–264. doi: 10.1136/bmj.1.5691.262. [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. Zuckerman A. J., Taylor P. E. Persistence of the serum hepatitis (SH-Australia) antigen for many years. Nature. 1969 Jul 5;223(5201):81–82. doi: 10.1038/223081a0. [DOI] [PubMed] [Google Scholar]
  79. Zuckerman A. J. Viral hepatitis and the Australia-SH antigen. Nature. 1969 Aug 9;223(5206):569–572. doi: 10.1038/223569a0. [DOI] [PubMed] [Google Scholar]

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