IMPACT OF AUSTRALIA ANTIGEN (HB,Ag) ON HEPATITIS ALTON I. SUTNICK, M.D.
When Australia antigen was discovered in 1963,1 it was not expected that it would herald a new era in hepatitis research. The first publication on the association of viral hepatitis with the presence of this antigen in the blood appeared in 1967,^ and this opened the door to a long series of confirmatory studies in many different laboratories all over the world. In 1969 the Hospital of the University of Tokyo became the first to screen blood donors for the presence of Australia antigen as a means of decreasing the incidence of post-transfusion hepatitis. Within 2 years this became virtually a universal procedure. Although the major emphasis was on the role of Australia antigen in posttransfusion hepatitis, attention was also paid to the original observation that this antigen was detectable in hepatitis patients who had no history of blood transfusion or other parenteral exposure. It was thus proposed that Australia antigen could be transmitted by nonparenteral means.^ This view was strengthened by the studies of Krugman and Giles,^ in which preparations containing Australia This work was supported by U.S.P.H.S. Crants CA-06551 and RR-05539 from National Institutes of Health, and by an appropriation from the Commonwealth of Pennsylvania. Address for reprints: Alton 1. Sutnick, M.O., Associate Director, The Institute for Cancer Research, The Eox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111.
Erom The Institute for Cancer Research, The Fox Chase Cancer Center, Philadelphia, Pennsylvania
antigen were orally administered to mentally retarded youngsters on adtnission to a state institution. They were subsequently noted to develop mild hepatitis associated with Australia antigen in their blood. Hepatitis A and Hepatitis B These observations raised serious questions about the time-honored designation of 2 viruses causing hepatitis, the infectious hepatitis (IH) virus and serum hepatitis (SH) virus. It now appears that an agent which can be identified in the blood can be transmitted either parenterally or nonparenterally. These concerns have led hepatologists to return to a nomenclature of hepatitis A (not associated with Australia antigen) and hepatitis B (associated with Australia antigen). Hepatitis B may be definitively identified by the presence of Australia antigen. Hepatitis A at present is identified only by the absence of Australia antigen, although serologic tests for hepatitis A are under development.-'' Hepatitis A is acknowledged as being more contagious, but we no longer recommend the use of the terms serum hepatitis and infectious hepatitis in an etiologic sense.
INTERNATIONAL JOURNAL OE DERMATOLOGY
These, in fact, are epidemiologic terms. Serum hepatitis indicates a route of infection or a means of infection. This is analogous to the use of the term nosocomial infection to indicate how that infection was contracted. But what is this Australia antigen that identifies hepatitis B? In 1968 it was viewed under the microscope as a spherical particle about 20 nm in diameter which resembled a virus.'' However, the inability to detect nucleic acids in this particle raised serious doubts as to its capability of replication. Larger particles 42 nm in diameter, first discovered by Dane et al.,' are probably the true infectious agents of the disease. These larger particles are coated with Australia antigen. Accordingly, the currently recommended nomenclature is based on the structure of the 42 nm particle. Australia antigen has been renamed hepatitis B surface antigen (HBsAg) and the internal component is called hepatitis B core antigen (HB,Ag). Clinical Uses of HB Ag Testing for HB«Ag is now used widely in hospitals, blood banks, clinical laboratories and research laboratories. The most common use of the test is for screening of blood donors. This is now one of the certification requirements of the American Association of Blood Banks. An investigation of the effectiveness of testing blood donors for MBsAg and excluding those found to be positive was carried out at the Philadelphia General Hospital.'* Before the institution of this screening program, post-transfusion (mostly anicteric) hepatitis occurred in 17.9% of transfused patients. This has now decreased to 5.9%. These results emphasize the importance of establishing such testing programs. Another widely used clinical application of the HBsAg test is in the diagnosis
of atypical acute or chronic hepatitis. A positive test would favor the diagnosis but a negative test would not exclude it. The test is also of value in determining the prognosis of a patient with acute hepatitis in relation to the development of chronic hepatitis. In patients with acute hepatitis, the presence of HB^Ag is transient and disappears during the course of the disease. It rarely persists for longer than 2 to 3 weeks, and in many instances, may be present for only a few days. Persistence of the antigen for 6 weeks or more is highly suggestive that the patient may develop a chronic form of hepatitis, even if his clinical course has improved. Testing for HB^Ag has been used as a means of surveillance in institutions for the mentally retarded. Persistence of HB^Ag is common among patients with Down's syndrome in large crowded institutions.'^ These patients may be a reservoir for the spread of hepatitis, which is a serious problem in many of these institutions. Perhaps one might consider decentralization of these institutions into small units, where the rapid spread of the infectious agent might be contained. Surveillance of other high-risk groups is another valuable use of the test.^" These include clinical and research laboratory personnel; personnel of blood banks and blood donor stations, pathology laboratories, and morgues; and personnel working in hemodialysis units. Another potential use of the test is for screening some individuals who might be potential sources of infection for others; these include food handlers, patients entering hemodialysis programs, dentists and dental assistants. Current evidence suggests that the HB^Ag positive health care workers do not constitute an undue We now are reasonably certain of its role in viral hepatitis and its value in
IMPACT OF AUSTRALIA ANTICEN • Sutnick
prevention and diagnosis of the disease. But Australia antigen still has its mysteries. It is associated with some diseases other than hepatitis (leukemia, Hodgkin's disease, Down's syndrome, cbronic renal disease, lepromatous leprosy, primary hepatocellular carcinoma) and these relationships still remain to be fully explained. Many of these conditions appear to be associated with impairment of the cellular immune response. The presence of persistent Australia antigen in the blood of many people throughout the world without evidence of clinical hepatitis raises serious concerns about the carrier state, immunologic and genetic responses, and individual differences in susceptibility to disease. The studies on Australia antigen have answered many questions and raised others. It still provides a rich field for research in human disease. References 1. Blumberg, B. S., Polymorphisms of the serum proteins and the development of isopreclpitins in transfused patients. Bull. N. Y. Acad. Med. 40:377, 1964. 2. Blumberg, B. 5., Gerstley, B. |. S., Hungerford, D. A., London, W. T., and Sutnick, A. I., A serum antigen (Australia antigen) in Down's syndrome, leukemia and hepatitis. Ann. Intern. Med. 66:924, 1967. 3. Sutnick, A. I., London, W. T , Millman, L, Coyne, V. E., and Blumberg, B. S., Viral
hepatitis: revised concepts as a result of the study of Australia antigen. Med. Clin. N. Am. 54:805, 1970. Krugman, S., and Ciles, |. P., Vital hepatitis: new light on an old disease. |AMA 212:1019, 1970. Feinstone, S. M., Kapikian, A. Z., and Purcell, R. H., Hepatitis A: detection by immunoelectron microscopy of a virus-like antigen associated with acute illness. Science 182: 1026, 1973. Bayer, M. E., Blumberg, B. S., and Werner, B., Particles associated with Australia antigen in the sera of patients with leukemia, Down's syndrome and hepatitis. Nature 218:1057, 1968. Dane, D. S., Cameron, C. H., and Briggs, M., Virus-like particles in serum of patients with Australia antigen-associated hepatitis. Lancet 1:695, 1970. Senior, J. R., Sutnick, A. I., Coeser, E., London, W. T., Dahike, M. B., and Blumberg, B. S., Reduction of post-transfusion hepatitis by exclusion of Australia antigen from donor blood in an urban public hospital. Am. J. Med. Sci. 267:171, 1974.
9. Sutnick, A. I., London, W. T., Cerstley, B. J. S., Cronlund, M. M., and Blumberg, B. S., Anicteric hepatitis associated with Australia antigen: occurrence in patients with Down's syndrome. JAMA 205:670, 1968. 10. Sutnick, A. I., London, W. T., Millman, I., Gerstley, B. J. S., and Blumberg, B. S., Ergasteric hepatitis: endemic hepatitis associated with Australia antigen in a research laboratory. Ann. Intern. Med. 75:35, 1971. 11. Alter, H. |., Chalmers, T. C , Ereeman, B. M., Lunceford, J. L., Lewis, T. L., Holland, P. V., Pizzo, P. A., Plotz, P. H., and Meyer, W. ]., Ill, Do health care workers with HB,Ag put their contacts at risk? N. Engl. J. Med. 292: 454, 1975.
BALDNESS was widespread if we judge from mummies. It was treated as it is today, with castor oil. But Egyptians added to it the fat of the hippopotamus, of the crocodile, cat, snake, an ibex, the foot of a donkey, the leg of a hound, or the quills of a hedgehog.—Chaliounqui, P.: Magic and Medical Science in Ancient Fgypt. London, Hodder and Stoughton, 1963, p. 136.