Hepatitis-associated Antigen Research Articles

The Australia (Hepatitis-associated) Antigen

INTRODUCTION The accidental discovery of the Australia antigen (HAA) in 1963 by Blumberg and his coworkers is a classical example of biomedical serendipity. Its recognition not only stimulated a substantial amount of research into viral hepatitis, thereby adding considerably to our knowledge about this important disease, but has had far-reaching implications in the understanding of several other hepatic and systemic diseases. Indeed, its discovery may well be seen in the future to have been the all-important breakthrough in attempts at culture of the virus as a means of vaccine preparation for future prophylactic usage. THE DISCOVERY OF THE ANTIGEN Blumberg, a cytogeneticist working in the Philadelphia Institute for Cancer Research, was conducting a systematic study of the serum of patients who had received multiple blood transfusions. Using a technique of double diffusion in agar gel (Ouchterlony method) he searched for precipitating antibodies to inherited donor serum protein antigens, particularly those to low density betalipoproteins. A precipitating antibody was identified in the serum of a haemophiliac patient which reacted with an antigen which was quite dissimilar from lipoprotein antigens. This antigen was present in the serum of an Australian aborigine, and the term Australia antigen was coined (1, 2, 3,). This antigen is almost certainly identical to Prince’s SH antigen (4), and to avoid confusion the term hepatitis-associated antigen (HAA) is now considered by many to be more appropriate (5).

Malnutrition and hepatitis-associated antigen infection.

Malnutrition and Hepatitis-Associated Antigen Infection Get access Nutrition Reviews, Volume 31, Issue 10, October 1973, Pages 310–311, https://doi.org/10.1111/j.1753-4887.1973.tb07031.x Published: 01 October 1973

The unexpected outcomes of medical research: serendipity and the Australia antigenBlumberg BS, Alter HJ, Visnich S. A new antigen in leukemia sera [J Am Med Assoc 1965;191:541–546

The 'Australia Antigen' is found in the sera of some normal individuals from foreign populations. The total absence of the antigen from the sera of normal United States' subjects and its relatively high frequency in acute leukemia suggests that the presence of the antigen maybe of value in the diagnosis of early acute leukemia. Whether the antigen results from or precedes the leukemia process remains to be seen. (Abstract reproduced by permission of J Am Med Assoc 1965;191:541 - 546.) Many of the major discoveries in science have been the product of chance observations that were pursued by the curious mind to their plausible and provable explanation. Mendel's peas and, at least apocryphally, Newton's apple, come to mind as paradigm shifting observations that respectively opened the fields of genetics and established the laws of gravitation. Fleming's chance observation of the inhibition of bacterial growth in the presence of bread mold ultimately produced the first antibiotic. The unexpected link between the Australia antigen and the hepatitis B virus may be less encompassing than genetics or gravitation, but nonetheless is a classic example of a serendipitous observation pursued to major unexpected payoffs, including the prevention of post-transfusion hepatitis, the development of a vaccine, the prevention of hepatocellular carcinoma and laying the foundation for

Transmission of serum hepatitis. 1970

There is evidence that transmission of serum hepatitis is associated with transmission of virus-like particles, approximately, 20 millimicron in diameter, containing the Australia or serum hepatitis (SH) antigen, which is currently referred to as the hepatitis associated antigen (HAA). Virus-like particles containing HAA were in the following materials, inoculation of which produced serum hepatitis: (1) a pool of human plasma, (2) serum obtained during the acute phase of hepatitis from a recipient of the plasma pool, (3) a preparation of human thrombin, and (4) serum from a proved hepatitis carrier. The HAA appeared in the serum samples of 61 individuals inoculated with these materials; serum hepatitis developed in 38 of them. Inoculation of dilutions of the plasma pool showed that serum hepatitis can be transmitted by materials containing HAA in amounts too low to be detected by current techniques.

Transmission of Serum Hepatitis

There is evidence that transmission of serum hepatitis is associated with transmission of virus-like particles, approximately, 20 millimicron in diameter, containing the Australia or serum hepatitis (SH) antigen, which is currently referred to as the hepatitis associated antigen (HAA). Virus-like particles containing HAA were in the following materials, inoculation of which produced serum hepatitis: (1) a pool of human plasma, (2) serum obtained during the acute phase of hepatitis from a recipient of the plasma pool, (3) a preparation of human thrombin, and (4) serum from a proved hepatitis carrier. The HAA appeared in the serum samples of 61 individuals inoculated with these materials; serum hepatitis developed in 38 of them. Inoculation of dilutions of the plasma pool showed that serum hepatitis can be transmitted by materials containing HAA in amounts too low to be detected by current techniques.

Expression of Infectious Viral Particles by Primary Chimpanzee Hepatocytes Isolated during the Acute Phase of Non-A, Non-B Hepatitis

Liver wedge biopsies were obtained from chimpanzees during the acute phase of experimental non-A, non-B hepatitis infections. Primary chimpanzee hepatocytes were maintained for over 4 weeks in vitro with a serum-free medium supplemented with growth factors and hormones. The de novo synthesis and secretion of plasma proteins characteristic for differentiated primate hepatocytes were sustained under these culture conditions. Immunocytochemical staining for a non-A, non-B hepatitis-associated antigen revealed expression of this cytoplasmic marker during the culture period, indicating a persistence of the infection in vitro. Tissue culture medium derived from the hepatocyte cultures was used to inoculate a nonimmune chimpanzee. The animal subsequently displayed an increase in the serum levels of alanine aminotransferase, the development of histopathologic alterations indicative of viral hepatitis, and the appearance of liver cell cytoplasmic tubules diagnostic for non-A, non-B hepatitis. Concentrated tissue culture medium examined by electron microscopy contained virus-like particles with an average diameter of 39-46 nm, which exhibited an envelope and inner 37-nm core structure.

Hepatocellular Carcinoma in Saudi Arabia: Evaluation of Prognostic Factors

ABSTRACT The medical records and pathologic materials of 41 Saudi patients (22 males and 19 females) with confirmed diagnosis of hepatocellular carcinoma were reviewed retrospectively. None of the ...

Development of skin reaction to hepatitis B vaccines in man.

Microbiology and ImmunologyVolume 28, Issue 2 p. 257-259 ArticleFree Access Development of Skin Reaction to Hepatitis B Vaccines in Man Seiho Nagafuchi, Seiho Nagafuchi First Department of Internal Medicine, Kyushu University, Fukuoka, 812Search for more papers by this authorSeizaburo Kashiwagi, Seizaburo Kashiwagi First Department of Internal Medicine, Kyushu University, Fukuoka, 812Search for more papers by this authorTakatoshi Inoue, Takatoshi Inoue First Department of Internal Medicine, Kyushu University, Fukuoka, 812Search for more papers by this authorShuhei Imayama, Shuhei Imayama Department of Dermatology, Faculty of Medicine, Kyushu University, Fukuoka, 812Search for more papers by this author Seiho Nagafuchi, Seiho Nagafuchi First Department of Internal Medicine, Kyushu University, Fukuoka, 812Search for more papers by this authorSeizaburo Kashiwagi, Seizaburo Kashiwagi First Department of Internal Medicine, Kyushu University, Fukuoka, 812Search for more papers by this authorTakatoshi Inoue, Takatoshi Inoue First Department of Internal Medicine, Kyushu University, Fukuoka, 812Search for more papers by this authorShuhei Imayama, Shuhei Imayama Department of Dermatology, Faculty of Medicine, Kyushu University, Fukuoka, 812Search for more papers by this author First published: February 1984 https://doi.org/10.1111/j.1348-0421.1984.tb00678.xCitations: 7AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. REFERENCES 1Allison, A.C. 1974. Interactions of antibodies, complement components, and various cell types in immunity against viruses and pyogenic bacteria. Transplant. Rev. 19: 3– 55. 2Dudley, F.J., Giustino, V., and Sherlock, S. 1972. Cell-mediated immunity in patients positive for hepatitis-associated antigen. Br. Med. J. 30: 754– 756. 3Ito, K., Nakagawa, J., Okimoto, Y., and Nakano, H. 1972. Chronic hepatitis-migration inhibition of leukocytes in the presence of Australia antigen. N. Engl. J. Med. 286: 1005. 4Yeung Laiwah, A.A.C., Chaudhuri, A.K.R., and Anderson, J.R. 1973. Lymphocyte transformation and leukocyte migration-inhibition by Australia antigen. Clin. Exp. Immunol. 15: 27– 34. Citing Literature Volume28, Issue2February 1984Pages 257-259 ReferencesRelatedInformation

Immunological aspects of nephrotic syndrome in northern Nigeria.

Immunological aspects of 40 northern Nigerian children with nephrotic syndrome of recent onset are reported. Eight our of 30 had hepatitis-associated antigen in their sera. Hypocomplementaemia was rare. Measurement of serum C3, C4, and ASOT was not of diagnostic value. Proteinuria selectivity index was poor in half of the patients, and appeared t o depend on the severity of the kidney lesion. Abnormal immunofluorescence of kidney glomeruli to immunoglobulins, complement, Plasmodium malariae, and Plasmodium falciparum was found in 26 of the 29 children. The pattern of immunofluorescence was chiefly granular and was confined to the glomeruli. IgM was predominant. It was concluded that immunological reaction is involved in the pathogenesis of nephrotic syndrome in northern Nigerian children.

Inactivation of an agent of human non-A, non-B hepatitis by formalin.

Samples of serum (0.1 ml each) containing an agent of human non-A, non-B hepatitis of documented infectivity were incubated with formalin in a concentration of 1:1,000 at 37 C for 96 hr. Three colony-born infant chimpanzees were then inoculated with this formalin-treated serum; one received a single intravenous inoculation, and two received two subcutaneous inoculations one month apart. A fourth uninoculated chimpanzee served as a control. None developed recognizable non-A, non-B hepatitis during seven months of observation, as judged by normal aminotransferase levels in weekly serum samples, normal liver histology in liver biopsy specimens, and the absence of non-A, non-B hepatitis-associated antigen and antibody in their sera. All four chimpanzees were subsequently shown to be susceptible to non-A, non-B hepatitis when challenged with 0.1 ml of the untreated infectious serum 31 weeks after the initial inoculations.

Hepatic cancer in Chinese: a chapter in "georgraphic pathology".

Chinese patients display an unsually high incidience of hepatocellular carcinoma, as expressed in autopsy statistics, in hepatic biopsy specimens, in terms of ratios per 100,000 population, and with regard to standarized mortality rates. As in other ethnic groups, Chinese hepatoma patients show a pronounced numerical preponderance of male over female persons. Whether this sex difference is due to the existnece of cross-reactivity between HBsAg and a male-associated antigen remains to be confirmed. Of the Chinese patients residing abroad, those that were born in China (Idai) are at considerably higher risk of developing hepatic cancer than those born in their countries of residence (Erdai). This observation, per se, strongly argues in favor of an environmental, rather than racial, factor in the causation of such tumors. Among environmental factors suspected of contributing towards the observed inter-ethnic differences in hepatoma incidence rates, parasitic infestations appear to play no role in hepatocarcinogenesis, with the possible exception of clonorchiasis which has been implicated in cholangiocellular carcinomas. Dietary factors, hepatotoxins and alcoholism at beast are of only secondary etiological significance. Cirrhosis has been considered the most important etiological factor in the development of hepatocellular neoplasms. In Chinese patients the proportion of hepatomas arising in cirrhotic livers in many times higher than in Caucasian persons. Surveys have shown that the hepatitis-associated antigen has a high incidence of occurrence in persons of Chinese ancestry, especially those that were born in China, as well as in patients with hepatomas. It has been established that Chinese-Americans are at a very high risk for both hepatitis B virus infection and liver cell carcinoma. In addition, it has been hypothesized that in some families children will be infected with the virus by their mothers during the perinatal period, and that in some cases the infected person swill proceed through several stages (carrier state with retentions of antigen; development of chronic hepatitis; elaboration of cirrhosisis) to the development of hepatocellular carcinoma. It appears, then, that infection with the hepatitis B virus, during the earlier phases of life, is the single most important event in the eventual elaboration of hepatocellular carcinoma. The available epidemioligcal data on Chinese patients constitute a significant body of evidence in support of these conclusions.

Atypical Spider Nevi Distribution in Liver Disease

To the Editor.— A variety of cutaneous features are seen in liver disease of which the commonest, though not exclusive for liver disease, is the spider nevus. The face, neck, upper part of the thorax, and arms are the usual sites of occurrence. Our patient had florid spider nevi in thighs and knees, atypical sites of occurrence (Figure). Report of a Case.— A 44-year-old woman was admitted to the Gastroenterology Service for management of decompensated chronic alcoholic liver disease. Results of physical examination showed intense jaundice; she was fully conscious without asterixis. Florid spider nevi were noticed in the chest, back, shoulders, arms, and both thighs, as well as the knees. She had massive hepatomegaly, ascites, and bilateral leg edema. Laboratory studies disclosed the following values: WBC, 12,000/ cu mm; hematocrit, 34%; mean corpuscular volume, 100/cu μ; hepatitis-associated antigen, negative; bilirubin, 22.9 mg/dL; SGOT, 136 units; SGPT, 137 units; and

Efficacy and Safety of Cefamandole plus either Gentamicin or Tobramycin in Therapy of Severe Gram-Negative Bacterial Infections

Thirty-one patients with severe gram-negative bacterial infections were treated successfully with a combination of cefamandole nafate plus gentamicin or tobramycin. The patients were divided into two treatment groups: group 1 received low-dose therapy (80--100 mg of cefamandole nafate/kg per 24 hr plus 3 mg of either gentamicin or tobramycin/kg per 24 hr), and group 2 patients, who had suspected bacteremia, received high-dose therapy (170 mg of cefamandole nafate/kg per 24 hr plus 5 mg of either gentamicin or tobramycin/kg per 24 hr). All of the patients were clinically and bacteriologically cured of their primary infections. All four episodes of bacteremia were cleared within 24 hr after therapy was initiated. There was a uniform decrease in the rate of creatinine clearance which was slightly greater in group 2 patients; however, all creatinine clearance values were within the normal range and actually improved during therapy. There was no difference between the clearance values of the tobramycin-treated patients and gentamicin-treated patients. A few transient abnormalities in results of liver function tests occurred during the study. In one patient whose serum was positive for hepatitis-associated antigen, the alkaline phosphatase, aspartate aminotransferase, and bilirubin values were elevated on admisssion of the patient to the hospital, increased fivefold during therapy, and decreased to the base-line admission values six days after therapy; however, it is difficult to establish that this reaction was antibiotic-induced hepatic toxicity.

Health of the intensively treated hemophiliac, with special reference to abnormal liver chemistries and splenomegaly

Liver function abnormalities have been noted in intensively treated hemophiliacs, and have led to less aggressive application of pooled plasma products by some physicians. In a prospective study, liver function was abnormal in 68 of 98 hemophiliacs. The abnormalities of hepatic function tended to persist over a 1-yr study period. There was no correlation between these abnormalities and the age of the patient, the presence of hepatitis-associated antigen or antibody, the presence or absence of splenomegaly (which was found in 26 of 98 patients), the number of infusions of plasma products, the type of hemophilia, or the type of product infused. Titers of antibodies to cytomegalovirus were generally higher in hemophilic patients than in a control group of healthy volunteers. These abnormalities did not suggest that a less aggressive infusion regimen was indicated for the hemophiliac, but did suggest the need for careful long-term observation of such patients.

Health of the Intensively Treated Hemophiliac, With Special Reference to Abnormal Liver Chemistries and Splenomegaly

Liver function abnormalities have been noted in intensively treated hemophiliacs, and have led to less aggressive application of pooled plasma products by some physicians. In a prospective study, liver function was abnormal in 68 of 98 hemophiliacs. The abnormalities of hepatic function tended to persist over a 1-yr study period. There was no correlation between these abnormalities and the age of the patient, the presence of hepatitis-associated antigen or antibody, the presence or absence of splenomegaly (which was found in 26 of 98 patients), the number of infusions of plasma products, the type of hemophilia, or the type of product infused. Titers of antibodies to cytomegalovirus were generally higher in hemophilic patients than in a control group of healthy volunteers. These abnormalities did not suggest that a less aggressive infusion regimen was indicated for the hemophiliac, but did suggest the need for careful long-term observation of such patients.

Hepatitis-associated (Australia) antigen and Down's syndrome.

Hepatitis-Associated (Australia) Antigen (HAA) was detected in 13 (5.8%) of 223 patients with Down's syndrome and in 14 (3.7%) of 378 patients with other forms of mental retardation. The frequency of HAA was 2.4 per cent in 127 noninstitutionalized patients with Down's syndrome, and 10.4 per cent in 96 institutionalized patients. The frequency of HAA with Down's syndrome was lower on the average in Japan than in the United States or Germany. HAA was detected in one (1.3%) of 78 mothers of infants with Down's syndrome. Our study suggests that maternal exposure to HAA, as reflected by the presence of either HAA or anti-HAA, was not associated with the subsequent birth of an infant with Down's syndrome.

Fulminant Serum Hepatitis and Meningococcic Meningitis

A YOUNG soldier contracted concomitantly fulminant serum hepatitis and meningococcic meningitis. He recovered without sequelae. We could find no previous reports of these two diseases occurring concomitantly. We believe there may be a relationship between the two diseases. <h3>Report of a Case</h3> A 17-year-old basic trainee was admitted to the hospital Jan 13, 1973, complaining of fever and arthralgia. His temperature was 38.8 C (101.8 F) and he had a localized maculopapular rash over the ankles. The rash and the fever resolved over the next several days. On the fourth day, his bilirubin level rose to 5.9 mg/100 ml, alkaline phosphatase level to 340 milliunits per milliliter (mU/ml), lactic dehydrogenase level to 650 mU/ml, and serum glutamic oxaloacetic transaminase (SGOT) level to 1,450 mU/ml; the prothrombin time dropped to less than 10% of control, and the counterelectrophoresis test for hepatitis associated antigen (HAA) was positive. His temperature rose to 39.4

Incidence of hepatitis associated antigen HAA and homologous antibody in patients with rheumatoid arthritis.

The authors have studied the incidence of hepatitis associated antigen (HAA) and the homologous antibody in sera of patients with rheumatoid arthritis on the basis of (1) arthritis sometimes associated with viral hepatitis, (2) the possible infectious etiology of rheumatoid arthritis, and (3) observation on the possible pathogenetic role of HAA in some cases of polyarteritis nodosa. The presence of HAA and antibody titer gave constantly negative results in all subjects examined with the exception of one case which showed no signs of serological or histological hepatic involvement. On the basis of the results obtained, the negligible role of HAA in the etiopathogenesis of rheumatoid arthritis is underlined. However, the authors emphasize as suggestive the hypothesis that the characteristic histopathological alterations of rheumatoid arthritis may be mediated by an immunological reaction toward an infectious agent other than HAA, but operating through mechanisms similar to those of HAA in polyarteritis nodosa.

Incidence of hepatitis-associated antigen among male narcotic addicts in a drug treatment program.

Since September of 1972, the Drug Dependence Treatment Unit has been screening its narcotic addict patients for the hepatitis-associated antigen (HAA). Among a random population of 243 patients, 2% were positive HAA, a relatively high incidence.

Incidence of Hepatitis Associated Antigen HAA and Homologous Antibody in Patients with Rheumatoid Arthritis

Incidence of Hepatitis Associated Antigen HAA and Homologous Antibody in Patients with Rheumatoid Arthritis