Seroconversion from hepatitis B e antigen to anti-HBe in acute hepatitis B virus infection.
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Acute Disease↗
Biomedical subjects
M Mayumi
Publications and source records attributed to M Mayumi.
Studies on the outbreak of hepatitis A in an institute for mentally retarded children.
The authors encountered an outbreak of acute hepatitis in a public institute for mentally retarded children in Aomori Prefecture, Japan. Studies revealed that the probable vehicles of transmission of infection were contaminated water, contaminated meals, and close contact. From the clinical manifestations and epidemiological investigations of 41 affected children and staff members, an outbreak of hepatitis A was strongly suspected. Immune electron microscopy disclosed hepatitis A virus antigen particles in the stool specimens collected during the few days before and after peak transaminase elevation. Hepatitis A antigen was further extracted and purified. The antigen was the first reported recovery of the virus from a natural outbreak of hapatitis A in Asia. Subsequently, with the immune adherence hemagglutination test, using this extracted antigen, an increase in titer of antibody to hepatitis A antigen was demonstrated. Thus, this epidemic was serologically established as an outbreak of hepatitis A. Human immune serum globulin for the protection against hepatitis A was administrated to the 80 individuals concerned, and it was effective in preventing the clinical manifestation of hepatitis.
Adolescent↗
Duality of hepatitis B e antigen in serum of persons infected with hepatitis B virus: evidence for the nonidentity of e antigen with immunoglobulins.
Hepatitis B e antigen (HBeAg) is detected in the serum of some persons infected with hepatitis B virus. Owing to a close correlation of HBeAg and hepatitis B virus in the serum, it has been used as a practical indicator of infectivity. Two entities of HBeAg activity physicochemically different from each other were demonstrated in the serum of persons infected with hepatitis B virus. One was associated with a molecule that precipitated in 1.33 M ammonium sulfate solution, was larger than IgG, and had an electrophoretic mobility in the beta- to gamma-globulin regions and an isoelectric point of approximately pH 5.7. In contrast, the other HBeAg activity was associated with a molecule that was soluble in 1.33 M ammonium sulfate solution, was smaller than IgG, and had an electrophoretic mobility in the alpha-globulin region and an isoelectric point at pH 4.8. In spite of their marked physicochemical differences, a line of antigenic identity was clearly observed for them when they were tested against antibody to HBeAg by a them when they were tested against antibody to HBeAg by a double immunodiffusion method. The HBeAg activity associated with the large molecule was completely removed by an affinity column of anti-IgG, whereas the activity of the small molecule was not. These results indicate that, in the serum, HBeAg exists as a molecule smaller than IgG and also in association with IgG.
Electrophoresis, Disc↗
Infantile papular acrodermatitis (Gianotti's disease) and intrafamilial occurence of acute hepatitis B with jaundice: age dependency of clinical manifestations of hepatitis B virus infection.
Infantile papular acrodermatitis (IPA, Gianotti's disease) is a clinical manifestation of hepatitis B virus (HBV) infection in childhood. An epidemic of of IPA occurred in Matsuyama, Japan, where 153 patients in a pediatric clinic had IPA between October 1974 and March 1977. In this period 12 mothers and two fathers of patients contracted acute hepatitis B with overt jaundice three to 14 months after their offspring had IPA. Analysis of the subtype of hepatitis B surface antigen (HBsAg) in the infants and their jaundiced mothers and/or fathers disclosed that HBV was transmitted from the infants. All of the index cases were one year old or younger, although the age of patients with IPA ranged from three months to 10 years. In approximately 40% of patients with IPA who were one year old or younger, HBs antigenemia persisted for one year. These facts suggested that the contraction of IPA in children, especially those one year old or younger, was an important route toward establishment of the carrier state of HBV which maintains the reservoir of this virus in the community.
Acrodermatitis↗
Incomplete inactivation of hepatitis B virus after heat treatment at 60 C for 10 hours.
A 10(-3) dilution of pooled serum (positive for hepatitis B e antigen and DNA polymerase activity) containing hepatitis B virus (HBV) in a titer 10(5) times the chimpanzee-infectious dose, was heated under water maintained at 60 C for 10 hr. There was a twofold decrease in the titer of hepatitis B surface antigen (HBsAg) as measured by reverse passive hemagglutination after the heat treatment. The heated, diluted serum was still infectious and caused HBV infections in both seronegative chimpanzees given 1-ml iv inoculations of the diluted serum. However, the infectivity of the virus was decreased approximately 10(4)-fold by heat treatment as judged from the prolonged incubation period before appearance of HBsAg in blood. This figure was based on the inverse linear relation between the dose of HBV and the incubation period. The incomplete inactivation of HBV by heat treatment at 60 C for 10 hr should be emphasized because it is widely accepted that heat treatment destroys HBV.
Animals↗
Failure of antibody to e antigen to precipitate Dane particles containing DNA polymerase activity and hepatitis B core antigen.
Serum samples of 67 asymptomatic carriers were tested for Dane particles by electron microscopy, and for e antigen by immunodiffusion, as well as for hepatitis B antigen-associated DNA polymerase activity, and four samples enriched with respect to Dane particles were selected. Hepatitis B antigen particles in them were separated from e antigen and concentrated by centrifugation, and the Dane-rich preparations were incubated with buffer, antibody to e antigen (anti-HBe) or antibody to hepatitis B surface antigen. After centrifugation, the supernatant was tested for DNA polymerase activity, and both supernatant and precipitate were tested for hepatitis B core antigen (HBcAg) by the immune adherence haemagglutination method after the coat of the Dane particles had been disrupted with NP-40 and 2-mercaptoethanol. It was found that anti-HBe did not precipitate Dane particles as measured by DNA polymerase activity and HBcAg. On the basis of the results obtained, it has been concluded that e antigen does not exist on the surface of hepatitis B virions.
Antibodies, Viral↗
Discovery of a lectin with affinity for the HBs antigen.
An extract of marguerite leaves was found to contain an agglutinin which has affinity for HBs (adr type) antigen-sensitized sheep erythrocytes and for pure HBs antigen. This agglutinin activity was inhibited by the plasma of hepatitis patients who were known to have circulating HBs antigen. The agglutinin activity was also inhibited by 0.03M N-acetylneuraminic acid.
Animals↗
Clinical significance of e-antigen/anti-e, with special reference to HBc-antigen in the liver.
e-antigen and anti-e were assayed in sera of asymptomatic HBs-Ag carriers and of patients with liver diseases. Thirteen out of 34 (38.2%) asymptomatic carriers were positive for e-antigen, which was in sharp contrast to the reports from USA and Europe. e-antigen was detected to a greater extent in patients with chronic active hepatitis, reversely anti-e in patients with chronic persistent hepatitis. However, e-antigen was found rarely in patients with cirrhosis and never in 23 cases with hepatoma positive for HBs-Ag. HBc-Ag in the liver was detected in 4 out of 8 e-antigen positive asymptomatic carriers and in 4 out of 5 patients with chronic liver diseases with e-antigen respectively, and moreover in 3 out of 14 anti-e positive cases, so that the presence of anti-e did not necessarily mean the negativity of HBc-Ag in the liver. Anti-HBc titer, however, was lower in anti-e positive sera than in e-antigen positive ones. This may implicate the decreased replication of HBV in cases with anti-e. These results emphasize that the investigation of e-antigen/anti-e is mandatory for the evaluation of the prognosis of asymptomatic carriers and of patients with chronic hepatitis.
Adult↗
Hepatitis B e antigen and infectivity of hepatitis B virus.
For confirmation of the difference in the infectivity of hepatitis B surface antigen (HBS Ag)-positive serum according to differences in the e antigen system, four chimpanzees were inoculated with serum positive for hepatitis B e antigen (HBe Ag), and three chimpanzees were inoculated with serum positive for antibody to HBe Ag (anti-HBe). Since the infectivity titrations are not yet completed, the end infectivity titer of each serum is not known. All four chimpanzees given injections of 10(-1), 10(-4), or 10(-8) dilutions of HBe Ag-positive serum developed hepatitis B virus infection, whereas the one chimpanzee injected with undiluted anti-HBe-positive serum became infected, and other chimpanzees injected with diluted anti-HBe-positive sera did not. As judged from the length of the incubation period before appearance of HBS Ag in blood, there seemed to be a remarkable difference in infectivity between the HBe Ag-positive serum and the anti-HBe-positive serum; the former serum was 10(8) times more infectious than the latter.
Animals↗
High prevalence of e antigen among healthy blood donors carrying hepatitis B surface antigen in Japan.
Hepatitis B surface antigen (HBsAg) was detected by an immune adherence haemagglutination method in the serum samples of 292 voluntary, apparently healthy blood donors at four regional blood centres in Japan. Their serum samples were concentrated 3-fold and tested for e antigen (e Ag) and antibody to e (anti-e) by immunodiffusion. The e Ag was found in 41 samples (14.0%) and anti-e in 57 (18.6%). When 100 randomly selected serum samples containing HBsAg were tested as they were (unconcentrated), and at 3- and 5-fold concentrations, e Ag was detected in 3, 16 and 27, respectively, and anti-e in 10, 21 and 26. Subtypes of HBsAg were similar in carriers with e Ag and with anti-e. There is a high prevalence of e Ag in healthy individuals in Japan. There are also high rates of vertical transmission of hepatitis B virus from mothers to children, as well as a high incidence in the past of post-transfusion hepatitis. This is further evidence that e antigen is a marker for the infectivity of hepatitis B virus in carriers.
Blood Donors↗
A direct immunofluorescence method for the detection of hepatitis B core antigen in formalin-fixed and gelatin-embedded liver specimens.
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Fluorescent Antibody Technique↗
Anti-HBc titer in relation to the etiological role of hepatitis B virus in primary hepatocellular carcinoma.
The antibody to hepatitis B core antigen (anti-HBc) is belived to be a marker for natural infection with hepatitis B virus (HBV). In order to study the etiological role of HBV in relation to primary hepatocellular carcinoma (PHC), the anti-HBc in sera of 31 PHC patients was surveyed by the immune adherence hemagglutination method which was about 10 times more sensitive than the complement fixation method. Twenty two out of 31 PHC cases were positive for anti-HBc (71.0%). The is a higher rate of incidence than that of HBs-Ag (51.6%). However, high anti-HBc titer above 2(10) which might reflect current infection with HBV was observed in 15 of these 22 cases. The remaining 7 cases had a titer lower than 2(8); 5 of these patients had neither HBs-Ag nor anti-HBs in their sera. As control, 37 anti-HBs positive blood donors with no definite liver disease were surveyed for anti-HBc titer. Thirty-four of them were positive, but in the majority of cases, the serum titer was less than 2(9), which might only reflect previous infection with HBV. These findings indicate that not only the prevalence of anti-HBc, but also the determination of its real titer is quite important for studying the relationship of HBV to PHC.
Carcinoma, Hepatocellular↗
Correlation between titer of antibody to hepatitis B core antigen and presence of viral antigens in the liver.
Liver specimens of 31 autopsied cases of liver cirrhosis who had had detectable levels of antibody to hepatitis B core antigen (anti-HBc) inthe serum were stained for hepatitis B core antigen (HBcAg) and hepatitis B surface antigen (HBSAg) by the direct immunofluorescence method. Their premortem serum samples were tested for HBSAg, antibody to HBSAg (anti-HBS) and anti-HBC. Persistent hepatitis B virus (HBV) infection as judged by circulating and/or liver HB antigens was identified in 18 patients, and all of them revealed a high titer of anti-HBC ranging from 2(11) to 2(16) by the immune adherence hemagglutination method. In contrast, anti-HBC titer of the remaining 13 patients without detectable HB antigens was less than 2(9), and the geometric mean titer of anti-HBC of the patients with persistent HBV infection was significantly higher than that of the patients without (13.9+/-1.55 versus 7.23+/-1.30; t test, P less than 0.001). A combination of circulating anti-HBS and hepatic HB antigens was found in one patient, whose serum revealed an anti-HBC titer of 2(12). On the basis of these results, a high titer of anti-HBC in the serum (immune adherence hemagglutination titer of 2(11) or more) seems to be a reliable indicator of persistent HBV infection in the liver.
Antibodies↗
Determination of e antigen and antibody to e by means of passive hemagglutination method.
A simple and sensitive method was developed for the detection of e antigen and antibody to e (anti-e) by means of the passive hemagglutination (PHA) method. Sheep erythrocytes were fixed by glutraraldehyde and coated with either e antigen or anti-e which had been specifically purified from plasma of asymptomatic carriers of hepatitis B antigen by affinity column chromatography, and then by gel filtration on Sephadex G-200. A gain in specific activity of more than 2000-fold for e antigen and 100-fold for anti-e was achieved as compared with the original plasma pool which was used as the source for purification. The PHA method was at least 300 times more sensitive than the conventional immunodiffusion method both for e antigen and anti-e assays. When the PHA method was applied for neat serum samples of 80 asymptomatic carriers, e antigen was found in 21.3% and anti-e in 62.5%, at rates much higher than those determined by immunodiffusion for the identical serum samples at 3-fold concentration (16.3 and 30.0%, respectively).
Antibodies, Viral↗
Letter: Decreasing frequency of e antigen with age in serum of symptom-free carriers of hepatitis B antigen.
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Adolescent↗
An epidemic of infantile papular acrodermatitis (Gianotti's disease) in Japan associated with hepatitis-B surface antigen subtype ayw.
An epidemic of infantile papular acrodermatitis (I.P.A.) (Gianotti's disease) occurred in Matsuyama City, in south-east Japan in 1974-75. Patients ages ranged from less than one year to eight years. Hepatitis-B surface antigen (HBsAg) was detected by an immune adherence haemagglutination method in the serum samples of 48 of the 54 patients tested. HBsAg subtypes were determined by a haemagglutination-inhibition method. ayw antigens were identified in 42 patients and adr antigens in 3; it was not possible to determine subtypes in the remaining 3 patients because antigen titres were too low. Since subtype ayw and I.P.A. are extremely rare in Japan, the association of the disease with HBsAg subtype ayw is regarded as being most significant.
Acrodermatitis↗
Hepatitis B antigen-associated deoxyribonucleic acid polymerase activity and e antigen/anti-e system.
Serum samples of 403 asymptomatic blood donors carrying hepatitis B surface antigen (HB5Ag) were concentrated threefold and tested for e antigen and antibody to e antigen (anti-e) by immunodiffusion. Hepatitis B antigen (HBAg)-associated deoxyribonucleic acid (DNA) polymerase activity was specifically determined by the difference in incorporation of [methyl-3H]thymidine 5' -triphosphate into DNA by an aliquot of centrifuged serum samples after it had been treated either with normal rabbit serum or with rabbit antibody to HBSAg. All of 58 serum samples containing e antigen revealed HBAg-associated DNA polymerase activity, whereas none of 96 samples containing anti-e did. In the remaining 249 samples in which neither e antigen nor anti-e was found, 62 showed specific DNA polymerase activity, although at lower levels than the samples containing e antigen.
Antibodies, Viral↗