Search

There is little recent data of the seroprevalence of hepatitis B in Australia. We have surveyed a large cohort of endoscopy patients attending a teaching hospital in central Sydney, and related the presence of hepatitis B virus (HBV) markers with putative risk factors for exposure using the SAS statistical package. Of the 2115 patients tested: 2.1% (45/2115) were HBV surface antigen positive, 0.75% (14/2115) viraemic, 9.5% (200/2115) anti-HBs and anti-HBc positive, 20.1% (430/2115) vaccinated (anti-HBs only) and the remaining 70% were susceptible. The adjusted OR of HBV infection was significantly increased in patients who had been diagnosed with human immunodeficiency virus (36.3-fold), born in Asia or Pacific islands (12.4-fold), born in North Africa, Middle East & Mediterranean countries (6-fold) or born abroad elsewhere in the world (2.7-fold), had household contact with someone diagnosed with hepatitis between 1980 and 1990 (3.9-fold), injected drugs between 1980 and 1990 (4.4-fold), resided in a military establishment for 3 months (2.3-fold) or in a hospital for 3 months (2.2-fold), never been vaccinated for hepatitis B (2.8-fold), received blood transfusion due to an accident and/or a haemorrhage (1.92-fold) and finally been a male gender (1.59-fold). The prevalence of HBV in this hospital population was higher than predicted on the basis of notifications to the passive surveillance scheme. Most HBV patients had multiple risk factors for infection, but the hierarchy of odds ratios provides a rational basis for targeted programmes to identify asymptomatic HBV carriers who might benefit from treatment.

Natural variation in hepatitis B virus (HBV) was studied in asymptomatic carriers originating from countries of high endemicity. HBV DNA was detected by dot blot and/or polymerase chain reaction (PCR) in 34 of the 184 members of 22 new immigrant families who agreed to be tested after one of their children had been found to have current or past hepatitis B in a school survey. PCR products from both the S and distal-X pre-C regions were sequenced. One vaccinated child had the classical "escape" mutation at amino acid position 126 in the S-gene and two other children and two adults had other substitutions at amino acid positions 133, 120, 165, and 159. Mutations were more frequent in the distal-X pre-C region and included two pre-C mutants and 13 other amino acid substitutions. The strains originating in the various countries were placed in almost identical groups by phylogenetic analysis using each amplicon, and determination of subtype by antigenic analysis gave the same result as sequencing. The S-data allowed recognition of three dominant strains within genotype B, while the distal-X pre-C data provided better discrimination between family groups. No change was found when the sequence of samples obtained for the study was compared with those collected from 14 of the children two years earlier. There was some evidence of horizontal spread in addition to vertical transmission. Reports of mutations of HBV in patients with severe or unusual clinical features should be interpreted with caution until the prevalence of the mutant in asymptomatic carriers has been determined.

Thirty-five 1-day-old Pekin-Aylesbury ducks were inoculated intravenously or intraperitoneally with duck hepatitis B virus, and the time-course of infection was examined by Southern-blot, dot-blot, and in situ hybridization and by immunohistochemistry. Randomly scattered single infected hepatocytes were first seen on days 1 and 2 after inoculation and by day 3 occurred as single cells, pairs, and groups of 5-10 adjoining cells. From day 4 after inoculation all hepatocytes were positive for duck hepatitis B surface antigen and deoxyribonucleic acid. Duck hepatitis B virus deoxyribonucleic acid levels in liver extracts and serum increased logarithmically from days 2 to 3 to a plateau by days 4 to 5 after inoculation. Infected and control birds showed no significant differences during the first 7 days in terms of liver histology, hepatocyte morphology, or mitotic activity. It was concluded that (a) virus gains access to randomly distributed hepatocytes without first replicating in other cell types, and then begins disseminating to adjacent cells following anatomic boundaries; (b) markers of infection in liver and serum show reproducible kinetics, thus making this in vivo system amenable to further quantitative study; and (c) hepatocytes in this system are highly permissive to virus replication without the development of significant cytopathology.

Natural Duck Hepatitis B Virus (DHBV) infection has been studied in Australian ducks. Sera from 430 Pekin Aylesbury cross-bred ducks taken from three separate flocks were examined for duck hepatitis B virus (DHBV) DNA using a DNA dot hybridisation assay. In one flock there was significant infection with DHBV (98/140), but none was detectable in the other two flocks. Episomal DHBV DNA in liver tissue was demonstrated by gel blot hybridisation only in birds with DHBV DNA in serum. Polymerase-labelled DHBV DNA migrated as expected for linear double-stranded DNA 3.1 kilobase (kb) in length. Virus particles with characteristic DHBV morphology were observed in DHBV DNA-positive serum on electron microscopy. No overt morbidity has been noted in naturally infected ducks, but moderately severe hepatitis was found in 3/40 ducks examined histologically. These 3 ducks had DHBV DNA in serum and liver tissue. Mild hepatitis was observed in 27 ducks, but, in these, there was no correlation between the hepatitis and the presence of DHBV in serum or in liver tissue. This is the first report of DHBV in Australia. An animal model may now be established to study aspects of Hepadna virus infection which are pertinent to Hepatitis B virus (HBV) disease in man.

Three serum samples derived from healthy hepatitis B surface antigen-negative subjects were found to be reactive for hepatitis B virus (HBV) DNA sequences when assayed by DNA dot-hybridization. All three results were shown to be due to the presence of sequences which reacted with residual bacterial plasmid vector sequences in the DNA probe, and no evidence of HBV markers was demonstrated in the sera. This is the first report of a false-positive result with the HBV DNA dot-hybridization assay.

Tissues from a 10-week-old Pekin duck, experimentally infected at 1 day of age with duck hepatitis B virus (DHBV), were examined for the presence of replicative levels of DHBV DNA by in situ and Southern blot hybridization. Hepatocytes, pancreatic lymphoid follicle, exocrine, and endocrine cells, and splenic mononuclear cells all contained DHBV DNA localized predominantly to the cytoplasm of infected cells. Duck hepatitis B surface antigen distribution in the same tissues correlated well with the presence of DHBV DNA in many of these cells. In hepatocytes and pancreatic islet cells, 60% of DHBV DNA was present as single-stranded DNA, indicating the likelihood of ongoing virus replication in these cell types and providing further evidence that hepadnavirus DNA replication occurs largely within the cell cytoplasm. In contrast, DHBV in mononuclear cells within splenic germinal centers was wholly double-stranded, suggesting that limited, if any, DHBV DNA replication was occurring in this cell type. These data provide further information about the pathogenesis and cell-specific sites of DHBV infection.

The hepatitis B virus (HBV) DNA dot-hybridization assay has been introduced into clinical practice in Australia and its behaviour compared with that of the classic markers of HBV infection. A good correlation exists between the presence of HBV DNA and that of hepatitis B e antigen but the degree of dissociation between HBV DNA and the e:anti-e system was smaller than earlier studies would suggest. Patients who are seronegative for hepatitis B surface antigen (HBsAg), whether they possess anti-HBs, anti-HBc HBc (antibody to the core antigen), or neither antibody, gave uniformly negative results for the presence of HBV DNA. Theses results are different from those that were obtained from earlier studies of patients with chronic liver disease.

Sera from 87 patients with acute sporadic viral hepatitis were tested for the presence of the Australia-SH antigen. Forty-three were positive by the complement-fixation test, but only 24 of these reacted in the gel-diffusion test. The antigen was equally distributed in infectious and serum hepatitis. The relationship of naturally occurring antigen-positive hepatitis to the Willow-brook MS-2 type is discussed.

Duck hepatitis is a convenient model of hepatitis B virus (HBV) infection, but the lack of immunological reagents hampers investigation of pathogenesis and vaccine development. The aim of this study was to define T-cell epitopes in the surface peptide recognized by vaccinated immune birds. Blastogenesis assays were used to test the proliferative response of spleen mononuclear cells to synthetic peptides spanning the pre-S/S region in 22 naïve and 13 immunized and challenged immune ducks. Roughly ≥50% of the immune ducks responded to five immunodominant peptides eliciting a statistically greater proliferative response than in naïve birds. Fewer ducks responded to an additional six peptides. No statistically significant difference could be shown for the response to 11 peptides between the immune ducks and the naïve ducks. There was no clustering of the immunodominant peptides which were located throughout the surface antigen at sites of major swings in hydrophobicity. A number of peptides which induce lymphoblastogenesis in vaccinated immune ducks have been identified. Their role in spontaneous recovery from duck hepatitis B infection merits investigation. [ABSTRACT FROM AUTHOR]