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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.

Using molecular finger-printing, we provided evidence that, in a children's day-care centre, a known hepatitis B virus (HBV) hepatitis B e antigen (HBeAg) carrier transmitted HBV to another child (the index case). The chronic HBV carrier had an exudative skin lesion and a history of biting. We sought to identify other at-risk children and prevent further transmission. Blood samples were collected and tested serologically for HBV. Of the 90 other children, 78 (87 per cent) were tested and none had serological evidence of HBV infection; 73 (81 per cent) were of Caucasian background; 38 (49 per cent) had a history of HBV immunisation with serological confirmation. Therefore, 1 (2.4 per cent, 95 per cent confidence interval 1.0 to 12.8 per cent) of the 41 known susceptible contacts became infected. The risk of horizontal HBV transmission in a children's day-care centre is low but not negligible. Staff and children should be vaccinated when a child in a day-care centre is a known HBV carrier.

Nosocomial transmission of hepatitis B virus (HBV), associated with interventional procedures, has been attributed to its survival on improperly decontaminated instruments. To date, guidelines for chemical disinfection of potentially contaminated heat-sensitive instruments have been based largely on extrapolation of data from in-vitro disinfectant testing. Direct infectivity testing has not been possible for HBV because of the lack of a practical culture assay or susceptible experimental animal model. In this study the related duck hepadnavirus was used to simulate in-vivo transmission of a HBV during surgery, and to evaluate the effectiveness of 2% glutaraldehyde disinfection of surgical laparoscopes. Multiple laparoscopic liver biopsies were performed on 'biohazardous' duck hepatitis B (DHBV) positive ducks. Laparoscopes were then subjected to different disinfection regimes using 2% glutaraldehyde, and residual infectivity tested by placing their tips into the peritoneal cavities of uninfected four-day-old ducklings. Direct transmission of DHBV occurred in all ducks when laparoscopes were not washed. Rinsing with water lowered the transmission rate to 64% and no infection transmission occurred after 5 min of contact time with the disinfectant. In contrast, previous in-vitro studies had shown complete viral inactivation after a shorter period of disinfection. It is postulated that the longer inactivation time observed in our study may be a result of surface interactions of virus and instrument, interfering with disinfectant access or activity. Tests of instrument surface samples for viral DNA by the polymerase chain reaction (PCR) did not correlate with transmission of virus infection in vivo. PCR is an inappropriate test for evaluating the efficacy of disinfectant action despite its sensitivity. This in use method will allow testing of other decontamination procedures and their effectiveness on more complex surgical instruments.

Aim: 1) To determine the prevalence of hepatitis B in Sydney autopsies and 2) to determine the relationship between seroprevalence, hepatitis B risk factors and histological changes in the liver., Methods: One hundred autopsy subjects were studied for evidence of past or present hepatitis B infection, using RIA to detect the HBV antigens and antibodies in the serum and peroxidase-antiperoxidase technique to detect HBsAg and HBcAg in the liver. Both serum and liver were examined for the presence of HBV DNA., Results: Markers of hepatitis B virus infection were detected in either serum and/or liver of 29 subjects. Four subjects (4%) were seropositive for HBsAg. Eight subjects had been recently infected, 7 were chronically infected and 14 had recovered., Conclusion: The 29% prevalence of HBV infection is higher than expected. In four cases the serum was either free of HBV markers or showed conventional evidence of recovery, yet the liver still contained HBsAg. There were few histopathological changes despite the presence of HBsAg in the liver. The only epidemiological factors possibly predisposing to HBV infection were tattooing and drug abuse.

In 454 medical and dental students who were vaccinated against hepatitis B by means of a low dose (0.1 mL) of serum-derived vaccine, seroconversion rates of 27%, 70% and 89% were obtained after the first, second and third doses, respectively. These figures are comparable with the results that have been reported for the conventional intramuscular schedule, as were the final antibody titres. A fourth intradermal dose boosted the percentage of students who were protected from 82% to 87%. There was a significant variation in the response to different batches of vaccine. This study shows that the low-dose intradermal method is practicable and effective and can be used to achieve great economy in hepatitis B vaccination programmes. The possibility of adding hepatitis B to the present formula of triple antigen should be investigated as a way of extending hepatitis B vaccination to all infants in our community.

Risk factors associated with HBsAg carriers were prospectively examined in 1821 women attending the Antenatal Clinic of an inner-city obstetrics hospital. Of the sample, 3.2% were HBsAg carriers and 28.7% of 725 tested for anti-HBs were positive. Birth in a country where the prevalence of HBsAg is high and Aboriginal ancestry were the major associated factors rather than a past history of hepatitis or intravenous drug use. Women from Indochina or the Pacific region, if HBsAg-positive, were more likely than other carriers to have markers of viral replication including HBeAg, hepatitis B virus (HBV) DNA, and DNA polymerase. Evidence of past infection with HBV also varied with country of birth, but 11% of women with no apparent risk factors for prior HBV infection were anti-HBs positive. This study indicates the need for a screening programme for HBsAg in antenatal populations.

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.

Post-transfusion hepatitis developed in 2% of 842 cardiac-surgery patients surveyed in Sydney (4 cases per 1000 units of transfused blood). 3 of the 18 cases were caused by hepatitis B virus even though all units of blood which contained hepatitis B surface antigen (HBsAg) had been rejected. 1 case was caused by cytomegalovirus, and there were 14 (78%) cases of non-A, non-B hepatitis. A significantly higher proportion of the units of blood given to the patients in whom non-A, non-B hepatitis developed contained antibodies against both hepatitis B core antigen and HBsAg than the units of blood given to the other patients. Rejection of blood with these markers of past exposure to hepatitis B may reduce the incidence of post-transfusion non-A, non-B hepatitis by up to a half.

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.

Hepatitis B associated delta infection was found in Australian born narcotics users, patients with cirrhosis and hepatoma from Italy and Greece and in south east Asian immigrants. About 9% of patients with chronic hepatitis B were found to have intranuclear delta antigen in liver biopsies with immunofluorescence or anti-delta antibody in serum by radioimmunoassay. Delta may have been imported from southern Europe and Asia and a reservoir of delta infection may exist in narcotics users. Anti-delta was not found in hemophiliacs despite exposure to hepatitis B. Delta occurs in Australia and causes acute and particularly chronic hepatitis in addition to that caused by hepatitis B.

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 literature concerning hepatitis B in pregnancy is reviewed and problems of management of both the acute and chronic infections are discussed.

Hepatitis B core antigen (HBcAg) was prepared from human liver tissue and used in an immunoelectro-osmophoresis screening test to detect antibody to HBcAg (anti-HBc) in patients with evidence of liver disease and in blood donors. With the exception of two immunosuppressed HBsAg carriers, anti-HBc was found in all cases of hepatitis B infection even when HBsAg was detectable only by radioimmunoassay. Non-specific reactions were observed in 'non-B' hepatitis but, in spite of this problem, antib-HBc screening was considered a useful addition to routine tests in the clinical hepatitis laboratory.

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.

A prospective study of hepatitis in 20 dialysis units in the United Kingdom showed that the number of units with outbreaks increased from one in 1968 to three in 1969 and the overall attack rate rose from 1.7 to 5.3% in patients and from 0.5 to 1.3% in staff.In July 1969 a pilot study of patients' sera showed that all of the outbreaks were associated with Australia (Au) antigen. Au antigen was not detected in the unaffected units or in one unit in which there were several patients with abnormal liver function.In January 1970 systematic prospective testing for Au antigen was begun. Au antigen was detected in single patients in five more of the 20 units. The transfer of the affected patients to isolation for dialysis seemed to prevent the spread of infection in the units. The incidence of hepatitis in 1970 was 5.6% in patients and 0.4% in staff.