Surface Antigen Carrier State Research Articles

Maternal hepatitis B surface antigen Carrier Status and Pregnancy Outcome: A Retrospective Cohort Study.

AbstractTo investigate the effect of maternal hepatitis B surface antigen (HBsAg) carrier status during pregnancy on pregnancy outcomes in a population of patients in Hangzhou, China. A retrospective cohort study was conducted to analyse data from 20 753 pregnant women who delivered at Hangzhou Women's Hospital between January 2015 and March 2020. Of these, 18 693 were normal pregnant women (the non-exposed group) and 735 were HBsAg carriers (the exposed group). We then analysed by binary multivariate logistic regression to determine the association between maternal HBsAg-positive and adverse pregnancy outcomes. The prevalence of HBsAg carriers was 3.78% and the odds ratio (OR) for maternal age in the exposed group was 1.081. Pregnant women who are HBsAg-positive in Hangzhou, China, are at higher risk of a range of adverse pregnancy outcomes, including intrahepatic cholestasis of pregnancy (ICP) (adjusted OR (aOR) 3.169), low birth weight (aOR 2.337), thrombocytopenia (aOR 2.226), fallopian cysts (aOR 1.610), caesarean scar pregnancy (aOR 1.283), foetal distress (aOR 1.414). Therefore, the obstetricians should pay particular attention to ICP, low birth weight, thrombocytopenia, fallopian cysts, caesarean scar, foetal distress in HBsAg-positive pregnant women.

Maternal hepatitis B surface antigen carrier status and its impact on neonatal outcomes: a cohort study of 21 947 singleton newborns in China

Objective: To explore the impact of maternal hepatitis B surface antigen (HBsAg) carrier status on neonatal outcomes.Methods: A retrospective cohort study was conducted using data from medical records database of six hospitals in China. Information on maternal characteristics and selected neonatal outcomes was retrieved for all women who delivered singleton infants between 1 January 2009 and 31 December 2010.Results: A total of 21 947 singleton newborns and their mothers were included. The prevalence of maternal HBsAg positivity was 4.2% (95% confidence interval (CI) 3.9–4.5%). Compared with infants born to HBsAg-negative women, infants born to HBsAg-positive mothers were more than twice more likely to have a malformation before (adjusted odds ratio (aOR) 2.23, 95% CI 1.15–4.30) and at birth (aOR 2.66, 95% CI 1.38–5.14), but were less likely to be macrosomia (aOR 0.67, 95% CI 0.47–0.96). No statistically significant association was found between maternal HBsAg positivity and preterm birth (aOR 1.20, 95% CI 0.95–1.51), low birth weight (aOR 1.24, 95% CI 0.91–1.69), and Apgar scores at 1 min (aOR 0.88, 95% CI 0.49–1.57) and 5 min (aOR 1.84, 95% CI 0.89–3.81).Conclusion: Maternal HBsAg positivity may be associated with a higher risk of congenital malformation.

Magnitude of asymptomatic hepatitis B virus surface antigen carrier state in voluntary blood donors: Predonation screening and gender considerations

Context: Safety of blood transfusion. Aims: The study was conducted to assess the overall prevalence of hepatitis B surface antigen (HBsAg) in blood donors (BDs), to know the gender differences in prevalence and to understand the implications. Settings and Design: Blood bank of a tertiary care hospital. Observational study. Materials and Methods: Data of 17,976 voluntary BDs who donated blood between January 2006 and December 2012 was evaluated. Fresh serum samples of all BDs were screened for HBsAg using HEPALISA (3 rd generation ELISA method, manufactured by J. Mitra & Co. Pvt. Ltd., New Delhi, India). Statistical Analysis Used: Statistical analysis was performed using the Chi-square test, df and P value. Results: Totally 17,976 BDs were studied, of which 16,972 (94.4%) were males and 1,004 (5.6%) were females. The male to female ratio was 16.8:1. Among HBsAg-positive BDs, 230 (98.7%) were males and 3(1.3%) were females. The HBsAg prevalence was - overall 1.3%, males - 1.3%, females - 0.29%. The difference in prevalence of HBsAg in males and females was statistically significant (χ2 = 8.29, df = 1, P = −0.004). The rate of HBsAg positivity showed a slight decline over last 5 years. Conclusions: The study region has a low prevalence for HBsAg. Low prevalence in women makes them better donors; hence they could be encouraged to donate blood voluntarily. Increase in proportion of women in BDs can minimize transmission of hepatitis B virus by transfusion.

Age-Related Macular Degeneration: Prevalence and Risk Factors from Korean National Health and Nutrition Examination Survey, 2008 through 2011

To investigate the prevalence and risk factors of age-related macular degeneration (AMD) in the Korean population. A cross-sectional study using a complex, stratified, multistage, probability-cluster survey, which can produce nationally representative estimates. Using the database of Korean National Health and Nutrition Examination Survey from 2008 through 2011, 14 352 participants 40 years of age or older with gradable fundus photographs were included. Age-related macular degeneration was determined by fundus photograph. Prevalences of AMDs were estimated. Risk factor analyses were conducted using logistic regression analyses (LRAs). Prevalence and risk factors of AMD. The prevalence of AMD was 6.62% (95% confidence interval [CI], 6.15%-7.09%) in the Korean population: 6.02% (95% CI, 5.56%-6.48%) were early AMD and 0.60% (95% CI, 0.45%-0.75%) were late AMD. The prevalence of early AMD in women (6.73%; 95% CI, 6.11%-7.35%) was higher than that in men (5.25%; 95% CI, 4.61%-5.89%; P<0.001), and the prevalence of late AMD in women (0.37%; 95% CI, 0.22%-0.52%) was lower than that in men (0.85%; 95% CI, 0.59%-1.12%; P<0.001). However, in multiple LRAs both early and late AMD had no association with gender, house income, residence, sun exposure, or systemic comorbidities, including hypertension, diabetes mellitus, and cardiovascular diseases. Early AMD had positive associations with older age groups (P<0.001), lower education (P = 0.027), occupation (P<0.001), anemia (P = 0.027), hepatitis B surface antigen carrier status (P<0.001), not being overweight (body mass index [BMI], P = 0.032; waist circumference, P = 0.041, in separate analyses), and higher serum high-density lipoprotein (HDL) level (P = 0.046), but not with smoking status. Late AMD had positive associations with age groups (P<0.001), current smokers (P = 0.022), and lower BMI (P = 0.037). The results suggest that there are 1.21 million individuals with early AMD and 121 000 individuals with late AMD in Korea. Nonoverweight status and higher HDL levels, generally assumed as positive health indicators, as well as anemia and hepatitis B infection had harmful associations with AMD in our study, implying a possible different pathophysiologic process of AMD in Asians compared with that of white persons.

Correlation between maternal hepatitis B surface antigen carrier status with social, medical and family factors in an endemic area: have we overlooked something?

Hepatitis B virus (HBV) infection is endemic in many countries, but the risk factors for HBV carriage in the obstetric population are unclear. A survey on 1,580 women attending the antenatal clinic in an endemic region was conducted in order to examine the prevalence of and factors associated with maternal HBV carriage, including socio-demographic, medical, and previous obstetrical and family history, by means of a questionnaire. The prevalence of maternal HBV carriage was 9.1%, and 4.8% of women with a history of hepatitis B vaccination were found to be HBV carriers. Factors associated with maternal HBV carriage were residency status (adjusted odds ratio [aOR] 3.65 for immigrants; aOR 7.62 for non-residents), positive family history (aOR 3.72 for infected mother; aOR 5.36 for other family members), no previous vaccination (aOR 4.39) and having previous HBsAg testing (aOR 2.26). The findings suggest that there was probably an overlooked role of horizontal transmission within the family setting in addition to perinatal transmission in determining the likelihood of HBV infection in our obstetric population. Reconfirmation of hepatitis B status might be necessary among individuals with a history of vaccination to ensure the effectiveness of their immunoprotection.

Extra Renal Manifestations Of Acute Hepatitis “B” Virus Infection

Approximately 400 million people are chronic HBV carriers worldwide. The spectrum of chronic HBV infection ranges from asymptomatic hepatitis B surface antigen carrier state to chronic hepatitis with progression to cirrhosis and end-stage liver disease and carcinoma of liver. Several extrahepatic syndromes are associated with acute HBV infection like serum sickness reaction, polyarteritis nodosa due to ischemia of vasa nervosum of the nerves and glomerulonephritis. We present here the a case of a 38-year male with end stage renal disease due to diabetic nephropathy on maintenance haemodialysis with acute hepatitis B virus infection with extra hepatic, extra renal immunological manifestations.

Sexual transmission is associated with spontaneous HCV clearance in HIV-infected patients

There are conflicting data regarding the incidence and factors implicated in the spontaneous clearance of hepatitis C virus (HCV) after acute infection. The aim of this study was to determine the epidemiological factors that predict the resolution of acute HCV infection without therapy in patients with human immunodeficiency virus (HIV) infection. We conducted a retrospective, multivariate analysis of epidemiological data from HIV-infected patients presenting from 2000 to 2007 with evidence of past or present HCV infection. Data were collected from one American and two European HIV treatment clinics. A final cohort of 769 HIV-infected patients referred for treatment with available test results for antibody to HCV, HCV RNA, and hepatitis B surface antigen were included for the analysis. We calculated spontaneous clearance rates based on race, geographical location, gender, transmission risk factors, and hepatitis B virus coinfection. Patients who admitted to a history of injection drug use spontaneously cleared the HCV infection significantly less often (11.6%) than those in whom sexual transmission was the presumed route of HCV infection (21.9%) (p=0.004). This difference was more pronounced when heterosexual contact as the source of infection was analyzed separately. Multivariate analysis identified heterosexual HCV transmission (OR 2.81, 95% CI 1.55-5.09) and hepatitis B surface antigen carrier status (OR 10.3, 95% CI 4.29-24.73) as independent factors predicting spontaneous HCV clearance. No differences according to gender, race or geographical origin were observed. In summary, sexual transmission, particularly heterosexual, and hepatitis B virus coinfection were the only factors associated with spontaneous HCV clearance in this HIV-infected population.

Hepatitis B in children

We read with interest the special article by Shneider et al.1, which was published in November 2006, but related to a conference held in March 2006. As regards hepatitis B, Shneider et al. state: “Unfortunately at present there are inadequate numbers of patients with sufficiently long follow-up to give an accurate assessment of the lifelong risk and/or predictors of serious morbidity and mortality in children with chronic hepatitis B”, and “it is nearly impossible to assess an accurate risk of development of HCC before the age of 20 years in children with HBV infection acquired early in life.” We believe that our 29-year longitudinal study of chronic hepatitis B in 99 otherwise healthy children, published in March 2006,2 and commented on in Hepatology Highlights of April 2006,3 can give some answers with regard to the prognosis of chronic hepatitis in children infected postnatally early in life. Pediatric HBV infection is often identified with the Chinese model of vertical transmission and tolerance to the virus. However, in many areas of the world, including Southern Europe before compulsive HBV vaccination and Eastern Europe, children are preferably infected postnatally and do not develop tolerance. In this latter model of infection, the outcome within the first 20 years of life is benign (inactive hepatitis B surface antigen carrier state) in the vast majority of cases, although 2 patients in our cohort developed HCC and are long-term survivors after surgery. It is certainly true that life-long risks remain undefined, and environmental factors can change the prognosis at any time, but 3 decades of follow-up have covered at least the gap between the natural history of hepatitis B in children and in young adults in our endemic area. Flavia Bortolotti M.D.*, Maria Guido M.D. , * Department of Clinical and Experimental Medicine, University of Padua, Padova, Italy, Department of Pathology, University of Padua, Padova, Italy.

Compliance with antenatal screening for hepatitis B surface antigen carrier status in pregnant women and consecutive procedures in exposed newborns.

The goal of this study was to determine compliance with official recommendations for prevention of perinatal hepatitis B virus transmission from hepatitis B surface antigen (HBsAg) positive mothers to their offspring. All infants born to HBsAg positive mothers at the University Women's Hospital in Basel, Switzerland, in 2001 were identified and post-exposure immunisations were analysed. In addition, detailed written information on subsequent hepatitis B immunisations was obtained from the infants' paediatricians. A total of 1513 women gave birth to 1554 children and screening for HBsAg had been performed in 1503 (99%) women, of whom 8% were screened during delivery. A group of 18 (1.2%) women were HBsAg positive and 17 (95%) of the 19 exposed infants promptly received active and passive immunisation. One exposed infant was lost to follow-up and in one, postnatal vaccination was missed. Of the remaining 17 exposed infants, 9 (53%) received the full course of three active immunisations, but only two (12%) were immunised within the recommended time frame. On follow-up, six children were still too young for serological testing for successful immunisation. Among the remaining 11 immunised infants, serological testing had been performed in 4 (36%). Compliance with recommendations for hepatitis B surface antigen screening was excellent in this study. The proportion of exposed infants receiving all three active immunisations was satisfactory, but more attention must be paid to complete and timely administration and serological testing in the future. This will require improved communication between neonatology units and care-providing paediatricians in private practices.

Significance of hepatitis B viremia levels determined by a quantitative polymerase chain reaction assay in patients with hepatitis B e antigen–negative chronic hepatitis B virus infection

Objectives In hepatitis B e antigen (HBeAg)-negative chronic hepatitis B virus (HBV) infection, the clinical relevance of low viremia levels remains unclear. We evaluated the clinical significance of a single baseline serum HBV DNA measurement by a quantitative polymerase chain reaction (PCR) assay in this setting. Methods In total, 196 patients with HBeAg-negative chronic HBV infection (62 inactive carriers, 134 with chronic hepatitis B) were studied. ALT activity was normal at baseline in 25/134 HBeAg-negative chronic hepatitis B patients (18.7%), whereas it remained normal throughout follow-up in all inactive carriers. Results HBV DNA was <30,000 copies/ml in 14 (10.5%) and <100,000 copies/ml in 17 (12.9%) HBeAg-negative chronic hepatitis B patients, whereas it was <30,000 copies/ml in all inactive carriers (undetectable in 14). In particular, HBV DNA levels were <100,000 copies/ml in eight (32%) and <30,000 copies/ml in five (20%) of the 25 patients with HBeAg-negative chronic hepatitis B and normal baseline ALT values. HBV DNA levels with a cut-off at 30,000 or 100,000 copies/ml could correctly classify 92.9% or 91.3% of patients with HBeAg-negative chronic HBV infection, whereas ALT or IgM anti-HBc (IgM class antibody to HBV core antigen) index > 0.200 could correctly classify only 87.2% and 82.1% of patients, respectively. A combined HBV DNA and IgM anti-HBc index performed better by correctly classifying 94.4% of cases. Conclusions Serum HBV DNA levels evaluated by sensitive quantitative PCR assays can be used for differentiation between HBeAg-negative chronic hepatitis B and inactive hepatitis B surface antigen carrier state, but the cut-off level should be set at approximately 30,000 copies/ml and certainly lower than the recently suggested level of 100,000 copies/ml.

Hepatitis B surface antigen carrier status and its correlation to gestational hypertension.

To determine whether chronic hepatitis B surface antigen (HBsAg) carrier status is associated with an increased incidence of gestational hypertension. A retrospective analysis of all deliveries in a regional obstetric unit over a 4-year period using a comprehensive obstetric database. The data of 13,792 patients were analysed, of which 1340 (9.71%) were chronic HBsAg carriers. Contrary to our hypothesis, the overall incidence of gestational hypertension was significantly lower in the HBsAg positive group (2.01%) as compared to the negative group (3.58%) (P < 0.01, odds ratio (OR) 0.55, 95% confidence interval (CI) 0.37-0.81). When comparing the incidence of severe preeclampsia, the difference remained significant (0.22 and 0.79%, respectively, P < 0.05, OR 0.28, 95% CI 0.08-0.88). There was otherwise no difference in the incidence of other major obstetric complications between the HBsAg positive and negative groups. The findings presented did not support a positive association between HbsAg carrier status and gestational hypertension. The data from the present study, and re-evaluation of similar published data, in fact suggest the contrary observation of a lower than normal incidence of gestational hypertension in HbsAg positive mothers.

Recommended Childhood Immunization Schedule—United States, January–December 1999

The annual Recommended Childhood Immunization Schedule of the American Academy of Pediatrics (AAP), the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC), and the American Academy of Family Physicians (AAFP) is issued in January of each year. Several significant changes for the 1999 Schedule have been made since publication of the 1998 Schedule.1This report provides the 1999 Schedule and delineates the changes, including those in the footnotes, as follows:1. Rotavirus vaccine (Rv) at 2, 4, and 6 months of age is recommended. Details of the AAP recommendations for rotavirus vaccination were published in the December 1998 issue ofPediatrics.2 Rv is shaded in theSchedule to indicate that implementation of the recommendation for routine use will require reconciliation of related economic issues, as noted in the AAP statement.2. Inactivated poliovirus vaccine (IPV) is recommended at 2 and 4 months of age. For the third and fourth doses of poliovirus vaccine, either IPV or oral poliovirus vaccine (OPV) can be administered. Details of the AAP recommendations regarding this change are given in the statement in this issue of Pediatrics.33. The manufacturer of Recombivax HB (Merck and Co, Inc, West Point, PA) has standardized the dose of this hepatitis vaccine to 5 μg for children from birth through 19 years of age regardless of maternal hepatitis B surface antigen carrier status. The change was made to avoid the confusion that occasionally occurred due to the availability of multiple dose formulations of this vaccine product. Children who have received a 2.5-μg dose of Recombivax for any or all the recommended doses are considered adequately immunized and no additional doses need to be administered. The other available hepatitis B vaccine, Engerix B (SmithKline Beecham, Pittsburgh, PA), also has a standard dose (10 μg) for all children from birth through 19 years of age. The vaccines are interchangeable when given in the doses recommended by the manufacturers.4. Acellular pertussis vaccines combined with diphtheria and tetanus toxoids (DTaP) are listed on the Schedule as the recommended product for pertussis vaccination. Whole-cell pertussis-containing vaccines (DTP) remain acceptable, as noted in the footnote.A fourth acellular pertussis-containing vaccine (Certiva [North American Vaccines, Beltsville, MD]) has been approved by the Food and Drug Administration (FDA) for immunization of infants and children. Clinical data to support the superiority of one DTaP product in comparison to the others are not available, and therefore the four approved DTaP products are considered equally acceptable. Additional questions regarding acellular pertussis vaccines have been addressed in a recent article in AAP News.45. The footnote in the Schedule pertaining toHaemophilus influenzae type b (Hib) vaccine has been modified to indicate that currently available DTaP/Hib combination products should not be used for the primary immunization series of infants unless approved by the FDA for the specific ages. The use of one such product in infants has resulted in suboptimal antibody responses.56. Minor changes to clarify recommendations have been made in the measles–mumps–rubella vaccine (MMR) and varicella footnotes, and the numbers (1, 2, and 3) for the respective doses of hepatitis B vaccine in the Schedule have been omitted to make the information consistent with that for other vaccines.Detailed recommendations for the use of the vaccines routinely indicated during infancy, childhood, and adolescence are given in the1997 Red Book,6 AAP statements (www.aap.org), and ACIP statements (www.cdc.gov/nip) on specific vaccines, and the respective manufacturers' package inserts.

Role of hepatitis C and delta viruses in the termination of chronic hepatitis B surface antigen carrier state: a multivariate analysis in a longitudinal follow-up study.

Influences of hepatitis delta (HDV) or C virus (HCV) superinfection on the spontaneous clearance of hepatitis B virus (HBV) surface antigen (HBsAg) were investigated in 992 patients. Patients were infected with HBV alone (group 1), HBV and HDV (group 2), HBV and HCV (group 3), or all three viruses (group 4). They were followed for 6.2 +/- 3.7 years. Thirty-six patients (3.6%) had spontaneous serum HBsAg clearance. There was an increasing linear trend in the annual incidence from 0.43% (group 1) to 0.64% (group 2), 2.08% (group 3), and 2.33% (group 4; P < .0001). Relative risk (RR) of group 3 to 1 was 4.8 (P < .001) and of group 4 to 1 was 5.1 (P < .02). RR was significantly higher in group 3 than 2 (P < .02). By Cox multivariate regression analysis, only HCV superinfection and age at entry were significant influencing factors. Moreover, there was a significant interaction between HCV and age. Patients > 35 years old with HCV had a higher HBsAg clearance rate. Results suggest that HCV is the most important hepatotropic virus that enhances HBsAg clearance in chronic hepatitis B.

Prevalence of Hepatitis B Surface Antigenemia Among Patients withSchistosoma mansoni

Prevalence of Hepatitis B Surface Antigenemia Among Patients withSchistosoma mansoni

Routine screening for hepatitis B in an obstetric population

A prospective study was performed to determine whether the Centers for Disease Control (CDC) risk factors for hepatitis B are reliable predictors of the hepatitis B surface antigen carrier state in an obstetric population. At their initial obstetric visit, 1466 consecutive patients had their serum screened for hepatitis B surface antigen by radioimmunoassay. During the initial interview, the physician obtained information regarding the presence of any of the CDC risk factors for hepatitis B (ethnicity or history of venereal disease, blood transfusion, hepatitis exposure, hepatitis, drug abuse, or occupational exposure). Twelve women were found to have positive hepatitis B surface antigen, for a prevalence of 0.82%. Six of these 12 had risk factors. Five had high-risk ethnic background, two of whom also had a history of hepatitis. One health care worker, a nurse, was also positive for hepatitis B surface antigen. The other six patients had no recognized risk factors. If hepatitis B surface antigen had been evaluated according to the CDC risk-factor guidelines, half of hepatitis B surface antigen-positive patients would not have been identified.

Natural history of acute hepatitis B surface antigen-positive hepatitis in Greek adults

We prospectively followed up 821 adults with acute viral hepatitis hospitalized at the Athens Hospital for Infectious Diseases between May 1981 and May 1983. Radioimmunoassays for the detection of serologic markers of hepatitis A virus, hepatitis B virus, and hepatitis δ virus, and molecular hybridization techniques for the detection of serum hepatitis B virus deoxyribonucleic acid and hepatitis δ virus ribonucleic acid were used. Based on the results of an enzyme immunoassay for the detection of immunoglobulin M antibody to hepatitis B core antigen (Corzyme-M), 563 cases were diagnosed as acute hepatitis B and 45 as acute hepatitis superimposed on hepatitis B surface antigen carriage. Development of the hepatitis B surface antigen carrier state was observed in only 1 (0.2%) of the 507 cases with acute hepatitis B that were followed. In contrast, hepatitis B surface antigen persisted in all the latter cases. Acute hepatitis superimposed on hepatitis B surface antigen carriage was attributed to (a) hepatitis A virus superinfection in 2 (4.4%), (b) hepatitis δ virus superinfection in 22 (48.9%), (c) reactivation of chronic type B hepatitis in 12 (26.7%), (d) seroconversion from hepatitis B e antigen-positive to anti-hepatitis B e antibody-positive in 2 (4.4%), (e) presumed superinfection by non-A, non-B agent(s) in 6 (13.4%), and (f) the first clinical manifestation of chronic active hepatitis in 1 (2.2%) case. These data show that (a) acute clinical hepatitis B in adults seems to be a self-limited disease and rarely leads to the development of the carrier state in this epidemiologic setting and (b) hepatitis δ virus superinfection and spontaneous reactivation of chronic hepatitis B are the principal causes of acute hepatitis superimposed in hepatitis B surface antigen carriers in an area with a moderately high prevalence of hepatitis B virus infections.

Selected infectious disease risks in international adoptees.

In 1985 there were approximately 8500 international adoptions in the United States, a phenomenon that has doubled in the past 5 years. The majority of these children originate from areas of the world where the hepatitis B virus is hyperendemic and where the prevalence of numerous other infectious diseases is higher than it is domestically. We consecutively screened 360 adopted Korean children for hepatitis B virus markers, syphilis serology, tuberculin status and the presence of parasitic infection. Ten hepatitis B virus carriers were identified (prevalence, 2.8%) as were two children with congenital syphilis and two with reactive tuberculin skin tests. Intestinal parasitosis was not evident but four cases of scabies were detected and were associated with prior residence in an orphanage. We conclude that even though the seroprevalence rate was lower than expected, providers responsible for the care of Korean adoptees should screen for the hepatitis B surface antigen carrier state, that susceptible household contacts of hepatitis B surface antigen-positive children should be protected with hepatitis B vaccine and that children treated abroad for congenital syphilis should be assessed for the adequacy of therapy.

Transgenic mouse models for the chronic hepatitis B surface antigen carrier state: Transfection a deux

In an attempt to establish a model of the healthy carrier state in hepatitis B virus (HBV) infections, transgenic mice expressing HBV genes were produced. Fertilized one-cell eggs were microinjected with subgenomic fragments of HBV DNA containing the coding regions for the HBV surface antigen (HBsAg) and pre-S and×antigens. Either the normal (HBV) or metallothionein promoters were used to obtain expression of the HBV genes. There was no evidence of viral replication or tissue pathology. The integrated HBV DNA sequences were inherited in a normal Mendelian fashion. Three of 16 transgenic mice expressed HBV-encoded gene products to which they were immunologically tolerant. Expression was not tissue specific and may be influenced by the genomic integration site and cellular factors. Both HBsAg and pre-S antigen were detectable within the cytoplasm of hepatocytes and renal tubular epithelial cells. High serum concentrations of HBsAg were detectable and the secreted product appeared authentic as judged by mean density, morphology, mean particle diameter, polypeptide composition, and antigenicity. The absence of tissue pathology in these immunologically tolerant animals supports the hypothesis that cellular injury under these conditions is not a direct consequence of expression of the pre-S or HBs regions of the HBV genome. Two transgenic mice were obtained that contain in their chromosomes the complete hepatitis B virus (HBV) genome except for the core gene. These mice secrete particles of HBV surface antigen (HBsAg) in the serum. In one mouse, HBV DNA sequences that had integrated at two different sites were shown to segregate independently in the first filial generation (F1) and only one of the sequences allowed expression of the surface antigen. Among these animals the males produced five to ten times more HBsAg than the females. A 2.1-kilobase messenger RNA species comigrating with the major surface gene messenger RNA is expressed specifically in the liver in the two original mice. The results suggest that the HBV sequences introduced into the mice are able to confer a tissue-specific expression to the S gene. In addition, the HBV transgenic mice represent a new model for the chronic carrier state of hepatitis B virus infection.

A transgenic mouse model of the chronic hepatitis B surface antigen carrier state.

In an attempt to establish a model of the healthy carrier state in hepatitis B virus (HBV) infections, transgenic mice expressing HBV genes were produced. Fertilized one-cell eggs were microinjected with subgenomic fragments of HBV DNA containing the coding regions for the HBV surface antigen (HBsAg) and pre-S and X antigens. Either the normal (HBV) or metallothionein promoters were used to obtain expression of the HBV genes. There was no evidence of viral replication or tissue pathology. The integrated HBV DNA sequences were inherited in a normal Mendelian fashion. Three of 16 transgenic mice expressed HBV-encoded gene products to which they were immunologically tolerant. Expression was not tissue specific and may be influenced by the genomic integration site and cellular factors. Both HBsAg and pre-S antigen were detectable within the cytoplasm of hepatocytes and renal tubular epithelial cells. High serum concentrations of HBsAg were detectable and the secreted product appeared authentic as judged by mean density, morphology, mean particle diameter, polypeptide composition, and antigenicity. The absence of tissue pathology in these immunologically tolerant animals supports the hypothesis that cellular injury under these conditions is not a direct consequence of expression of the pre-S or HBs regions of the HBV genome.

Hepatitis B Surface Antigen Carrier State in Neonates

Acute type B viral hepatitis developed near the term of pregnancy in seven women. All had signs of acute hepatitis at delivery, and hepatitis B surface antigenemia persisted two to four weeks after delivery. Two milliliters of conventional immune human serum globulin was administered to the neonates within a week of birth, after preexisting type B viral hepatitis infection was excluded. The antibody against hepatitis B surface antigen (anti-HBs) content of two of the administered batches of immune human serum globulin was 1:32 and 1:64. None of the babies became hepatitis B surface antigen carriers, and anti-HBs developed without obvious clinical hepatitis in one baby. Conventional immune human serum globulin in larger doses may be a relatively safe and effective prophylaxis against the development of hepatitis B surface antigen carrier state even if the anti-HBs content in the administered dose is relatively small.