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Objective: Despite the remarkable progress in efforts to control disease spread, the nationwide elimination of hepatitis B in China is still hindered by the persistently high rate of hepatitis B virus (HBV) infection in Western China. This study aimed to evaluate the strategy of hepatitis B prevention and control in Western China and identify potential areas and strategies for improvement., Methods: Susceptible population vaccination, health education, professional training of doctors, and other prevention and control measures have been implemented in Wuwei city since 2010. Data were obtained from three representative cross-sectional serosurveys conducted in 2010, 2013, and 2015. The serum samples were subjected to enzyme-linked immunosorbent assays to detect the following seromarkers: HBV surface antigen (HBsAg), antibody against hepatitis B surface antigen (anti-HBs), and antibody against hepatitis B core antigen (anti-HBc). Estimates of variance were determined using Taylor series linearization methods., Results: The three serosurveys revealed decreases in the prevalence of HBsAg (7.19% in 2010 vs. 6.51% in 2013 vs. 5.87% in 2015) and anti-HBc positivity (43.89% vs. 32.87% vs. 28.46%) and an increase in the prevalence of anti-HBs positivity (49.07% vs. 53.66% vs. 53.72%) over time. From 2010 to 2015, the legally reported incidence of hepatitis B in Wuwei city decreased from 686.53/100,000 to 53.72/100,000. Notably, persistently high HBsAg-positive rates (above 5.40%) were observed among subjects aged 20-69 years old in the three serosurveys; the prevalence of HBsAg was above 1% among children younger than 10 years old. Furthermore, rural subjects had higher rates of HBsAg and anti-HBc positivity than their urban counterparts (6.04% vs. 4.83% and 30.26% vs. 20.35%, respectively) in 2015 but had a lower rate of anti-HBs positivity (49.68 vs. 55.18%). Multivariate regression analysis showed that age, urban and rural areas, and education level were the main factors affecting HBV infection., Conclusion: Although vaccine-based prevention and control measures reduced the rate of HBV infection in Wuwei City over time, the hepatitis B infection rate in children younger than 10 years was still higher than the national average level. Therefore, the prevention and control of mother-to-child transmission and the management of the infected should be the focus of future prevention and control work., (Copyright © 2020 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Over 90% of infants infected with hepatitis B virus (HBV) caused by mother-to-infant transmission will evolve to carrier status, and this cannot be prevented until widespread administration of the HB vaccine and hepatitis B immune globulin (HBIG) is implemented. This prospective study of 214 infants born to HBsAg-positive mothers was carried out to determine if either perinatal or intrauterine HBV transmission could be effectively prevented with HBIG and the HB vaccine. Peripheral blood was collected from mothers and from newborns before they received HBIG and the HB vaccine, as well as at 0, 1, 7, 24, and 36 months after birth. Infants born with an ratio of signal to noise(S/N) value of >5 for HBsAg (ABBOTT Diagnostic Kit) were defined as mother-to-infant transmission cases, those with an S/N between 5 and 50 were classified as perinatal transmission cases, and those with an S/N >50 were considered intrauterine transmission cases. Mother-to-infant transmission occurred in approximately 4.7% (10/214) of the infants; the perinatal transmission and intrauterine transmission rates were 3.7% (8/214) and 0.9% (2/214), respectively. The risk of mother-to-infant transmission increased along with maternal HBeAg or HBVDNA levels. After 36 months of follow-up, all perinatal cases became HBsAg-negative, whereas all intrauterine transmission cases evolved into carrier status. These results indicate that infants infected via intrauterine transmission cannot be effectively protected by HBIG and HB vaccine., (Copyright © 2011 Wiley-Liss, Inc.)

Objective: Our purpose was to explore the relationship between hepatitis B virus (HBV) gene heterogeneity and maternal vertical transmission., Methods: HBsAg-positive mothers and their neonates were selected and classified into a vertical infection neonate group (group N), a vertical infection mother group (group M) and a control group (group C). Serum HBsAg and HBeAg were examined. HBV gene fragments, including the pre-S1, and pre-S2 and S coding regions, were amplified and sequenced, and the genotype and serotype of the sequences were identified. Mutation sites and frequency of mutations were then compared between group N and group C., Results: A total of 104 HBV clone sequences were obtained. All obtained sequences belonged to genotype C and serotype adr. Upon comparing sequences between group N and group C, 4 nonsynonymous mutations were found with significant difference in mutation frequency (p < 0.05). When the mothers were both HBsAg and HBeAg positive, 10 nonsynonymous mutations were found. The frequencies of these mutations were significantly lower in group N than in group C (p < 0.05)., Conclusion: The 10 HBV mutations were negatively associated with vertical transmission when maternal HBeAg was positive. Furthermore, the species that were vertically transmitted to the fetus were mainly wild-type., (Copyright © 2010 S. Karger AG, Basel.)

Background and Aim: Hepatitis B virus (HBV) intrauterine transmission from infected mothers contributes significantly to the persistence of the high number of HBV carriers. The aim of this study was to identify potential risk factors for HBV intrauterine transmission., Methods: A case-control study was performed on pregnant women tested positive for HBsAg at Shaanxi Maternal and Neonatal Health Hospital, Xi'an, China, from September 2002 to October 2004. Serum samples were taken from infected women and their newborn infants and used for the detection of HBsAg. A structured standard questionnaire was used to collect demographic, medical and maternal data, and maternal HBV DNA, HBeAg, anti-hepatitis C virus and anti-hepatitis D virus were also assessed. Ten neonates validated as having HBV intrauterine transmission were selected as cases and others as controls., Results: The univariate analysis indicated that maternal HBeAg positivity (odds ratio [OR] = 5.96, 95% confidence interval [CI]: 1.61-22.12), HBV DNA positivity (OR = 12.09, 95% CI: 2.97-40.17) and sexual intercourse in the second trimester (OR = 9.15, 95% CI: 1.08-202.99) were significantly associated with an increased risk for HBV intrauterine transmission, whereas contraceptive measures before pregnancy (OR = 0.21, 95%CI: 0.04-0.99) were associated with a decreased risk. The multivariate analysis, however, identified maternal HBV DNA positivity (OR = 19.18, 95%: CI: 3.26-118.73) and sexual intercourse in the second trimester (OR = 1.29, 95%: CI: 1.00-1.66) as the only independent risk factors for HBV intrauterine transmission., Conclusions: The risk of HBV intrauterine transmission increased with increased frequency of sexual intercourse. Therefore, it is concluded that maternal HBV DNA positivity and sexual intercourse in the second trimester are independent risk factors for HBV intrauterine transmission.

There are many factors leading to intrauterine infection with hepatitis B virus (HBV). These factors include viral structure, HBV mutations, HBV DNA level, placenta barrier, immune status of the mother, and susceptibility of the fetus. The purpose of this study was to investigate the possible relationship between intrauterine infection with and HBV mutations of the genome of the virus. In this study, HBsAg-positive mothers were divided into two groups: intrauterine infection group and non-infection group according to whether the newborn infants were infected or not. The intrauterine infection group included four pairs of mother and their newborn infants infected in utero, and non-infection group included five HBsAg-positive mothers. HBV sequences from the two groups were analyzed and compared. The predominant strains in the mothers and infants from the intrauterine infection group were not completely consistent. This suggested that both HBV predominant strains and minority strains in the mothers could infect their infants through intrauterine transmission. Some HBV mutations probably related to intrauterine infection were examined and it was found that the frequencies of mutations were low in isolates of the virus of infants from the intrauterine infection group and high in the non-infection group. These results suggest that some strains of HBV from the mother may be transmitted selectively to the fetus in utero because of viral heterogeneity. The strains without screened mutations such as P21L in the pre-S1 region may infect the fetus more readily., ((c) 2005 Wiley-Liss, Inc.)

Objective: To establish a culture system of HBV positive serum infected Hep G2 cells in vitro., Methods: Hep G2 cells were seeded into six-well cluster dishes, at 1 x 10(-6) cells per well and incubated with 3 ml 10% fetal calf serum/ Dulbecco's modified Eagle's medium (10% FCS/DMEM) at 37 degrees in 5% CO2 air. At 24 h after plating, infection group Hep G2 cells were cultured with 0.5 ml HBV positive serum, in control group HBV negative serum was used, 24 h later the inoculums was removed. The cells were then extensively washed with 0.01 mol/L phosphate-buffered saline (PBS). After washing with PBS, 4 ml 2% FCS/DMEM were added to each well and the medium was collected every 12 h. ELISA method was used to detect HBsAg in culture medium. HBV DNA in cells and culture medium was detected by PCR., Results: In infection group, HBsAg could be detected from cell culture medium from 12 h (after PBS washed) to 84 h. HBV DNA could be detected by PCR in culture medium and cells., Conclusion: Infection of Hep G2 cells by HBV positive serum is feasible.

Previous studies reported that the HBV DNA level in maternal serum is an important risk factor for intrauterine infection. Two antiviral drugs, lamivudine (3TC) and interferon alpha (IFNalpha), are used extensively clinically to reduce maternal HBV DNA level, However, because of a lack of evidence on the efficacy and safety of these drugs during pregnancy, they are categorized as grade C which prevents their use during pregnancy. This study provides new data on the efficacy and safety of lamivudine and IFNalpha in HBV positive transgenic pregnant mice. In this study, transgenic mice with high titers of hepatitis B virus (HBV) were employed to study the antiviral effects of 3TC and IFNalpha during different gestation periods. The study also examined changes in several serological HBV markers, the effects of perinatal exposure to antiviral drugs on the mother and offspring, drug efficacy in reducing the level of HBV DNA in maternal blood, and the safety to both the mother and offspring. The main conclusion of the study is that a significant decrease in HBV DNA level can be obtained after treatment with lamivudine but not with IFNalpha. No adverse effects were observed in the maternal mice and the offsprings. This finding may provide a rationale for the potential use of lamivudine for the treatment of pregnant women as a safe and effective measure to reduce the level of maternal viremia., (Copyright 2005 Wiley-Liss, Inc.)

Objective: To observe the presence of hepatitis B virus (HBV) in first-trimester villi cells from pregnant women carrying HBsAg., Methods: Immunohistochemical streptavidin-biotin peroxidase complex (SABC) staining with monoclonal HBsAg, hepatitis B core antigen (HBcAg) and PCR, in situ hybridization were used for detection of HBV infection markers in villi. Positive villi ultramicrostructures were observed with transmission electron microscope., Results: HBV was detected in 8 of 25 villi of HBsAg positive pregnant women, the positive rate was 32%. HBsAg was located in the decidual cell, trophoblastic cell and villous mesenchymal cell. HBV analog was detected in rough endoplasmic reticulum of trophoblastic cell., Conclusions: HBV may infect villous cells in first-trimester pregnancy. It would be impossible for HBV to transmit the desmosomes.

Objective: To observe the efficacy and safety of lamivudine and interferon-alpha (IFN-alpha) therapy on decrease of serum hepatitis B virus (HBV) loading of HBV transgenic mice during pregnancy., Methods: Thirty-five transgenic mice replicating high levels of hepatitis B virus were randomly allocated into 5 groups, each of seven. Pregnant HBV transgenic mice in experimental groups 1 and 2 were given orally lamivudine [100 mg/(kg x d)] from pregnancy day 5 or 10 to delivery, mice in experimental groups 3 and 4 were given intramuscular (im) injection of IFN-alpha [5MU/(m(2) x 2d)], and mice in experimental group 5 were given normal saline at the same times. The changes of serum HBsAg, HBV DNA before and after the treatment were detected. At the same time, eighteen C57BL/6J female mice (clean level) were randomly allocated into control groups 1, 2 and 3 (each group of six), which were given lamivudine, IFN-alpha and saline respectively (the dosage was the same as that of experimental groups). The safety indexes of pregnant mice, fetus and newborns in experimental groups and control groups were observed., Results: (1) The changes of serum HBsAg titers: The average serum HBsAg titers from mice in experimental group 1 were lowered significantly from (166 +/- 98) ng/ml to (82 +/- 59) ng/ml after drug treatment (P < 0.05). Those from mice in experimental group 2 were also reduced from (159 +/- 49) ng/ml to (82 +/- 60) ng/ml after drug treatment, but there was no significant difference between before and after the treatment (P > 0.05). There was no significant difference in serum HBsAg between before and after the treatment in other groups (P > 0.05). (2) The changes of HBV DNA titers: The serum HBV DNA titers from mice in experimental groups 1 and 2 were significantly decreased, from (5.50 +/- 0.86) copies/ml to (2.58 +/- 2.01) copies/ml, with significant difference between before and after the treatment (P < 0.01). Those from mice in experimental groups 3 and 4 were reduced from (5.55 +/- 0.24) copies/ml to (5.46 +/- 0.45) copies/ml, without significant difference between before and after the treatment (P > 0.05). The serum HBV DNA titer from mice in experimental group 5 was not different between before and after the treatment (P > 0.05). (3) Observation of safety indexes: no evidence in toxicity were observed in mice from experimental groups and control groups. No significant abnormalities of live fetus were observed. The postnatal survival and weight of live pups were not different between the groups (P > 0.05). (4) Comparison of the rate of dead fetus and the rate of maternal dead fetus: The rate of dead fetus and the rate of maternal dead fetus from mice in experimental groups 1 and 2 were 8.3% and 50.0% respectively, those from mice in experimental groups 3 and 4 were 8.2% and 66.7% respectively, and those from mice in experimental group 5 were 9.7% and 66.7%. There was no significant difference in the rate of dead fetus and the rate of maternal dead fetus from mice between the groups (P > 0.05)., Conclusions: Effective lamivudine treatment during gestation can reduce hepatitis B viremia in pregnant HBV transgenic mice, thus lowering the risk of intrauterine infection. It has no significant adverse effect on safety of pregnant mice and their offspring.

Objective: Case-control study was employed to explore the association of sexual behavior during pregnancy and hepatitis B virus (HBV) intrauterine infection., Methods: 212 HBsAg positive pregnant women were consecutively collected and investigated as objects. Those neonates detected for HBsAg with S/N value > or = 5 by Abbott reagents in periphery sera were selected as cases, others as controls. Information on sexual behavior during pregnancy, maternal HBeAg status and other factors was collected, and were analyzed with univariate analysis, multivariate logistic regression analysis, etc, to explore the association of factors with HBV intrauterine infection., Results: Ten of the 214 neonates were validated as occurrence of HBV intrauterine infection. Sexual behavior in the second trimester during pregnancy, with odd ratios 9.15 (95% CI: 1.10 - 76.28), as well as maternal positivity for HBeAg and HBV DNA, was significantly associated with HBV intrauterine infection, and sequently affirmed by multiple logistic regression analysis. The strength of association increased with frequency of sexual behavior. Interaction analysis suggested that there was synergistic interaction between maternal positivity of HBeAg and sexual behavior in the second trimester., Conclusion: Sexual behavior was a newly discovered risk factor for HBV intrauterine infection, which need to be estimated in future studies. Inhibition of virus replication and moderate control of sexual behavior would be helpful to prevent HBV intrauterine infection.

Intrauterine hepatitis B virus (HBV) infection has been suggested to be caused by transplacental transmission that cannot be blocked by hepatitis B vaccine. This would decrease the effectiveness of hepatitis B vaccine. This study examined the risk factors and mechanism of transplacental HBV transmission. A case-control study included 402 newborn infants from 402 HBsAg-positive pregnant women. Among these, 15 newborn infants infected with HBV by intrauterine transmission were selected as cases, and the rest as controls. A pathology study included 101 full-term placentas from the HBsAg-positive pregnant women above and 14 from HBsAg-negative pregnant women. Immunohistochemistry staining and HBV DNA in situ hybridization were used to estimate the association of intrauterine HBV infection and HBV infection in the placentas. HBeAg positivity in mothers' sera (OR = 17.07, 95%CI 3.39-86.01) and threatened preterm labor (OR = 5.44, 95%CI 1.15-25.67) were found to be associated with transplacental HBV transmission. The intrauterine infection rate increased linearly and significantly with maternal serum HBsAg titers (trend test P = 0.0117) and HBV DNA concentration (trend test P < 0.01). Results of the pathology study showed that HBV infection rates decreased gradually from the maternal side to the fetal side (trend test P = 0.0009) in the placental cell layers. There was a significant association between intrauterine HBV transmission and HBV infection in villous capillary endothelial cells (VCEC) in the placenta (OR = 18.46, P = 0.0002). The main risk factors for intrauterine HBV infection are maternal serum HBeAg positivity, history of threatened preterm labor, and HBV in the placenta especially the villous capillary endothelial cells. Previous reports of transplacental leakage of maternal blood causing intrauterine infection are confirmed. In addition, there appears to be a "cellular transfer" of HBV from cell to cell in the placenta causing intrauterine infection. This latter hypothesis needs to be confirmed., (Copyright 2002 Wiley-Liss, Inc.)