Hepatitis B Virus Mother-to-child Transmission Research Articles

Chronic Hepatitis B in Women of Childbearing Age and Pregnant Women in China: A Cross-Sectional Study.

Pregnant women and women of childbearing age were enrolled in our study and their knowledge about the Hepatitis B virus (HBV) and chronic hepatitis B (CHB) was evaluated. A questionnaire was distributed to every woman in the cross-sectional study. The questionnaire was answered by all participants before they received health education and advice about HBV and CHB from the doctors visited. Data collected from all answers were analyzed using the χ2 test and logistic regression models. A total of 206 pregnant women and women of childbearing age with CHB infection were enrolled in the study during their first visit to the Infectious Diseases Clinic of the Third Affiliated Hospital of Guangzhou Medical University. Some women of childbearing age (40.8%) and pregnant women with CHB infection (30.6%) still believed HBV could be transmitted through diet and/or mosquito bites. Some women of childbearing age and pregnant women with CHB infection had limited knowledge of the prevention of HBV transmission (111 of 206, 53.9%). Women with higher levels of education had more knowledge about HBV (senior middle school, P = 0.02; university, P <0.01). The majority of participants were willing to take antiviral medicine to decrease the mother-to-child transmission (MTCT) rate of HBV. Some women of childbearing age and/or pregnant women with CHB infection have relatively limited knowledge about HBV or CHB. This situation contributes to the timeliness, or lack thereof, of these women with CHB to see a doctor and receive antiviral therapy. As a result, the morbidity and mortality of HBV-related complications could increase along with the rate of MTCT of HBV.

Effectiveness and Safety of Tenofovir Alafenamide Fumarate in the Prevention of Perinatal Hepatitis B Transmission: A Meta-Analysis.

This study aimed to assess the effectiveness and safety of tenofovir alafenamide fumarate (TAF) in the prevention of mother-to-child transmission (MTCT) of hepatitis B virus (HBV). We performed a meta-analysis of studies from the Cochrane Library, PubMed, ClinicalTrials.gov, Web of Science, EMBASE, China National Knowledge Infrastructure (CNKI), China Medical Information Network, and Wanfang databases. The databases were searched from inception to January 7, 2023, for cohort studies and randomized controlled trials (RCTs) comparing the use of TAF antivirals to other antivirals during pregnancy. We combined the data by means of a random-effect DerSimonian-Laird model and risk ratios (RRs) or a random-effect inverse variance model and standardized mean differences (SMDs) to determine the influence on mothers and infants. Our primary outcomes were infant weight, height, head size, birth defects, and Apgar scores. Additionally, we assessed whether newborns tested positive for hepatitis B surface antigen (HBsAg) at birth and at six months of age. The secondary outcomes of our investigation were alterationsin levels of HBV deoxyribonucleic acid (DNA), alanine aminotransferase (ALT), total bilirubin (TBIL), blood creatinine, and urine β2-microglobulin (β2-M)in mothers. An extensive literature search identified 216 relevant publications; three cohort studies and two RCTs were included in this study. A total of 341 mothers were treated with TAF, and 342 were treated with other antiviral agents. TAF was as effective as other antiviral medications at lowering HBV MTCT rates at birth and at 6months of age and ALT, TBIL, and HBV DNA levels. Moreover, compared with other antiviral drugs, TAF did not affect infant weight, height, head size, Apgar scores, and birth defects or maternal blood creatinine or β2-M levels. TAF antiviral therapy during pregnancy was found to be safe for both mothers and fetuses.

Real-world implementation of a multilevel interventions program to prevent mother-to-child transmission of HBV in China.

Reducing hepatitis B virus (HBV) mother-to-child transmission (MTCT) is a fundamental step toward the HBV elimination goal. The multicentred, multilevel SHIELD program aimed to use an intense intervention package to reduce HBV MTCT in China. This study was conducted in diverse health settings across China, encompassing 30,109 pregnant women from 178 hospitals, part of the interim analysis of stage II of the SHIELD program, and 8,642 pregnant women from 160 community-level health facilities in stage III of the SHIELD program. The study found that the overall MTCT rate was 0.23% (39 of 16,908; 95% confidence interval (CI): 0.16-0.32%) in stage II and 0.23% (12 of 5,290; 95% CI: 0.12-0.40%) in stage III. The MTCT rate was lower among participants who were compliant with the interventions (stage II: 0.16% (95% CI: 0.10-0.26%); stage III: 0.03% (95% CI: 0.00-0.19%)) than among those who were noncompliant (3.16% (95% CI: 1.94-4.85%); 1.91% (95% CI: 0.83-3.73%); P < 0.001). Our findings demonstrate that the comprehensive interventions among HBV-infected pregnant women were feasible and effective in dramatically reducing MTCT.

Eliminating mother-to-child transmission of hepatitis B virus: practice and progress in Baoan, a national pilot district of China

BackgroundWhile mother-to-child transmission (MTCT) of hepatitis B virus (HBV) remains a significant challenge in China, research investigating the effectiveness of the September 2017 pilot program to eliminate MTCT of HIV, syphilis, and HBV is limited. Baoan district, which has a higher-than-average rate of hepatitis B infection among pregnant women and strong support from the government, was one of six national pilot districts selected for the program. Therefore, this study aims to assess the progress and implementation of the elimination of MTCT of HBV in Baoan district over a period of 5 years.MethodsData was collected from the national information system for the prevention of MTCT, registration forms, and follow-up forms of pregnant women and their live births from 2018 to 2022. Joinpoint models were used to analyze changing trends over time, calculating annual percentage change (APC) and the corresponding 95% confidence interval (95%CI). Multivariate logistic regression models were used to analyze risk factors for HBV MTCT.ResultsFrom 2018 to 2022, the coverage of HBV screening during pregnancy increased from 98.29 to 99.55% (APC = 0.30, P = 0.012). The coverage of HBV early screening within 13 gestational weeks increased from 40.76 to 86.42% (APC = 18.88, P = 0.033). The prevalence of maternal HBV infection declined by an APC of − 3.50 (95% CI -6.28 ~ − 0.63). The coverage of antiviral therapy among high-risk pregnant women increased from 63.59 to 90.04% (APC = 11.90, P = 0.031). Coverage for timely administration of hepatitis B immunoglobulin, hepatitis B birth dose vaccine, and three-dose hepatitis B vaccination remained consistently above 97.50%. The coverage of post-vaccination serological testing (PVST) in high-risk infants was 56.15% (1352/2408), and the MTCT rate of HBV was 0.18%. Mothers with high-school education or below (OR = 3.76, 95% CI 1.04 ~ 13.60, P = 0.04) and hepatitis B e antigen (HBeAg) positivity (OR = 18.89, 95% CI 1.98 ~ 18.50, P = 0.01) had increased MTCT risk.ConclusionsThe implementation of comprehensive prevention strategies in Baoan district, including screening, treatment, and immunoprophylaxis, has proven effective in maintaining the MTCT of HBV at an extremely low level. However, it remains crucial to raise public awareness, specifically on the importance of improving the coverage of PVST for infants exposed to HBV.

Knowledge and Willingness to Utilize Hepatitis B Preventive Measures among Pregnant Women in Ado-Ekiti, Southwest, Nigeria.

Mother-to-child transmission remains an important mode of transmission of hepatitis B infection particularly in endemic areas. The knowledge and practices of pregnant women about mother-to-child transmission (MTCT) of hepatitis B virus (HBV) may influence the uptake of strategies to reduce mother-to-child transmission of infection. This study assessed the knowledge and willingness to uptake hepatitis B virus infection preventive services among pregnant women in Ado-Ekiti, Nigeria. This was a cross-sectional study that involved 373 pregnant women at the Ekiti State University Teaching Hospital (EKSUTH) and Maternal Child Specialist Clinics, Ado-Ekiti, Nigeria. A structured questionnaire was used to assess their knowledge, practices, and perceptions about MTCT of hepatitis B infection. Only 52.5% (196) of the respondents had good knowledge, although the majority 290 (77.7%) had heard of hepatitis B infection prior to the survey. Only 147 (39.4%) of the respondents had ever had hepatitis B screening. More persons with professional jobs had good knowledge about hepatitis B infection compared with other occupations (p < 0.001). However, more respondents aged 30-34 years had poor knowledge about hepatitis B infection compared with other age groups (p = 0.045). Respondents with good knowledge about hepatitis B infection were willing to uptake hepatitis B infection prevention services (p < 0.001). This study showed that respondents with professional jobs had good knowledge about hepatitis B infection and those who had good knowledge about the infection were willing to utilize hepatitis B preventive measures. Awareness of MTCT of HBV did not translate into good practice as only few respondents had screened for hepatitis B. There is a need to intensify education about modes of transmission of hepatitis B infection with an emphasis on promoting good preventive practices.

Weak Adoption and Performance of Hepatitis B Birth-Dose Vaccination Programs in Africa: Time to Consider Systems Complexity?-A Scoping Review.

The persistent burden of chronic hepatitis B among ≤5-year-old children in Africa suggests missed opportunities for controlling mother-to-child transmission (MTCT) of the hepatitis B virus (HBV). This scoping review maps the evidence base on the risk of HBV MTCT, the status of HBV MTCT mitigation strategies including hepatitis B birth-dose vaccination, and the role of systems complexity on the suboptimal adoption and performance of hepatitis B birth-dose vaccination programs in Africa. Overall, 88 peer-reviewed and grey literature sources published between 2000-2022 were included in this review. The growing evidence base consistently argues for a heightened risk of HBV MTCT amidst the HIV co-epidemic in the region. Without universal HBV screening programs integrated within broader antenatal care services, current selective hepatitis B birth-dose vaccination is unlikely to effectively interrupt HBV MTCT. We underscore critical health systems-related barriers to universal adoption and optimal performance of hepatitis B birth-dose vaccination programs in the region. To better conceptualize the role of complexity and system-wide effects on the observed performance of the program, we propose an adapted systems-based logic model. Ultimately, exploring contextualized complex systems approaches to scaling-up universal hepatitis B birth-dose vaccination programs should form an integral part of the regional research agenda.

Impact of timing on protection of combined immunoprophylaxis in preventing mother-to-child transmission of hepatitis B virus: a retrospective study

Objective: To evaluate the impact of timing combined immunoprophylaxis on mother-to-child transmission (MTCT) of the hepatitis B virus (HBV) in pregnant women living with hepatitis B. Methods: A retrospective cohort study was included HBsAg-positive pregnant women who delivered full-term at Tianjin Third Central Hospital from January 2019 to December 2021. The objective of this study is to determine whether early administration of hepatitis B immune globulin (HBIG) and the first dose of hepatitis B vaccination after birth can further improve protection. Result: A total of 694 pregnant women living with hepatitis B were included; 93 infants from these mothers were lost to follow-up [including moving (n = 21), emigrating (n = 26), changing contact information (n = 27), and other reasons (n = 19)], leaving 601 infants for analysis. The incidence in babies born to mothers with hepatitis B was 1.50% (9/601). Based on the different timing of combined immunoprophylaxis administration after birth, 601 infants were divided into two groups (within 2 h and within 2–12 h). The incidence in babies born to mothers with hepatitis B were 0.32% (1/308) and 2.73% (8/293) for infants who received combined immunoprophylaxis within 2 h and between 2 and 12 h of birth, respectively (p = 0.037). The infection incidence of infants born to HBeAg-positive mothers and HBeAg-positive mothers who did not receive antiviral treatment during pregnancy was lower in the 2-h group compared to the 2–12 h group (0.72% vs. 5.84%, p = 0.04 and 1.20% vs. 9.46%, p = 0.047). Conclusion: Using combined immunoprophylaxis as soon as possible (within two hours of birth) may protect against MTCT of HBV more.

Risk of mother-to-child transmission after amniocentesis in pregnant women with hepatitis B virus: a retrospective cohort study

Amniocentesis is the most widely used invasive prenatal diagnostic sampling technique. However, whether this increases the risk of mother-to-child transmission of infectious diseases remains controversial. This study aimed to determine whether amniocentesis increases the risk of hepatitis B virus infection in infants who received standard prophylaxis, and to assess the related risk factors for mother-to-child transmission in women who underwent amniocentesis during pregnancy. This retrospective analysis used the clinical data of pregnant women with hepatitis B virus infection at West China Second University Hospital, Sichuan University in 2019. After meeting the inclusion criteria, the participants were divided into 2 groups on the basis of whether they had undergone amniocentesis during pregnancy. The infant hepatitis B virus serologic status was followed 1 to 6 months after completion of immunization. The infant testing positive for hepatitis B surface antigen and negative for Hepatitis B surface antibody indicated mother-to-child transmission of hepatitis B virus. In total, 1764 pregnant women with hepatitis B virus infection were enrolled. Of these, 846 underwent amniocentesis during pregnancy and 918 did not. All offspring received a standardized immunoprophylaxis schedule. The overall mother-to-child transmission rate for hepatitis B virus was 0.6% (5/846) in the amniocentesis group and 0.4% (4/918) in the control group (P=.745). Subgroup analysis showed that the mother-to-child transmission rate in hepatitis B e antigen-positive women was 1.8% (2/111) in the amniocentesis group and 1.0% (2/209) in the control group (P=.612). In women with high viral load, the mother-to-child transmission rate was 1.3% (1/78) vs 0.9% (1/107) (amniocentesis group vs control group; P=1.000). In the amniocentesis group, 31 amniotic fluid specimens had an abnormal appearance (bloody or brown). Univariate analysis showed that the mother-to-child transmission rates of these mothers were statistically higher than those of mothers with pale yellow or transparent amniotic fluid (2/31 vs 3/815; relative risk, 17.527 [3.037-101.151]; P=.012). Amniocentesis did not increase the risk of mother-to-child transmission of hepatitis B virus in infants who received a standardized immunoprophylaxis schedule, including those with mothers who were hepatitis B e antigen-positive or had a high viral load. However, the abnormal appearance (bloody or brown) of the amniotic fluid obtained during amniocentesis may indicate increased risk of mother-to-child transmission for hepatitis B virus.

Hepatitis B Virus Prevalence and Mother-to-Child Transmission Risk in an HIV Early Intervention Cohort in KwaZulu-Natal, South Africa.

HIV and hepatitis B virus (HBV) prevalence are both high in KwaZulu-Natal, South Africa. HIV coinfection negatively affects HBV prognosis and can increase the likelihood of HBV mother-to-child transmission (MTCT). In an early HIV infant treatment intervention cohort of HIV-transmitting mother-child pairs in KwaZulu-Natal, we characterized maternal HBV prevalence and screened infants at risk. Infants were treated for HIV MTCT at birth, and combination regimens incidentally active against HBV were initiated within 21 days. Maternal samples (N = 175) were screened at birth for HBV infection (HBV surface antigen [HBsAg]), exposure to HBV (HBV anti-core IgG), and vaccination responses (HBV anti-S positive without other HBV markers). Infants of mothers who were HBV positive were screened for HBsAg at 1 and 12 months. Evidence of HBV infection was present in 8.6% (n = 15) of maternal samples. Biomarkers for HBV exposure were present in 31.4% (n = 55). Evidence of HBV vaccination was uncommon in mothers (8.0%; n = 14). Despite prescription of antiretroviral therapy (ART) active against HBV, HBV DNA was detectable in 46.7% (7/15) of mothers who were HBsAg positive. Three mothers had HBV viral loads >5.3 log10 IU/mL, making them high risk for HBV MTCT. Screening of available infant samples at 1 month (n = 14) revealed no cases of HBV MTCT. At 12 months, we identified 1 HBV infection (1/13), and serologic evidence of vaccination was present in 53.8% (7/13) of infants. This vulnerable cohort of HIV-transmitting mothers had a high prevalence of undiagnosed HBV. Early infant ART may have reduced the risk of MTCT in high-risk cases. Current HBV guidelines recommend ART prophylaxis, but these data underline the pressing need to increase availability of birth dose vaccines.

The risk of mother-to-child transmission of hepatitis B virus infection in Ethiopia: A systematic review and meta-analysis.

Mother-to-child transmission (MTCT) of hepatitis B virus (HBV) is a predominant route of infection for children in Ethiopia. No study has so far reported a nationwide estimate of the risk of MTCT of HBV. We conducted a meta-analysis of surveys and estimated the pooled risk of MTCT of HBV in the context of human immunodeficiency virus (HIV) infection. We searched PubMed, EMBASE, Web of Science, Africa Index Medicus, and Google Scholar databases for peer-reviewed articles. The pooled risk of MTCT of HBV was estimated using the DerSimonian-Laird technique with logit transformed proportions and statistical heterogeneity was estimated using I2 statistic, which was explored by subgroup and meta-regression analyses. The overall pooled risk of MTCT of HBV in Ethiopia was 25.5% (95% CI, 13.4%-42.9%). In women without HIV infection, the risk of MTCT of HBV was 20.7% (95% CI 2.8%-70.4%), and 32.2% (95% CI 28.1%-36.7%) in women with HIV infection. After excluding the outlier study, the risk of MTCT of HBV in studies that included only HIV negative women was 9.4% (95% CI, 5.1%-16.6%). The risk of MTCT of HBV in Ethiopia widely varied by HBV/HIV coinfection. A sustainable control and elimination of HBV in Ethiopia requires improved access to birth-dose HBV vaccine and implement immunoglobulin prophylaxis for exposed infants. Given the limited health resources in Ethiopia, prenatal antiviral prophylaxis integrated with antenatal care may be a cost-effective approach to significantly reduce the risk of MTCT of HBV.

Association of vitamin D and polymorphisms of its receptor with antiviral therapy in pregnant women with hepatitis B.

The interruption of mother-to-child transmission (MTCT) is considered important to decrease the individual and population morbidity of hepatitis B virus (HBV) infection as well as the global burden of hepatitis B. Serum vitamin D (VD) is associated with hepatitis B. To assess whether baseline VD levels and single nucleotide polymorphisms of the VD receptor gene (VDR SNPs) are associated with the efficacy of tenofovir disoproxil fumarate (TDF) in the prevention of MTCT in pregnant women with high HBV viral loads. Thirty-eight pregnant women who were at high risk for MTCT of HBV (those with an HBV DNA level ≥ 2 × 105 IU/mL during 12-24 wk of gestation) receiving antiviral therapy of TDF between June 1, 2019 and June 30, 2021 in Mianyang were included in this retrospective study. The women received 300 mg TDF once daily from gestational weeks 24-28 until 3 mo after delivery. To further characterize the clinical relevance of maternal serum HBV DNA levels, we stratified patients according to HBV DNA level as follows: Those with levels < 2 × 105 (full responder group) vs those levels ≥ 2 × 105 IU/mL (partial responder group) at delivery. Serum levels of 25-hydroxyvitamin D [25(OH)D], liver function markers, virological parameters, VDR SNPs and other clinical parameters were collected to analyze their association with the efficacy of TDF. The Mann-Whitney U test or t test was used to analyze the serum levels of 25(OH)D in different groups. Multiple linear regressions were utilized to analyze the determinants of the maternal HBV DNA level at delivery. Univariate and multivariate logistic regression analyses were employed to explore the association of targeted antiviral effects with various characteristics at baseline and delivery. A total of 38 pregnant women in Mianyang City at high risk for MTCT of HBV were enrolled in the study. The MTCT rate was 0%. No mother achieved hepatitis B e antigen or hepatitis B surface antigen (HBsAg) clearance at delivery. Twenty-three (60.5%) participants were full responders, and 15 (39.5%) participants were partial responders according to antiviral efficacy. The present study showed that a high percentage (76.3%) of pregnant women with high HBV viral loads had deficient (< 20 ng/mL) or insufficient (≥ 20 but < 31 ng/mL) VD levels. Serum 25(OH)D levels in partial responders appeared to be significantly lower than those in full responders both at baseline (25.44 ± 9.42 vs 17.66 ± 5.34 ng/mL, P = 0.006) and delivery (26.76 ± 8.59 vs 21.24 ± 6.88 ng/mL, P = 0.044). Serum 25(OH)D levels were negatively correlated with maternal HBV DNA levels [log(10) IU/mL] at delivery after TDF therapy (r = -0.345, P = 0.034). In a multiple linear regression analysis, maternal HBV DNA levels were associated with baseline maternal serum 25(OH)D levels (P < 0.0001, β = -0.446), BMI (P = 0.03, β = -0.245), baseline maternal log10 HBsAg levels (P = 0.05, β = 0.285) and cholesterol levels at delivery (P = 0.015, β = 0.341). Multivariate logistic regression analysis showed that baseline serum 25(OH)D levels (OR = 1.23, 95%CI: 1.04-1.44), maternal VDR Cdx2 TT (OR = 0.09, 95%CI: 0.01-0.88) and cholesterol levels at delivery (OR = 0.39, 95%CI: 0.17-0.87) were associated with targeted antiviral effects (maternal HBV DNA levels < 2 × 105 at delivery). Maternal VD levels and VDR SNPs may be associated with the efficacy of antiviral therapy in pregnant women with high HBV viral loads. Future studies to evaluate the therapeutic value of VD and its analogs in reducing the MTCT of HBV may be justified.

C2729T mutation associated with HBV mother-to-child transmission reduces HBV production via suppressing LHBs expression

ABSTRACT Mother-to-child transmission (MTCT) is still the main route of hepatitis B virus (HBV) infection. However, the virological factors affecting HBV MTCT have not been fully elucidated. In this study, based on a prospective cohort of mother-infant pairs with positive maternal hepatitis B surface antigen (HBsAg), we found that the average nucleotide mutation rate of HBV preS1 promoter (SPI) region in the immunoprophylaxis success group was significantly higher than that in the immunoprophylaxis failure group. Among the nucleotide mutations of the HBV SPI region, the C2729T mutation had the highest frequency. Next, we found that the C2729T mutation promoted HBsAg release but reduced HBV production by suppressing the expression of large hepatitis B surface antigen (LHBs), and overexpressing LHBs could rescue this phenomenon. Based on the fact that the C2729T mutation could alter the binding site of hepatocyte nuclear factor 1 (HNF1) in the HBV SPI region, we uncovered that such an alteration could downregulate the transcriptional activity of SPI by attenuating the binding ability of HNF1 and HBV SPI region. This study suggests that HBV C2729T mutation may contribute to the immunoprophylaxis success of HBV MTCT by reducing HBV production, which supplements the virological factors affecting HBV MTCT.

Strategies to Prevent Mother-to-child Transmission of Hepatitis B Virus.

Mother-to-child transmission (MTCT) of hepatitis B virus (HBV) is the primary cause of chronic HBV infection worldwide. MTCT prevention and antiviral treatment of infected individuals could eliminate this public health burden. Antiviral treatment of hepatitis B surface antigen (HBsAg)-positive pregnant women and immunoprophylaxis with HBV vaccine and hepatitis B immune globulin are the most effective strategies to interfere with MTCT of HBV. However, for worldwide application of those strategies, feasibility, availability, cost, safety, and effectiveness should be considered. Cesarean section and breastfeeding avoidance in hepatitis B e antigen-positive mothers with a high viral load and without antiviral therapy during pregnancy could be an option, but more supporting evidence is needed. HBsAg screening of all pregnant women is recommended when initiating antiviral therapy and immunoprophylaxis for MTCT prevention, except in areas with limited resources. Timely HBV vaccination series administered soon after birth might be the mainstay of prevention. This review aimed to provide a concise update on the effectiveness of available strategies to prevent MTCT of HBV.

Effects of hepatitis B virus infection and strategies for preventing mother-to-child transmission on maternal and fetal T-cell immunity.

One of the most common routes of chronic hepatitis B virus (HBV) infection is mother-to-child transmission (MTCT). Approximately 6.4 million children under the age of five have chronic HBV infections worldwide. HBV DNA high level, HBeAg positivity, placental barrier failure, and immaturity of the fetal immune are the possible causes of chronic HBV infection. The passive-active immune program for children, which consists of the hepatitis B vaccine and hepatitis B immunoglobulin, and antiviral therapy for pregnant women who have a high HBV DNA load (greater than 2 × 105 IU/ml), are currently two of the most important ways to prevent the transmission of HBV from mother to child. Unfortunately, some infants still have chronic HBV infections. Some studies have also found that some supplementation during pregnancy can increase cytokine levels and then affect the level of HBsAb in infants. For example, IL-4 can mediate the beneficial effect on infants' HBsAb levels when maternal folic acid supplementation. In addition, new research has indicated that HBV infection in the mother may also be linked to unfavorable outcomes such as gestational diabetes mellitus, intrahepatic cholestasis of pregnancy, and premature rupture of membranes. The changes in the immune environment during pregnancy and the hepatotropic nature of HBV may be the main reasons for the adverse maternal outcomes. It is interesting to note that after delivery, the women who had a chronic HBV infection may spontaneously achieve HBeAg seroconversion and HBsAg seroclearance. The maternal and fetal T-cell immunity in HBV infection is important because adaptive immune responses, especially virus-specific CD8 T-cell responses, are largely responsible for viral clearance and disease pathogenesis during HBV infection. Meanwhile, HBV humoral and T-cell responses are important for the durability of protection after fetal vaccination. This article reviews the literature on immunological characteristics of chronic HBV-infected patients during pregnancy and postpartum, blocking mother-to-child transmissions and related immune mechanisms, hoping to provide new insights for the prevention of HBV MTCT and antiviral intervention during pregnancy and postpartum.

Coinfection Dynamics of HBV-HIV/AIDS with Mother-to-Child Transmission and Medical Interventions

In this study, we analyzed the effect of mother-to-child transmission (MTCT) of hepatitis B virus (HBV) and human immunodeficiency virus (HIV) on the transmission dynamics of their coinfection to make a recommendation based on reasons to public health sector, policy makers, and programme implementers. We proved that the solutions of the sub and full models are positive and bounded. The effective reproduction numbers of the models are derived using the next generation matrix method. The disease-free and endemic equilibria of the submodels and the coinfection model are computed, and the stability of those equilibria is analyzed using Routh-Hurwitz criteria after computing the associated effective reproduction numbers. We performed a sensitivity analysis to show the influence of different parameters on the effective reproduction number of HBV-HIV/AIDS coinfection model, and we identified the most sensitive parameters are τ 2 and α 1 , which are the rate of MTCT of HIV and treatment rate for HBV infected class, respectively. The numerical simulation of the model is done using MATLAB and the findings from the simulations are discussed. From the results of numerical simulations, we observed that an increase in the rates of MTCT of HBV and HIV exacerbated HBV-HIV/AIDS coinfection, while a decrease in the rates of MTCT of these infections would decline the number of cases, minimize the spread, and help to eliminate HBV-HIV/AIDS coinfection from the society gradually.

Prospective cohort study of prevention of mother to child transmission of hepatitis B infection and 9 months follow-up of hepatitis B-exposed infants at Ile-Ife, Nigeria

ObjectivesEliminating mother-to-child transmission (MTCT) of hepatitis B virus (HBV) is central to WHO’s target of reducing hepatitis B infection in children to <0.1% by 2030. While Nigeria accounts for 8.3%...

Incidence of mother-to-child transmission of hepatitis B in relation to maternal peripartum antiviral prophylaxis: Asystematic review and meta-analysis.

Mother-to-child transmission (MTCT) of the hepatitis B virus (HBV) is a serious public health challenge. Estimating HBV MTCT incidence by region under different prophylaxis regimens is critical to understanding the regional disease burden and prioritizing interventions. This study aimed to calculate HBV MTCT incidence under different prophylaxis regimens globally and regionally and identify the HBV DNA threshold for maternal peripartum antiviral prophylaxis. This review was registered in advance in PROSPERO (CRD 42019120567). We searched PubMed, Embase, China National Knowledge Infrastructure, ClinicalTrials.gov, and Cochrane Library databases for studies on MTCT in pregnant women with chronic HBV infection from their inception until June 13, 2022. MTCT was defined as hepatitis B surface antigen (HBsAg) or HBV DNA seropositivity in infants aged 6-12 months. We calculated the pooled HBV MTCT incidence using the DerSimonian-Laird random-effects model. Among 300 studies, 3402 of 63 293 infants had HBV due to MTCT. Without prophylaxis regimens, the pooled HBV MTCT incidence was 31.3%, ranging from 0.0% (95% confidence interval [CI] 0.0%-6.0%; European Region) to 46.1% (95% CI 29.7%-63.0%; Western Pacific Region). Following the introduction of the hepatitis B vaccine, the HBV MTCT incidence decreased from 82.9% to 15.9% in HBeAg-positive women and from 10.3% to 2.3% in HBeAg-negative women. Maternal peripartum antiviral treatment alongside infant immunoprophylaxis further decreased MTCT incidence to 0.3% (95% CI 0.1%-0.5%). Despite infant immunoprophylaxis, the incidences of MTCT at maternal HBV DNA levels of <2.30, 2.00-3.29, 3.00-4.29, 4.00-5.29, 5.00-6.29, 6.00-7.29 and ≥7.00 log10 IU/ml were 0.0% (95% CI 0.0%-0.0%), 0.0% (95% CI 0.0%-0.0%), 0.0% (95% CI 0.0%-0.5%), 0.6% (95% CI 0.0%-2.6%), 1.0% (95% CI 0.0%-3.1%), 4.3% (95% CI 1.8%-7.5%), and 9.6% (95% CI 7.0%-12.5%), respectively. HBV MTCT incidence varies across regions. The Western Pacific Region bears the heaviest burden. Peripartum antiviral prophylaxis plus infant immunoprophylaxis is promising for interrupting HBV MTCT. Regarding the HBV DNA threshold for peripartum antiviral prophylaxis, maternal HBV DNA of 4.00 log10 IU/ml or greater seems justified.

HBx 128-133 Deletion Affecting HBV Mother-to-Child Transmission Weakens HBV Replication via Reducing HBx Level and CP/ENII Transcriptional Activity.

Some infants born to hepatitis B surface antigen (HBsAg)-positive mothers, especially born to hepatitis B e antigen (HBeAg)-positive mothers, can still be infected with hepatitis B virus (HBV) through mother-to-child transmission (MTCT) of HBV and develop chronic HBV infection. At present, the virological factors affecting HBV MTCT are still unclear. In this study, we found that the mutation rates of amino acids in the HBV X region were high, and there were obvious differences between the immunoprophylaxis success group and the immunoprophylaxis failure group of HBeAg-positive mothers. Specifically, the mutation rate of HBx 128–133 deletion (x128–133del) or corresponding nucleotide 1755–1772 deletion (nt1755–1772del) in the immunoprophylaxis success group was significantly higher than that in the immunoprophylaxis failure group. Furthermore, we found that x128–133del could weaken HBV replication by reducing the level of the HBx protein due to the increased proteasome-dependent degradation of HBx protein, and the transcriptional activity of HBV core promoter (CP)/enhancer II (ENII) due to the attenuated binding capacity of hepatocyte nuclear factor 4α (HNF4α) to HBV CP/ENII. This study suggests that x128–133del may contribute to immunoprophylaxis success, which may be helpful in clarifying the virological mechanism affecting HBV MTCT and formulating an optimal immunization strategy for children born to HBeAg-positive mothers.

Impaired CD8+ T cells in term pregnancy decidua with chronic hepatitis B virus infection.

Hepatitis B virus (HBV) infection is more likely to develop a state of chronicity in early life, particularly mother-to-child transmission (MTCT) of HBV in the fetus during pregnancy. Till now, little is known about the impact of chronic HBV infection on the immune status of the maternal-fetus interface, and the immune profile of placental lymphocytes in MTCT of HBV is poorly understood. Thirteen term pregnant women with chronic HBV infection (HBV-PW) and thirteen normal pregnant women as healthy control (HC-PW) were enrolled. The profile of placental immune cells and paired peripheral blood were analyzed by flow cytometry and immunohistochemistry. Compared with HC-PW, the frequency of CD8+ T cells from the term placenta of HBV-PW was significantly reduced. These cells showed decreased expression of activation molecules CD69 and HLA-DR; thus, decidual CD8+ T cells from HBV-PW demonstrated hypofunctional signature as evidenced by significantly reduced production of IFN-γ, as well as compromised ability of degranulation and proliferation. These findings supported that hypoactivated decidual CD8+ T cells might possess compromised ability in chronically HBV-infected term pregnant women. Our study provides robust evidence for the necessity and importance of antiviral intervention in HBV-PW to prevent MTCT of HBV.

Progress Toward the Elimination of Mother-to-Child Transmission of Hepatitis B Virus - Worldwide, 2016-2021.

Mother-to-child transmission (MTCT) of hepatitis B virus (HBV) often results in chronic HBV infection, the leading cause of cirrhosis and liver cancer (1). If not vaccinated, nine in 10 children infected at birth will become chronically infected. Globally, an estimated 6.4 million (range=4.4-10.8 million) children aged ≤5 years are living with chronic HBV infection (2). In 2016, the World Health Assembly endorsed the goal to eliminate viral hepatitis as a public health threat by 2030, including the elimination of MTCT of HBV (3). Elimination of MTCT of HBV can be validated by demonstrating ≤0.1% prevalence of HBV surface antigen (HBsAg) among children aged ≤5 years, as well as ≥90% coverage with hepatitis B birth dose (HepB-BD) and 3 doses of hepatitis B vaccine (HepB3) (4,5). This report describes global progress toward elimination of MTCT of HBV during 2016-2021. By December 2020, 190 (98%) of 194 World Health Organization (WHO) member states* had introduced universal infant vaccination with hepatitis B vaccine (HepB), and 110 (57%) countries provided HepB-BD to all newborns. During 2016-2020, global HepB3 coverage remained between 82% and 85%, whereas HepB-BD coverage increased from 37% to 43%. In 2020, among the 99 countries reporting both HepB3 and HepB-BD coverage, 41 (41%) achieved ≥90% coverage with both. By December 2021, serosurveys documented ≤0.1% HBsAg prevalence among children in 11 countries. Accelerating HepB-BD introduction, increasing HepB3 coverage, and monitoring programmatic and impact indicators are essential for elimination of MTCT of HBV.