Exploring the impact of hepatitis B immunoglobulin and antiviral interventions to reduce vertical transmission of hepatitis B virus

Hepatitis B virus(HBV)infection is a major public health burden.In HBV endemic regions,high prevalence is also correlated with the infections acquired in infancy through perinatal transmission or early childhood exposure to HBV,the socalled mother-to-child transmission(MTCT).Children who are infected with HBV at a young age are at higher risk of developing chronic HBV infection than those infected as adults,which may lead to worse clinical outcome.To reduce the incidence of HBV MTCT,several interventions for the infants or the mothers,or both,are already carried out.This review explores the newest information and approaches available in literature regarding HBV MTCT prevalence and its challenges,especially in high HBV endemic countries.This covers HBV screening in pregnant women,prenatal intervention,infant immunoprophylaxis,and postvaccination serological testing for children.

Parents’s knowledge and awareness about hepatitis B can influence the vaccination of their children

BACKGROUND Birth-dose(Hep-BD)followed by three additional doses(Hep-B3)of hepatitis B virus(HBV)vaccine are key to eliminating HBV by 2030.Unfortunately,Hep-BD and Hep-B3 coverage in our country is poor.AIM To studied the parent’s knowledge and awareness about HBV infection,its prevention,consequences and vaccination.METHODS Parents of 6 months to 8 years old children were interviewed to assess their knowledge&awareness about hepatitis B,its transmission,prevention,illness caused by this,and vaccination.Eighteen close-ended questions were admini-stered,and responses were recorded as‘yes’,‘no’,or‘not sure’.HBV knowledge score was calculated based on the sum of correct answers.Each correct response scored one point and incorrect,missing or‘not sure’responses received no points.Categorical data are presented as number(%)and numerical data are expressed as median.Data were compared using Chi2 tests and level of significance was kept as P<0.05.RESULTS Parents(58.3%mothers)of 384 children(89.9%age<5 years;82%age-appropriately vaccinated)were included.Three hundred and twenty-two(83.9%)children were Hep-B3 vaccinated.94.3%,87.5%,and 29.2%parents knew about polio,tetanus,and hepatitis B vaccine.Overall,41.2%,15.8%,and 23%parents knew about hepatitis B transmission,consequences of infection,and prevention respectively.Only 7.6%parents knew about three-dose schedule of hepatitis B vaccination.Only 23%parents believed that vaccine could prevent HBV,15.7%knew that HBV affects liver.Parents of Hep-B3 vaccinated children were significantly more aware about HBV than the parents of unvaccinated children(P<0.05 for 17/18 questions).CONCLUSION The knowledge and awareness among the parents about hepatitis B is poor.The Increasing knowledge/awareness about HBV among parents may improve Hep-B3 vaccination coverage.

Efficacy and safety of tenofovir disoproxil fumarate in pregnancy for the prevention of vertical transmission of HBV infection

AIM:To evaluate the effects of tenofovir disoproxil fumarate(TDF)use during late pregnancy to reduce hepatitis B virus(HBV)transmission in highly viremic mothers.METHODS:This retrospective study included 45 pregnant patients with hepatitis B e antigen(+)chronic hepatitis B and HBV DNA levels>107copies/mL who received TDF 300 mg/d from week 18 to 27 of gestation(n=21).Untreated pregnant patients served as controls(n =24).All infants received 200 IU of hepatitis B immune globulin(HBIG)within 24 h postpartum and 20μg of recombinant HBV vaccine at 4,8,and 24 wk.Perinatal transmission rate was determined by hepatitis B surface antigen and HBV DNA results in infants at week 28.RESULTS:At week 28,none of the infants of TDFtreated mothers had immunoprophylaxis failure,whereas2(8.3%)of the infants of control mothers had immunoprophylaxis failure(P=0.022).There were no differences between the groups in terms of adverse events in mothers or congenital deformities,gestational age,height,or weight in infants.At postpartum week 28,significantly more TDF-treated mothers had levels of HBV DNA<250 copies/mL and normalized alanine aminotransferase compared with controls(62%vs none,P<0.001;82%vs 61%,P=0.012,respectively).CONCLUSION:TDF therapy during the second or third trimester reduced perinatal transmission rates of HBV and no adverse events were observed in mothers or infants.

Prevention of vertical transmission of hepatitis B virus infection

Hepatitis B virus(HBV)is the leading cause of chronic viral hepatitis.Annually,almost two million children younger than 5 years acquire the infection,mostly through vertical or horizontal transmission in early life.Vertical transmission of HBV is a high efficacy phenomenon ranging,in the absence of any preventive interventions,from 70%to 90%for hepatitis e antigen positive mothers and from 10%to 40%for hepatitis e antigen-negative mothers.Maternal viraemia is a preeminent risk factor for vertical transmission of HBV.Maternal screening is the first step to prevent vertical transmission of HBV.Hepatitis B passive and active immunoprophylaxis at birth together with antiviral treatment of highly viraemic mothers are the key strategies for global elimination of HBV infection.Strategies are needed to promote implementation of birth-dose vaccination and hepatitis B immunoglobulins in low-and middle-income countries where the prevalence of the infection is at the highest.

Applicability and efficacy of a model for prevention of perinatal transmission of hepatitis B virus infection:Single center study in Egypt

AIM: To identify possible maternal risk factors for hepatitis B virus (HBV) acquisition and assess the efficacy of immunoprophylaxis given to infants born to hepatitis B virus surface antigen (HBsAg) positive mothers.

Missed Prevention of Mother-to-Child Transmission of HIV (PMTCT) Visits and Associated Programmatic Predictors: A Pilot Study

Missed Prevention of Mother-to-Child Transmission of HIV (PMTCT) visits have contributed to the delayed achievement of elimination of mother-to-child transmission of HIV. Missed visits promote attrition from prevention of mother-to-child transmission of HIV program and antiretroviral drug resistance. The purpose of the study was to determine the prevalence of missed PMTCT visits and its associated predictors. A descriptive cross sectional survey was carried out at a District Hospital in Goromonzi, Zimbabwe. Fifty-three women completed closed-ended questionnaires pertaining to PMTCT visits and exposure to PMTCT activities. A total of 24.5% missed at least one scheduled PMTCT visit. Statistically significant predictors of not missing a PMTCT visit were satisfaction with family support (β = &minus;0.73, p = 0.029) and level of satisfaction with PMTCT services (β = &minus;0.00076;p = 0.04). The number of days by which scheduled visits were missed were inversely correlated with visit number (β = &minus;2.99, p = 0.04). Enhanced family support and quality improvement to improve patient satisfaction may reduce missed visits. Availing women with a more active role in PMTCT may also reduce the prevalence of missed visits.

Virologic characteristics of hepatitis B virus in patients infected via maternal-fetal transmission

AIM: To determine whether HBV with the same characteristics causes dissimilar mutations in different hosts. METHODS: Full-length HBV genome was amplified and linked with pMD T18 vector. Positive clones were selected by double-restriction endonuclease digestion (EcoRⅠ and HindⅢ) and PCR. Twenty seven clones were randomly selected from an asymptomatic mother [at two time points: 602 (1 d) and 6022 (6 mo)] and her son [602 (S)], and the phylogenetic and mutational analysis was performed using BioEditor, Clustal X and MEGA software. Potential immune epitopes were determined by the Stabilized Matrix Method (SMM), SMM-Align Method and Emini Surface Accessibility Prediction. RESULTS: All of the 27 sequences were genotype C, the divergence between the mother and son was 0%-0.8%. Compared with another 50 complete sequences of genotype C, the mother and her son each had 13 specific nucleotides that differed from the other genotype C isolates. AA 1-11 deletion in preS1 was the dominant mutation in the mother (14/18). The 1762T/1764A double mutation existed in all clones of the mother, 3 of them were also coupled with G1896A mutation, but none were found in the son.17 bp deletion starting at nucleotide 2330 was the major mutation (5/9) in the son, which caused seven potential HLA class Ⅰ epitopes and one B cell epitope deletion, and produced a presumptive new start codon, downstream from the original one of the P gene. CONCLUSION: The HBV strain in the son came from his mother, and discrepant mutation occurred in the mother and her son during infection.

Studies on the integration of hepatitis B virus DNA sequence in human sperm chromosomes

Aim: To study the integration of hepatitis B virus (HBV) DNA into sperm chromosomes in hepatitis B patients and the features of its integration. Methods: Sperm chromosomes of 14 subjects (5 healthy controls and 9 HB patients, including 1 acute hepatitis B, 2 chronic active hepatitis B, 4 chronic persistent hepatitis B, 2 HBsAg chronic carriers with no clinical symptoms) were prepared using interspecific in vitro fertilization between zona-free hamster oocytes and human spermatozoa. Fluorescence in situ hybridization (FISH) to sperm chromosome spreads was carried out with biotin-labeled full length HBV DNA probe to detect the specific HBV DNA sequences in the sperm chromosomes. Results: Specific fluorescent signal spots for HBV DNA were seen in sperm chromosomes of one patient with chronic persistent hepatitis B. In 9(9/42) sperm chromosome complements containing fluorescent signal spots, one presented 5 obvious FISH spots and the others 2 to 4 signals. The fluorescence intensity showed significant difference among the signal spots. The distribution of signal sites among chromosomes seems to be random. Conclusion: HBV could integrate into human sperm chromosomes. Results suggest that the possibility of vertical transmission of HBV via the germ line to the next generation is present.

Mutation analyses of integrated HBV genome in hepatitis B patients

Little has been learnt in the last 30 years about detection of HBV genome as well as its mutation analysis between hepatitis B fathers （HBF） and their children. In this study, we used nest polymerase chain reaction （PCR）, fluorescence in situ hybridization （FISH）, and DNA sequencing analysis, to examine the integrated HBV genome in paraffin-embedded testis tissues, which were taken as samples from HBE and in peripheral blood mononuclear cells （PBMC） from 74 cases of HBFs and their children who were born after their fathers＇ HBV infection （caHBF）. We found that HBV DNA existed in testis tissues, mainly in the basilar parts of the seminiferous tubules, and also in PBMC of HBE It was also documented that there were point mutations of poly-loci, insertions and deletions of nucleotides in integrated HBV genomes, and the types of gene mutations in the HBFs were similar to those in caHBE This study addresses the major types of gene mutations in integrated HBV genome in human patients and also presents reliable evidence of possible genetic transmission of hepatitis B.

Comprehensive review of telbivudine in pregnant women with chronic hepatitis B

AIM:To achieve an evidence-based conclusion regarding the safety and efficacy of telbivudine during pregnancy.METHODS:A pooled analysis of data from a literature search reported 1739 pregnancy outcomes(1673 live births)from 1725 non-overlapping pregnant women treated with telbivudine.The prevalence of live birth defects(3.6/1000)was similar to that of the nonantiviral controls(3.0/1000)and not increased as compared with overall prevalence(14.5 to 60/1000).No target organ toxicity was identified.The prevalence of spontaneous abortion in pregnant women treated with telbivudine(4.2/1000)was not increased compared with the overall prevalence(16/1000).The mother-to-child transmission rate was significantly reduced in pregnant women treated with telbivudine(0.70%)compared to those treated with the non-antiviral controls(11.9%;P<0.0001)or compared to the historical rates of hepatitis B virus(HBV)-infected population without antiviral treatment(10%-15%).RESULTS:Cumulatively 489 pregnancy cases have been reported in the telbivudine pharmacovigilance database(with a cut-off date 31 August 2014),of those,308 had known pregnancy outcomes with 249 cases of live births(239 cases of live birth without congenital anomaly and 10 cases of live birth with congenital anomaly).In the latest antiretroviral pregnancy registry report(1 January 1989 through 31 January 2015)of27 patients exposed to telbivudine during pregnancy(18,6 and 3 during first,second and third trimester,respectively)19 live births were reported and there were no cases of birth defects reported.CONCLUSION:Telbivudine treatment during pregnancy presents a favorable safety profile without increased rates of live birth defects,spontaneous abortion or elective termination,or fetal/neonatal toxicity.Exposure to telbivudine in the first,second and third trimester of pregnancy has been shown to significantly reduce the risk of HBV transmission from mother to child on the basis of standard immune prophylaxis procedure.

Management of chronic hepatitis B in pregnancy

Pregnancy associated with chronic hepatitis B (CHB) is a common and important problem with unique challenges. Pregnant women infected with CHB are different from the general population, and their special problems need to be considered: such as the effect of hepatitis B virus (HBV) infection on the mother and fetus, the effect of pregnancy on replication of the HBV, whether mothers should take HBV antiviral therapy during pregnancy, the effect of these treatments on the mother and fetus, how to carry out immunization of neonates, whether it can induce hepatitis activity after delivery and other serious issues. At present, there are about 350 million individuals with HBV infection worldwide, of which 50% were infected during the perinatal or neonatal period, especially in HBV-endemic countries. Currently, the rate of HBV infection in thechild-bearing age group is still at a high level, and the infection rate is as high as 8.16%. Effective prevention of mother-to-child transmission is an important means of reducing the global burden of chronic HBV infection. Even after adopting the combined immunization measures, there are still 5%-10% of babies born with HBV infection in hepatitis B e antigen positive pregnant women. As HBV perinatal transmission is the main cause of chronic HBV infection, we must consider how to prevent this transmission to reduce the burden of HBV infection. In this population of chronic HBV infected women of childbearing age, specific detection, intervention and follow-up measures are particularly worthy of attention and discussion.

One-Year Outcomes of Women Started on Antiretroviral Therapy during Pregnancy before and after the Implementation of Option B+ in Malawi: A Retrospective Chart Review from Three Facilities

Objective: To compare one-year outcomes of women started on antiretroviral therapy (ART) during?pregnancy in the pre-Option B+ era to those in the Option B+ era. Methods: A retrospective chart review was performed at three sites in Malawi. Women were included in the “pre-Option B+” cohort if they started ART during pregnancy for a CD4 count 3?or WHO 3/4 condition and in the “Option B+” cohort if they started ART during pregnancy regardless of CD4 count or clinical stage. One-year outcomes were compared using Fisher’s exact and ANOVA F-tests. Results: A higher proportion of women in the pre-Option B+ cohort started ART at WHO stage 3/4 (11.9% versus 1.1%, P < 0.001), switched ART regimens (5.9% versus 0%, P = 0.002), or died in the first year after starting treatment (3.9% versus 0.5%, P = 0.05). While more women in the Option B+ cohort had poor adherence or defaulted, these differences were not significant. Conclusions: At our study sites, the transition to Option B+ has been associated with ART initiation in women with less advanced HIV infection, improved medication tolerability, and lower mortality. Further research is needed to better understand outcomes of Option B+.

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 antigenpositive 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.

Outcome Evaluation of Early Implementation of Option B+ in Cameroon: A Prospective Cohort Observational Survey in the Northwest and Southwest Regions

Background: Mother to child transmission (MTCT) of HIV constitutes a major source of new pediatric infections in Cameroon. Objective: The aim of this implementation research was to assess outcomes and effectiveness of providing life-long antiretroviral therapy (ART) for HIV-positive pregnant and breastfeeding women (Option B+). Methods: From October 2013 to July 2014, HIV-positive pregnant and breastfeeding women, not on antiretroviral (ARV) prophylaxis and ART, were recruited from 22 purposefully selected health facilities in the Northwest and Southwest regions for a prospective, observational cohort evaluation. Option B+ was offered to participants and outcome indicators were measured. Results: Out of 680 women eligible for this assessment, 669 (98%) were initiated on Option B+. Retention-in-care was 90% (95% CI, 87.85 - 92.61) and 79% (95% CI, 75.20 - 81.88), and loss to follow up (LTFU) was 7% (95% CI: 4.95 - 8.90) and 15% (95% CI: 12.06 - 17.56) at 6 and 12 months respectively. Maternal mortality at 12 months after ART initiation was 2% (13). As of March 2015, 538 HIV exposed infants (HEIs) were enrolled and received postpartum nevirapine prophylaxis within 72 hours of birth and 84% (454) were on cotrimoxazole at 6 to 8 weeks. By 8 weeks of age, 498 (93%) infants had HIV DNA PCR test with 486 (97.6%) negative and 12 (2.4%) positive. Conclusion: In Cameroon, successful implementation of Option B+ increased retention-in-care to 79% at one year for pregnant and breastfeeding women and reduced MTCT rate below 5% for HEIs at 8 weeks of age. Long term retention, maternal and infant mortality and final MTCT rate after cessation of breastfeeding require further evaluation.

Predictors of Non-Adherence to Combined Anti-Retroviral Therapy among Expectant and Breastfeeding Women Receiving Care through Test and Treat Model in Lusaka

Introduction: To achieve viral suppression and reduce vertical transmission of HIV, more than eighty percent of pregnant or breastfeeding women in Zambia have been started on combined ART using the Test and Treat model. However, Chawama First Level Hospital in Lusaka had records which showed that 32 percent of pregnant or breastfeeding women were non-adherent to combined anti-retroviral therapy (cART). Method: A mixed-method study was conducted to establish predictors of non-adherence to cART by women in the Test and Treat model of care. For the quantitative component, 92 consenting Pregnant and breastfeeding women were randomly drawn from ART defaulter register and a semi-structured questionnaire was administered. Multiple logistic regression was conducted to improve predictive power and control for confounders. Quantitative Results: The mean age was 28years. The study established that housewives were 84 percent less likely to be non-adherent [AOR 0.16;95% CI 0.12, 0.36] compared to women who were formally employed with a statistically significant P-value of 0.04. Pregnant or breastfeeding women who were several months away from home were 84.9 percent more likely to be non-adherent [AOR 15.11;95% CI 13.9, 16.4] compared to women who had travelled away from home for several days. The associated P-value was 0.03. The study also established that pregnant and breastfeeding women who were counselled in individually enclosed units were 91 percent less likely to be non-adherent compared to those who were counselled in an open space as a group [AOR 0.09;95% CI 0.02, 0.53] with an associated P-value of 0.01. Conclusion: The study established that predictors of non-adherence to cART among pregnant and breastfeeding women were: being a working-class client;being away from home or usual clinic for several months;being counselled in open spaces, and negative staff attitude. Therefore, researcher can conclusively say that predictors of non-adherence to cART can be solved by training and re-training of health workers in Patient-Centred Care Model for effective patient engagement. Women should be counselled in private rooms. Furthermore, an improvement in patient’s tracking system by the use of smart-care-cards for pregnant and breastfeeding women countrywide can reduce patient’s non-adherence to cART.

胎盘Hofbauer细胞介导的乙型肝炎病毒母婴垂直传播

目的探讨胎盘Hofbauer细胞在乙型肝炎病毒(HBV)经胎盘母婴垂直传播中的作用。方法外周血HBsAg和HBV-DNA均阳性孕妇175例,根据其新生儿外周血HBsAg及HBV-DNA检测结果,33例归为垂直传播组,142归为非垂直传播组;另选40例外周血HBsAg和HBV-DNA均阴性母亲及其新生儿作为对照组。应用光学显微镜、透射电镜和免疫组织化学技术观察胎盘Hofbauer细胞结构变化及其与HBV感染的关系。结果1.垂直传播组和非垂直传播组Hofbauer细胞散在分布于胎盘间质中,其超微结构发生改变;对照组胎盘组织中未发现Hofbauer细胞。2.垂直传播组胎盘Hofbauer细胞总数及结合HBV的Hofbauer细胞数明显高于非垂直传播组(P=0)。3.单个或多个病毒颗粒、病毒包涵体和病毒抗原颗粒仅出现在垂直感染组胎盘Hofbauer细胞胞质空泡和细胞间隙内。结论HBV可通过胎盘Hofbauer细胞介导HBV母婴垂直传播。

胎盘Hofbauer细胞在HBV母婴垂直传播的作用

目的探讨胎盘Hofbauer细胞在乙型肝炎病毒(HBV)母婴垂直传播的作用。方法垂直传播组(母亲及其新生儿血HBsAg和HBV-DNA均为阳性)、非垂直传播组(母亲血HBsAg和HBV-DNA阳性而新生儿阴性)和对照组(母亲及其新生儿血HBsAg和HBV-DNA均为阴性)各30例,透射电子显微镜观察其胎盘Hofbauer细胞超微结构变化及其与HBV颗粒的关系。结果①对照组未发现Hofbauer细胞:在垂直传播组和非垂直传播组,Hofbauer细胞散在分布于胎盘间质中。②在垂直感染组,Hofbauer细胞肿胀,胞浆突起减少,胞浆空泡变大;粗面内质网及高尔基复合体萎缩,线粒体缩小,溶酶体少见;胞核增大,染色质浓缩、边聚。在非垂直感染组,Hofbauer细胞呈圆形或卵圆形,细胞表面有大量胞浆突起,排列着微吞饮小体,细胞胞浆内有圆形空泡;线粒体呈杆状,峭排列紧密,溶酶体较多,高尔基体及粗面内质网欠发达;胞核偏位,核仁显著,染色质分布均匀。③在Hofbauer细胞胞质空泡、细胞间隙内存在单个或多个成熟病毒颗粒、病毒包涵体和病毒抗原颗粒。结论HBV可引起胎盘Hofbauer细胞超微结构改变,并经Hofbauer细胞介导引起母婴垂直传播。

HBV感染孕妇胎盘绒毛Hofbauer细胞并与HBV复制水平有关

目的探讨胎盘Hofbauer细胞在乙型肝炎病毒(HBV)垂直传播中的作用。方法以酶消化法、机械法、FicollHypaque分离法等多种方法分离纯化HBV感染孕妇流产绒毛Hofbauer细胞,CD163免疫组织化学染色鉴定Hofbauer细胞,PCR法检测绒毛Hofbauer细胞内HBV-DNA,实时定量PCR(qRT-PCR)检测Hofbauer细胞内CD16(FcγRⅢ)mRNA表达,免疫组织化学染色检测Hofbauer细胞CD16蛋白表达。结果 HBV感染孕妇流产绒毛Hofbauer细胞内HBV-DNA阳性率为31.67%(19/60),其中乙型肝炎e抗原阳性(HBe Ag+)和HBe Ag-孕妇绒毛Hofbauer细胞内HBV-DNA阳性率分别为46.4%(13/28)和18.75%(6/32)。qRT-PCR检测发现在HBV-DNA+的Hofbauer细胞内CD16 mRNA表达增加,其表达水平与HBV-DNA载量明显相关。免疫组织化学染色显示HBV-DNA+患者Hofbauer细胞胞膜和胞质CD16着色较HBV-DNA-者明显增强。结论 Hofbauer细胞作为胎盘巨噬细胞可被HBV感染,其感染率与体内病毒复制水平密切相关。

我国消除HBV母婴传播的实施案例与经验介绍

HBV母婴传播的减少是实现消除HBV的关键步骤。“乙肝母婴零传播工程”(“小贝壳”项目)于2015年7月在北京人民大会堂正式启动,是集科学防治和应用性研究于一体的公益项目,目的是通过移动医疗工具“小贝壳”手机应用软件对乙型肝炎孕妇进行规范化管理,以进一步减少甚至消除HBV母婴传播。目前,“小贝壳”项目已覆盖全国,为阻断HBV母婴传播提供了详细的实施策略、成功的实践经验及可靠的数据支持,对全球实现消除HBV母婴传播具有重要价值。本文详细介绍了4个典型案例的“小贝壳”项目实施策略及其成效,为进一步理解和阻断母婴传播提供了有力证据。

阻断HBV母婴传播:热点与难点

慢性HBV感染是我国最重要的公共卫生问题之一,HBV感染人群超过7000万,防控工作面临着严峻挑战。当前政府及社会各界正在加速推进“2030年实现消除病毒性肝炎对公众健康的威胁”的宏伟目标。母婴传播是HBV最主要的传播途径,因此,做好HBV母婴阻断是消除病毒性肝炎的关键一环。目前在该领域存在一些热点与难点问题亟需解决,包括妊娠期采用富马酸丙酚替诺福韦长期治疗的安全性、妊娠早期抗病毒治疗的安全性、无免疫球蛋白策略的有效性和HBV经生殖细胞传播的风险等,解决这些问题对进一步推进HBV母婴阻断工作,加快我国实现2030年目标的进程具有重要作用。