乙型肝炎病毒e抗原阳性孕妇所生婴儿联合免疫接种后乙型肝炎病毒血清学标志物的动态变化

目的 观察HBeAg阳性且HBV DNA高载量孕妇所生婴儿用乙型肝炎疫苗联合免疫接种后的母婴阻断效果及HBV血清学标志物的动态变化.方法 回顾性分析HBeAg阳性且HBVDNA≥106拷贝/ml孕妇127例,婴儿出生后即刻及第15天于臀大肌注射高效价乙型肝炎免疫球蛋白200 IU,出生时与第1、6个月于右上臂肌肉注射乙型肝炎疫苗20μg,随访其婴儿至12个月龄.用酶联免疫吸附法及荧光定量PcR检测婴儿出生时及第1、7、12个月时的HBV血清学标志物和HBV DNA载量,观察婴儿出生时HBV血清学标志物模式、母婴传播率、疫苗接种后的HBV宫内感染率、抗-HBs阳性保护率及HBV血清学标志物动态变化.结果 127例孕妇分娩婴儿均为单胎,出生时29例婴儿HBsAg为阳性,其中11例合并HBV DNA阳性,母婴垂直传播率为22.83％.随访至1个月,10例婴儿合并HBV DNA阳性从而发生HBV宫内感染,表现为HBsAg、HBeAg及抗-HBc均为阳性.2例婴儿HBsAg弱阳性,伴有抗-HBs滴度的产生,后续随访中均转阴,乙型肝炎宫内感染率为7.87％.非宫内感染婴儿出生时HBeAg及抗-HBc阳性率分别为96.58％和98.29％,免疫接种后婴儿HBeAg及抗-HBc逐步转阴,均未产生抗-Hbe.非宫内感染婴儿均产生有效乙型肝炎保护性抗体,乙型肝炎疫苗及高效价乙型肝炎免疫球蛋白联合免疫接种后,婴儿抗-HBs滴度从出生至12个月龄逐步上升,母源性HBeAg滴度逐步下降以至转阴.结论 乙型肝炎疫苗联合高效价乙型肝炎免疫球蛋白免疫接种能明显降低HBV母婴传播,增强婴儿乙型肝炎表面抗原保护性抗体,体内母源性HBeAg及抗-HBc亦随之降低甚至转阴.     

HBsAg和HBeAg(或抗-HBe)阳性孕妇血清中的乙型肝炎病毒DNA

最近,对于乙型肝炎表面抗原(HBsAg)和乙型肝炎e抗体(抗-HBe)阳性母亲所产婴儿是否需要进行被动或主动免疫存在着争论。由于有一定数量的抗-HBe阳性母亲可通过垂直传播将乙型肝炎病毒(HBV)传染给婴儿,因此作者对44例HBsAg阳性孕妇的血清进行了HBV-DNA检测,后者可作为HBV传播的一个指标。以克隆的HBV-DNA pCp10为探针进行斑点杂交试验。结果7例HBeAg阳性血清标本中有6例(86%)HBV-DNA呈强阳性,其中3例血清DNA多聚酶和HBV-DNA同时阳性;在33例抗-HBe阳性血清标本中也有8例(24%)可检出HBV-DNA;在4例HBeAg和抗-HBe(RIA法)均阴性的血清中有2例检出了HBV-DNA。未观察到HBeAg阴性血清中可检出DNA多聚酶活性。 HBsAg滴度(1∶10~3～1∶10~5)和转氨酶水平均     

乙型肝炎的母婴传播及其阻断

流行病学调查研究表明,乙型肝炎病毒(HBV)从无症状携带乙型肝炎表面抗原(HBsAg)的母亲传播到其婴儿是造成大量HBsAg携带者的重要因素,约40%HBsAg慢性携带者是由母婴传播所致。各地人群的母婴传播率可有较大差异。Beasley在台湾对105例HBsAg阳性母亲的婴儿进行了平均17.5个月的随访,发现40例(38.1%)有HBV感染的证据,尤以乙型肝炎e抗原(HBeAg)阳性母亲的母婴传播率最高,已超过90%。国内患乙型肝炎或携带HBsAg母亲的婴儿1年     

陕西地区孕妇HBV感染现状与母婴传播的危险因素

目的调查陕西省孕妇HBV感染率并筛选母婴传播高危人群。方法自2010年-2015年连续调查了陕西省18家医院13 451名孕妇HBV感染情况,对所有HBs Ag阳性孕妇所生婴儿进行联合免疫,采用单因素及多因素logistic回归分析母婴传播的高危因素。计量资料组间比较采用t检验或Mann-Whitney U检验。计数资料多组间比较采用χ2检验。结果陕西省孕妇HBsAg流行率为7. 07%,陕南地区高达9. 40%。HBV母婴传播率为5. 21%,单因素分析显示母亲HBsAg滴度、HBeAg滴度、HBeAg阳性及HBV DNA载量与婴儿HBV感染相关,多因素分析显示母亲HBV DNA载量是母婴传播的独立危险因素(相对危险度:1. 586,95%可信区间:1. 020～2. 465,P=0. 041)。发生母婴传播的HBV感染孕妇中,84. 62%为HBeAg阳性且HBV DNA 106IU/ml;发生母婴传播的婴儿15. 38%来自于HBeAg阴性的HBV感染孕妇。HBeAg阳性且HBV DNA 10~6IU/ml的孕妇中,婴儿发生母婴传播的相对危险度为1. 210(1. 129～1. 297);而HBeAg阴性,但HBV DNA 2×103IU/ml且HBsAg 104IU/ml的孕妇中,婴儿发生母婴传播的相对危险度为26. 062(2. 633～258. 024)。结论陕西省孕妇HBV感染率仍高,HBeAg阳性且高病毒载量孕妇发生母婴传播风险较高; HBeAg阴性母亲所生婴儿HBV感染率虽然低,但当母亲HBV DNA 2×103IU/ml且HBsAg 104IU/ml时仍有较高母婴传播的风险。     

基于社区人群的慢性乙型肝炎病毒感染孕妇产前血清学及病毒学特征北大核心CSCD

目的了解中国部分地区基于社区人群的未经抗病毒治疗的乙型肝炎(乙肝)病毒(HBV)表面抗原(HBsAg)阳性孕妇产前HBV血清学和病毒学特点。方法该研究从广西、江苏、河南地区入组1741例HBsAg阳性孕妇。所有孕妇的临产前血清样本采用Abbott Architect i2000和Abbott Architect m2000分别检测HBV血清学标志物及HBV DNA水平;采用型特异性引物巢式聚合酶链反应(n PCR)法进行HBV基因型分型。结果 1741例HBsAg阳性孕妇中,HBeAg阳性占37.0%(645/1741),HBeAg阴性孕妇占63.0%(1096/1741)。HBeAg阳性孕妇产前HBsAg滴度、HBV DNA水平以及B基因型孕妇所占比例均高于HBeAg阴性孕妇,但年龄低于HBeAg阴性孕妇。HBeAg阳性孕妇的HBsAg滴度和HBV DNA水平呈正相关(r=0.790,P<0.001),HBeAg滴度和HBV DNA水平也呈正相关性(r=0.564,P<0.001)。而HBeAg阴性孕妇的HBsAg滴度和HBV DNA水平无相关性(r=0.020,P=0.517)。结论未经抗病毒治疗的HBsAg阳性孕妇在不同HBeAg状态下,血清HBV DNA水平及HBsAg滴度分布各不相同。对于HBeAg阳性孕妇人群,HBeAg滴度、HBsAg滴度可能成为HBV DNA水平的替代指标。     

基于社区人群的慢性乙型肝炎病毒感染孕妇产前血清学及病毒学特征

目的了解中国部分地区基于社区人群的未经抗病毒治疗的乙型肝炎(乙肝)病毒(HBV)表面抗原(HBsAg)阳性孕妇产前HBV血清学和病毒学特点。方法该研究从广西、江苏、河南地区入组1741例HBsAg阳性孕妇。所有孕妇的临产前血清样本采用Abbott Architect i2000和Abbott Architect m2000分别检测HBV血清学标志物及HBV DNA水平;采用型特异性引物巢式聚合酶链反应(n PCR)法进行HBV基因型分型。结果 1741例HBsAg阳性孕妇中,HBeAg阳性占37.0%(645/1741),HBeAg阴性孕妇占63.0%(1096/1741)。HBeAg阳性孕妇产前HBsAg滴度、HBV DNA水平以及B基因型孕妇所占比例均高于HBeAg阴性孕妇,但年龄低于HBeAg阴性孕妇。HBeAg阳性孕妇的HBsAg滴度和HBV DNA水平呈正相关(r=0.790,P0.001),HBeAg滴度和HBV DNA水平也呈正相关性(r=0.564,P0.001)。而HBeAg阴性孕妇的HBsAg滴度和HBV DNA水平无相关性(r=0.020,P=0.517)。结论未经抗病毒治疗的HBsAg阳性孕妇在不同HBeAg状态下,血清HBV DNA水平及HBsAg滴度分布各不相同。对于HBeAg阳性孕妇人群,HBeAg滴度、HBsAg滴度可能成为HBV DNA水平的替代指标。     

慢性乙型肝炎患者血清前S1抗原与血清HBV DNA和HBeAg 的关系探讨

目的：探讨 HBV 前 S1抗原与血清 HBV DNA 和 HBeAg 的关系。方法选择我院收治的100例慢性乙型肝炎患者,采用双抗体夹心 ELISA 法检测 HBV 前 S1抗原,常规检测 HBV DNA 和 HBeAg。结果在100例 CHB 患者中,血清前 S1抗原阳性88例（88.0%）,血清 HBV DNA 阳性71例（71.0%）,前 S1抗原阳性率显著高于 HBV DNA （x2=5.358,P＜0.05）;100例患者HBV DNA 和前 S1抗原两者均阳性或均阴性者共69例（69.0%）,而在血清 HBV DNA 阳性者中血清前 S1抗原阴性率为9.9%（7/71）,在血清前S1抗原阳性者中,血清 HBV DNA 阴性率为27.3%（24/88）;血清前 S1抗原与 HBeAg 同时阳性或阴性者共33例（33.0%）,而在血清 HBeAg 阳性者中,前 S1抗原阴性率为21.6%（8/37）,在前 S1抗原阳性者中,HBeAg 阴性率为67.0%（59/88）。结论在慢性乙型肝炎患者,前 S1抗原可能比血清 HBV DNA 和 HBeAg 有更高的阳性率。     

乙型肝炎病毒载量与抗原抗体模式的关系

目的探讨乙型肝炎病毒载量与抗原抗体模式的关系,为乙型肝炎的诊治、预防提供科学依据. 方法用实时荧光定量聚合酶链反应和ELISA检测HBV DNA和抗原抗体,统计分析不同抗原抗体模式的HBV DNA量. 结果在HBsAg和HBeAg阳性模式中,HBV DNA拷贝数＞103/ml者占87.3%,其中＞107/ml者占66.7%;在HBsAg阳性,抗-HBe阳性模式中,HBV DNA拷贝数＜103/ml者占74.5%,＞107/ml者占8.3%;在HBsAg阳性,抗-HBc阳性模式中,HBV DNA拷贝数＞103/ml者占48.0%,＞107/ml者占29.1%.HBeAg阳性模式HBV 载量显著高于HBeAg阴性模式(P＜0.01).抗-HBe阴性模式HBV载量显著高于抗-HBe阳性模式(P＜0.01).在HBsAg阴性模式中,HBV DNA拷贝数＞103/ml占7.9%,1例拷贝数高达1.59×109/ml. 结论 HBeAg阳性模式HBV 载量显著高于HBeAg阴性模式,抗-HBe 阴性模式病毒载量显著高于抗-HBe阳性模式,HBeAg阳性模式中的少数人HBV载量很低,HBeAg阴性模式中少数人HBV载量很高,HBsAg阴性模式中少数人存在病毒复制,因此,对于一具体患者来说,根据抗原抗体模式,难以准确地判断病毒复制程度及其传染性的强弱.     

40岁以上HBeAg阳性和阴性慢性乙型肝炎病毒感染者的临床特点比较

目的探讨40岁以上HBeAg阳性和HBeAg阴性慢性HBV感染者的临床特点。方法收集40岁以上慢性HBV感染者共186例,其中HBeAg阳性组93例,HBeAg阴性组93例。结果 40岁以上HBeAg阳性慢性HBV感染者男性为多(76.34%),并且多有乙型肝炎家族聚集现象(78.49%);40岁以上HBeAg阳性慢性HBV感染者的HBV DNA水平与ALT水平均高于HBeAg阴性慢性HBV感染者;40岁以上乙型肝炎肝硬化患者中,HBeAg阳性者占少数;40岁以上乙型肝炎肝硬化失代偿期患者中,HBeAg阳性者多合并腹水形成,而HBeAg阴性者既可见腹水形成,又可见上消化道出血。结论 40岁以上HBeAg阳性慢性HBV感染者多见于男性,多具有家族聚集现象,HBeAg阳性肝硬化患者所占比率较低,但HBV DNA水平较高,肝脏的炎症活动明显,病情进展可能较快。     

HBsAg阳性母亲新生儿树突状细胞数量变化的影响因素

目的 探讨HBsAg阳性母亲新生儿树突状细胞(DC)数量变化的影响因素.方法 收集2011年7月至2012年3月在太原市第三人民医院妇产科分娩的HBsAg阳性孕妇及其新生儿60对.流式细胞术测定新生儿DC亚群数量,化学发光免疫试验检测母亲及新生儿出生24 h内、主被动免疫前的外周血HBV血清学标志物,荧光定量PCR检测HBV DNA.两组样本比较采用两独立样本秩和检验中的Mann-Whitney检验和t检验,相关分析采用Spearman秩相关分析和卡方检验.结果 60名新生儿中,5名为HBsAg阳性、HBV DNA阴性;60例HBsAg阳性孕妇中,HBeAg阳性21例,HBV DNA阳性29例.HBV宫内感染组新生儿外周血髓样DC (mDC)、浆细胞样DC(pDC)与非感染组比较,差异无统计学意义(Z=-0.535,Z=-0.027;均P＞0.05).母亲HBeAg阳性与新生儿HBeAg阳性密切相关(Pearson列联系数为0.928,P＜0.01).HBeAg阳性和HBeAg阴性母亲所生新生儿外周血mDC分别为0.60±0.57和0.87±0.58(Z=-2.085,P＜0.05).HBV DNA阳性母亲所生新生儿外周血mDC、pDC与HBV DNA阴性者比较,差异无统计学意义(均P＞0.05);母亲外周血HBV DNA＞1×107拷贝/mL与≤1×103拷贝/mL比较时,其新生儿外周血pDC明显下降(0.30±0.18比0.64±0.55,t=-2.996,P=0.005).结论 母亲HBeAg阳性可能使新生儿mDC数量下降,而HBV DNA＞1×10 7拷贝/mL时,可能会使新生儿pDC数量减少.     

60例孕妇HBV血清标志物水平与母婴传播的关系分析

目的 探讨孕妇乙型肝炎病毒（HBV）血清标志物水平与母婴传播的关系。方法 采取60例孕妇、脐带、新生儿血清用美国雅培试剂做HBV血清标志物（HBVM）包括：HBsAg、HBsAb、HBeAg、HBeAb、HBcAb定量分析,用荧光定量PCR法测HBV DNA。结果 HBsAg、HBeAg、HBcAb阳性母亲的新生儿脐血HBV M阳性率91．67％,新生儿血HBV M阳性率85％,母血HBsAg、HBeAg、HBcAb滴度显著高于脐血、新生儿血,且母血、脐血、新生儿血HBV M水平依次降低;HBV DNA阳性率也依次降低,分别为58、33％、10％、6、67％,滴度也依次降低。HBsAg、HBeAb、HBcAb阳性母亲,HBsAg、HBcAb阳性母亲和单项HBsAg阳性母亲的新生儿脐血、新生儿血HBV M阳性率较低。新生儿血以HBeAg阳性为主,滴度明显高于正常值,HBsAg滴度仅略高于正常值。结论 母婴垂直传播与母亲HBeAg高滴度有密切关系,与母亲HBV DNA阳性或阴性关系并不十分密切。检测脐血和新生儿血HBsAg、HBV DNA阴性并不能排除HBV感染,不如检测HBsAg、HBeAg更有意义,更经济。     

乙型肝炎表面抗原和乙型肝炎e抗原双阳性的乙型肝炎病毒携带产妇进行母乳喂养的安全性

目的探讨乙型肝炎表面抗原(hepatitis B surface antigen,HBsAg)和乙型肝炎e抗原(hepatitis B e antigen,HBeAg)双阳性的乙型肝炎病毒(hepatitis B virus,HBV)携带产妇采用母乳喂养对其所生婴儿HBV感染率的影响.方法采用前瞻性队列研究方法,纳入2016年2月至2018年5月在浙江大学医学院附属妇产科医院进行产前检查及分娩的HBsAg和HBeAg双阳性携带HBV产妇及其所生的婴儿各323例,将其分为母乳喂养组和人工喂养组.采用化学发光免疫分析法和聚合酶链反应-荧光探针法,分别检测两组婴儿在出生<24 h及7月龄时的血清HBV标志物和HBV DNA的阳性率.统计学方法采用x2检验.结果最终纳入297例患者,其中母乳喂养组149例,人工喂养组148例.母乳喂养组与人工喂养组婴儿在出生<24 h及7月龄时的HBsAg、抗-HBs、HBeAg、HBV DNA>100 IU/mL的阳性率比较,差异均无统计学意义(均P>0.05).母乳喂养组出生<24 h新生儿抗-HBs阳性率为58.39%(87/149),低于7月龄时的95.97%(143/149);母乳喂养组出生<24 h新生儿HBeAg阳性率为65.10%(97/149),高于7月龄时的13.42%(20/149);差异均有统计学意义(x2=59.75、40.49,均P<0.01).母乳喂养组出生<24 h新生儿的HBsAg和HBV DNA>100 IU/mL阳性率分别为2.01%(3/149)和2.68%(4/149),其7月龄时的HBsAg和HBV DNA>100 IU/mL阳性率分别为2.68%(4/149)和2.68%(4/149),两个时间点比较差异均无统计学意义(均P>0.05).人工喂养组出生<24 h新生儿抗-HBs阳性率为47.97%(71/148),低于7月龄时的95.94%(142/148);人工喂养组出生<24 h新生儿HBeAg阳性率为55.41%(82/148),高于7月龄时的19.59%(29/148);差异均有统计学意义(x2=85.37、39.84,均P<0.01).人工喂养组出生<24h新生儿的HBsAg和HBV DNA>100IU/mL阳性率分别为4.73%(7/148)和1.35%(2/148),其7月龄时的HBsAg和HBV DNA>100 IU/mL阳性率分别为1.35%(2/148)和1.35%(2/148),两个时间点比较差异均无统计学意义(均P>0.05).结论母乳喂养不是增加HBsAg和HBeAg双阳性HBV携带产妇垂直传播风险的决定性因素,建议这类产妇在正规预防的前提下进行母乳喂养.     

Relationship between HBV viremia level of pregnant women and intrauterine infection:neated PCR for detection of HBV DNA

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Missed opportunities for prevention of perinatal transmission of hepatitis B: A retrospective cohort study

BACKGROUND:

Perinatal transmission of hepatitis B virus (HBV) can occur despite postexposure prophylaxis (PEP). Recent literature suggests that antiviral treatment during pregnancy when maternal HBV DNA levels are elevated can further decrease vertical transmission. However, HBV DNA screening is not routinely performed antenatally.

OBJECTIVE:

To determine the rates of HBV prevalence and perinatal transmission in an antenatal cohort.

METHODS:

A retrospective review of public health records (December 2008 to December 2010) was performed for both mothers and newborns.

RESULTS:

A total of 725 mother-infant pairs were included. Of these, 574 of 715 (80%) women had antenatal hepatitis B e antigen (HBeAg) testing performed, and 127 of 574 (22%) were HBeAg positive (HBeAg+). Of babies born to hepatitis B surface antigen-positive (HBsAg+) mothers, only 573 of 725 (79%) received complete PEP. In addition, 172 of 725 (24%) infants did not receive post-PEP blood testing or were lost to follow-up. Of the 552 infants with results available, seven cases (1.3%) of mother-to-child HBV transmission were observed, six of which involved infants born to HBeAg+ women.

CONCLUSIONS:

Our findings suggest that routine HBeAg screening could identify a subset of mother-infant pairs among HBsAg+ pregnant women who are at higher risk for vertical HBV transmission. Determination of viral load in expectant HBeAg+ mothers may provide more precise insight into HBV transmission to their infants.     

A randomized controlled clinical trial： Interruption of intrauterine transmission of hepatitis B virus infection with HBIG

AIM: To evaluate the efficacy of interruption of intrauterine infection of HBV with HBIG in pregnant women with positive HBeAg and HBsAg. METHODS: A prospective randomized controlled trial was adopted. Sixty cases with positive HBeAg and HBsAg were coincident with the criteria of inclusion, and 8 cases were excluded. Fifty-two cases were analyzed (28 cases in trial group and 24 in control group). All cases in trial group received 200 IU HBIG intravenously every 4 wk for 3 times from the 28th wk. The cases of control group received placebo in the same way. All pregnant women were detected for HBeAg and HBV-DNA at the beginning of the trial and end of the trial (delivery). The cord blood of all newborns were collected for detecting HBeAg and HBV-DNA simultaneously. RESULTS: For investigation of HBeAg of newborns in trial group, 6 of 28 cases of newborns had positive HBeAg, the HBeAg positive rate being 21.4%, the total rate of 95% CI being 8%-41%. In control group, 19 of 24 cases of newborns had positive HBeAg, HBeAg positive rate was 79.2%, the rate of 95%CI being 5%-93%. By statistical analysis, x2 = 17.26, P < 0.01, RR = 0.27, 95% CI (6.3×10-6, 8.6×10-5). For investigation of HBV-DNA of newborns in trial group, 7 of 28 cases of newborns had positive HBV-DNA, HBV-DNA positive rate being 25%, the total rate of 95% CI being ll%-45%. In control group, 20 of 24 cases of newborns had positive HBV-DNA, HBV-DNA positive rate was 83.3%, the total rate of 95% CI being 63%-95%. By statistical analysis, x2 = 17.62, P < 0.01, RR = 0.30, 95% CI (1.5×10-5, 1.7×10-4). The results indicated that there was significant difference in HBeAg positive rate and HBV-DNA positive rate of newborns between the two groups. In trial group, 7 of 28 newborns had HBV-DNA positive, but the HBV-DNA load of newborns was lower than that of their mothers. In control group, 20 of 24 newborns still had HBV-DNA positive, and the HBV-DNA load of newborns was close to those of their mothers. Statistical analysis indicated that there was no significant difference in HBV-DNA load between postnatal women without HBIG intervention and their filial generations (T = 81.5, P > 0.1). CONCLUSION: It is effective and safe to prevent in-trauterine infection of HBV with HBIG from the 28th wk in pregnant women with positive HBeAg and HBsAg. In clinical application, those pregnant women with negative HBeAg and positive HBV-DNA also need to be interrupted by HBIG.     

母亲血清乙型肝炎表面抗原、e抗原滴度与新生儿接种乙型肝炎疫苗免疫失败的关系

目的 研究孕妇血清乙型肝炎表面抗原（HBsAg）、乙型肝炎e抗原（HBeAg）滴度与其新生儿接种乙型肝炎（乙肝）疫苗发生免疫失败的关系,探讨能否用孕妇血清HBsAg、HBeAg滴度代替血清HBV DNA浓度来衡量新生儿接种乙肝疫苗后发生免疫失败的危险性。方法 178例HB-sAg、HBeAg双阳性母亲的新生儿接种乙肝疫苗后,随访至24月龄,32例发生免疫失败,用斑点杂交法检测孕妇临产前血清乙型肝炎病毒（HBV）DNA浓度、用酶联免疫吸附试验（ELISA）法测定孕妇HBsAg和HBeAg浓度,研究孕妇HBsAg、HBeAg的滴度与其新生儿接种疫苗发生免疫失败的关系,并与孕妇血清HBV DNA浓度与其新生儿发生免疫的关系相比较。结果 随着母亲血清HB-sAg、HBeAg滴度的升高,其新生儿发生免疫失败的危险性升高,当孕妇血清HBsAg滴度≥1:1000、HBeAg≥1:100时,分别有26.3%、31.4%的新生儿发生乙型疫苗免疫失败,与当孕妇血清HBV DNA浓度≥125pg/ml,新生儿发生免疫失败的危险性相当。结论 孕妇血清HBsAg、HBeAg高滴度与其新生儿接种疫苗发生免疫失败有密切联系,孕妇血清HBsAg滴度≥1:1000、HBeAg滴度≥1：100能够代替血清HBV DNA浓度≥125pg/ml作为衡量孕妇的乙肝高传染性的指标来预测新生儿发生免疫失败的危险性。     

Factors associated with vaccine failure and vertical transmission of hepatitis B among a cohort of Canadian mothers and infants

Summary. Mother‐to‐child transmission of hepatitis B virus (HBV) continues to occur despite immunoprophylaxis. We examined maternal factors contributing to transmission in infants receiving adequate immunoprophylaxis in Alberta, Canada. Prenatal specimens from HBsAg‐positive women whose babies developed HBV infection despite immunoprophylaxis (cases) and HBsAg‐positive mothers whose babies did not (controls) were tested for HBsAg, HBeAg and HBV DNA. Specimens with detectable DNA underwent HBV genotyping. Routinely collected surveillance data and laboratory test results were compared between cases and controls. Twelve cases and 52 controls were selected from a provincial registry from 2000 to 2005. At the time of prenatal screening, median maternal age was 31 years [interquartile range (IQR): 27.5–34.5], and median gestational age was 12 weeks (IQR 10.0–15.5). Cases were more likely than controls to test positive for HBeAg (77.8%vs 23.1%; P < 0.05). Of all mothers with detectable viral load (n = 51), cases had a significantly higher median viral load than did controls (5.6 × 10⁸ IU/mL vs 1750 IU/mL, P < 0.0001). Of the two cases who were HBeAg negative, one had an undetectable viral load 8 months prior to delivery and a sP120T mutation. The viral load in the other case was 14 000 IU/mL. The majority of isolates were genotype B (31.3%) and C (31.3%) with no significant differences in genotype between cases or controls. In this case–control study, transmission of HBV to infants was more likely to occur in mothers positive for HBeAg and with high HBV DNA.     

Hepatitis B immunoglobulin (HBIG) efficacy in the prevention of perinatal transmission of hepatitis B virus (HBV) infection

Twelve out of 13 infants born from mothers having both HBsAg and HBeAg developed HBV carrier state within 4 months after birth. On the other hand, no babies from mothers having HBsAg and anti-HBe developed HBV carrier state. In order to prevent perinatal transmission of HBV, HBIG was administered into 14 babies born from mothers with positive HBeAg three or four times during 6 months after birth. During 12 months or more of observation period 5 out of 14 infants who received HBIG acquired active anti-HBs response after discontinuation of HBIG (passive-active immunization). However, 3 out of 14 infants unfortunately developed persistently positive HBsAg antigenemia at 12th, 14th and 14th month respectively after birth. Remaining 6 babies still have no virus markers, indicating not infected. These results indicates that HBIG administration was extremely effective for prevention of perinatal transmission of HBV. However, additional preventive measures with active immunization (HBV vaccine) seems to be necessary to prevent completely the perinatal transmission of HBV.     

Virologic factors associated with failure to passive-active immunoprophylaxis in infants born to HBsAg-positive mothers

In infants born to hepatitis B surface antigen (HBsAg)-positive mothers, failure after passive-active immunization still occurs. The role of maternal hepatitis B DNA level and other risk factors in this setting remains unclear. This study retrospectively evaluated virologic and other risk factors associated with immunoprophylaxis failure in infants born to HBsAg-positive mothers. Between January 2007 and March 2010, we reviewed the clinical and virologic tests in 869 mother-infant pairs. All infants received the identical passive-active immunization schedule after birth. The failure infants (HBsAg positive at 7-12 months of age) were compared to infants who were HBsAg negative when tested during this time period. Among 869 infants, 27 (3.1%) infants were immunoprophylaxis failures and the other 842 (96.9%) infants remained HBsAg negative. When mothers' pre-delivery HBV DNA levels were stratified to <6, 6-6.99, 7-7.99 and ≥ 8 log(10) copies/mL, the corresponding rates of immunoprophylaxis failure were 0%, 3.2% (3/95), 6.7% (19/282) and 7.6% (5/66), respectively (P < 0.001 for the trend). All failure infants were born to hepatitis B e antigen (HBeAg)-positive mothers. Multivariate logistic regression analysis identified maternal HBV DNA levels [odds ratio (OR) = 1.88, 95% confidence interval (CI): 1.07-3.30] and detectable HBV DNA in the cord blood (OR = 39.67, 95% CI: 14.22-110.64) as independent risk factors for immunoprophylaxis failure. All failure infants were born to HBeAg-positive mothers with HBV DNA levels ≥ 6 log(10) copies/mL. The presence of HBV DNA in cord blood predicted failure to passive-active immunization.