不同联合免疫策略对乙型肝炎病毒高载量孕妇所生婴儿抗-HBs水平的影响

目的 比较HBeAg阳性且HBV DNA高载量孕妇所生婴儿出生后应用不同剂量的乙型肝炎免疫球蛋白(HBIG)及乙型肝炎疫苗(HBVac)联合免疫接种后的母婴阻断效果,新生儿抗-HBs水平的差异. 方法 随机选取2009年至2013年我院产前检查并足月分娩的HBeAg阳性且建卡及临产均HBV DNA＞1×106 IU/ml孕妇所生婴儿118例,婴儿出生后抽血检查HBV标志物和HBVDNA定量,据产妇及家属意愿抽血后按注射HBIG及HBVac剂量的不同分为3组:A组:58例,予HBIG 200 IU及HBVac 20 μ g肌肉注射;B组:35例,予HBIG 200 IU及HBVac 10 μg肌肉注射;C组:25例,予HBIG 100 IU及HBVac 20 μg肌肉注射,随访至7月龄.婴儿出生至7月龄的HBsAg、抗-HBs、HBeAg、HBV DNA变化采用重复测量方差分析;组间比较采用x2检验,P＜ 0.05为差异有统计学意义.结果 除去5例宫内感染婴儿,113例婴儿免疫接种后均产生抗-HBs.完成HBIG注射后,A、B、C三组1月龄婴儿时抗-HBs滴度分别为(263.56±50.98) mIU/ml、(231.06±74.07) mIU/ml和(99.23±29.82) mIU/ml,C组分别与A、B组比较,t值分别为15.01、8.41,P值均＜0.001,差异均有统计学意义.A、B、C三组7月龄时婴儿抗-HBs滴度分别为(788.10±281.96) mIU/ml、(428.39±347.48) mIU/ml和(708.44±315.69) mIU/ml,B组与A、C组比较,t值分别为5.45、3.19,P值均＜0.05,差异均有统计学意义. 结论 HBeAg阳性高病毒载量孕妇所生非宫内感染儿出生后应用HBIG及HBVac免疫接种能获得较好的免疫保护,应用HBIG 200 IU较100 IU,HBVac 20 μg较10 μg更安全可靠.     

HBsAg阳性的1355名孕妇乙型肝炎病毒母婴传播的随访调查

目的 观察HBsAg阳性孕妇所分娩婴儿的HBV感染情况.方法 前瞻性收集血清HBsAg阳性孕妇1355名及其所分娩的新生儿1360名(包括5名双胎)的资料,所有新生儿均于出生6h内注射乙型肝炎免疫球蛋白200U,并按0-1-6方案接种重组酵母乙型肝炎疫苗10μg,随访新生儿至12月龄,检测0、7、12月龄婴儿外周血HBV血清学标志物和HBV DNA定量.定量资料采用t检验,定性资料采用卡方检验、秩和检验或Fisher确切概率法.结果 1360名婴儿随访至12月龄时,21名发生HBV感染,总的宫内感染率为1.54％.其中母亲为HBeAg阳性者的宫内感染率为4.44％,HBeAg阴性者未发生宫内感染(x2=35.99,P＜0.05);母亲为HBV DNA阳性者的宫内感染率为3.13％,阴性者也未发生宫内感染(x2=21.84,P＜0.05).母亲血清HBV DNA≥1×107IU/mL者的宫内感染率为6.01％,较HBV DNA＜1×107IU/mL者明显升高(x2=39.43,P＜0.05).结论 新生儿经严格的主-被动联合免疫后,仍存在HBV的宫内感染.其中母亲为HBeAg阳性者及HBV DNA高复制水平者的宫内感染率明显增高;宫内感染是导致HBV母婴传播免疫阻断失败的主要原因.     

拉米夫定对乙型肝炎病毒母婴传播的影响及安全性

目的 评价妊娠中期应用拉米夫定对HBV传播的影响及安全性,寻求最佳预防宫内传播的方法.方法 拉米夫定组57例孕妇于孕20～26周开始服用拉米夫定100 mg/d至分娩后,乙型肝炎免疫球蛋白(HBIG)组66例孕妇于孕28周开始使用HBIG 200 IU行宫内阻断治疗,2组新生儿出生均予主、被动联合免疫,观察新生儿宫内感染发生情况、抗病毒疗效及母婴异常情况,随访到婴儿1岁并分别在0、1、7、12个月龄时监测其血清HBV DNA、HBsAg和抗-HBs定量变化.数据行f检验和χ~2检验.结果 拉米夫定组孕妇于分娩前HBV DNA显著下降(t=18.72,P<0.05),转阴率为33.3%,肝功能异常者全部恢复正常.该组57例新生儿随访至1月龄时HBsAg或HBVDNA均阴性,宫内感染率为0,与HBIG组宫内感染率(15.2%)相比,差异有统计学意义(χ~2=9.40,P<0.05).2组婴儿1岁时的血清抗-HBS水平无差异(t=0.71,P>0.05),拉米夫定组HBV慢性感染为0,HBIG组10例宫内感染婴儿均为HBsAg、HBeAg、抗-HBc、HBV DNA阳性,2组孕妇及婴儿均未发现不良反应.结论 对于HBV水平较高孕妇,妊娠中期采用拉米夫定降低病毒含量,阻断HBV母婴垂直传播(宫内传播及产时传播)是行之有效的.     

拉米夫定阻断HBV母婴传播疗效及安全性的系统评价

我国是HBV感染高发区,育龄妇女HBV携带率高,在没有任何阻断措施下,HBsAg阳性孕妇所生婴儿40％～70％将成为HBsAg携带者;而HBsAg、HBeAg双阳性的孕妇,婴儿自然感染率可达90％[1].并且宫内感染与孕母HBV DNA正相关,当孕母HBV DNA≥108拷贝/mL时,宫内感染率＞80％,而当HBV DNA＜104拷贝/mL时,宫内感染低至6％以下[2].当前,HBV母婴阻断措施主要是婴儿出生后实施联合免疫[乙型肝炎疫苗(Vaccine)及高效价乙型肝炎免疫球蛋白( HBIG)].尽管联合免疫已经使我国人群中HBsAg阳性率下降了2.57％,然而主、被动免疫并不能完全阻断HBV母婴传播,尤其对HBV载量高的孕母.当孕母HBV DNA＞ 108拷贝/mL时,单用乙型肝炎疫苗婴儿免疫失败率为40％,即使和HBIG联用免疫失败率也达25％.     

304例阻断HBV母婴传播效果观察

目的:探讨乙肝疫苗(HepB)和高效价乙肝免疫球蛋白(HBIG)联合(以下称主被动免疫)阻断HBV母婴传播效果.方法:将宁夏平罗县304例血清HBsAg阳性孕妇及其所生婴儿作为研究对象,按孕妇血清HBeAg定性结果分为阳性组、阴性组,并对阻断结果进行分析.结果:经主被动免疫方法阻断HBV母婴传播,孕妇HBeAg阴性组阻断率达100%,HBeAg阳性组阻断率达96.51%(P＜0.05),总体阻断率达98.63%.经主被动免疫后,孕妇HBeAg阳性组婴儿12月龄抗-HBs阳转率为53.85%(56/104),孕妇HBeAg阴性组婴儿12月龄抗-HBs阳转率为58.00%(116/200)(P＞0.05),两组婴儿12月龄抗-HBs总体阳转率为56.57%.分娩方式和喂养方式不同,婴儿12月龄血清HBsAg阳性率无差别(P＞0.05).结论:主被动免疫方法阻断HBV母婴传播效果肯定.HBsAg阳性孕妇所生婴儿12月龄检查HBV-M是必要的.经主被动免疫情况后,HBeAg阳性孕妇自然分娩和母乳喂养没有增加婴儿感染HBV的危险性.     

乙型肝炎病毒宫内感染的传播途径及早期诊断

目的分析羊水、脐带血、母血、胎盘等组织中乙型肝炎病毒标志物(HBV M)及HBV DNA与胎儿感染的关系，探讨HBV母婴传播机制。方法采用微粒子化学发光及核酸扩增杂交梳技术对65例血液乙型肝炎表面抗原(HBsAg)阳性不同孕龄孕妇的羊水、母血、脐带血进行HBV M和HBV DNA检测，对自然流产胎儿或死亡婴儿的胎盘、肝脏、心脏、肺脏进行免疫组织化学检测。结果65例血液HBsAg阳性，不同孕龄孕妇的羊水中HBsAg阳性率为21．50％，脐带血阳性率为20．00％；母血、羊水．脐带血HBsAg、乙型肝炎e抗原(HBeAg)、抗-HBc、HBV DNA均阳性者为6．15％；HBsAg、抗-HBc、抗-HBc阳性、HBV DNA阴性者占13．85％。对4例血液、羊水、脐带血HBsAg、HBeAg、抗-HBc、HBV DNA阳性孕妇分娩或自然流产后胎盘、胎儿及死亡婴儿的肝脏、肺脏、心脏进行免疫组织化学检测发现，胎盘各层组织镜下均可见到HBsAg、HBcAg阳性细胞；在肝脏、肺脏组织中可见到HBsAg、乙型肝炎核心抗原(HBcAg)阳性细胞，心肌组织内未见有HBsAg、HBcAg阳性细胞。结论胎儿感染HBV与羊水、胎盘中的病毒相平行；HBV在宫内可感染胎儿血液、肝脏、肺脏等组织；羊水检测HBV M及HBV DNA可作为胎儿早期HBV感染的诊断依据之一。     

HBsAg阳性母亲所生婴儿联合免疫后乙型肝炎表面抗体的动态变化

目的 通过前瞻性随机对照观察HBsAg阳性母亲所生婴儿接受联合免疫(乙肝免疫球蛋白联合5μg或10 μg重组酵母乙型肝炎疫苗)后乙型肝炎表面抗体(抗-HBs)滴度的动态变化,比较不同剂量乙型肝炎疫苗免疫效果的差异,为更好地建立此类高危人群的免疫策略、监测模式及加强免疫提供基础. 方法 对269例HBsAg阳性母亲的婴儿于出生后12h内进行联合免疫(乙型肝炎免疫球蛋白200 IU,重组酵母乙型肝炎疫苗随机分为5μg和10μg),并在出生时、1、7、12月龄进行HBV DNA载量,HBsAg及抗-HBs滴度的动态监测.根据资料不同运用秩和检验、x2检验及Fisher精确概率法进行统计学分析.结果 (1) HBsAg阳性母亲的婴儿出生后联合免疫一年保护率可达到95.9％.接受不同剂量疫苗免疫婴儿中,HBV感染率没有明显差别(x2=0.876;P=0.377).(2)动态监测未感染婴儿1月龄抗-HBs平均滴度为144.1 mIU/ml,7月龄达最高581.8mIU/ml,12月龄降至397.6 mIU/ml;7月龄抗-HBs滴度小于100 mIU/ml的比例为20.9％,小于10 mIU/ml的比例为7.4％(无/弱应答率); 12月龄抗-HBs滴度小于100 mIU/ml的比例升至30.2％,小于10 mIU/ml的比例则上升至15.9％.(3)7月龄时,10 μg疫苗组婴儿抗-HBs平均滴度高于5μg组(675.3mIU/ml对比425.0 mIU/ml,P=0.001),无/弱应答率显著低于5μg组(2.3％对比12.6％,P=0.002); 12月龄时,l0μg疫苗组婴儿抗-HBs滴度小于100 mIU/ml的比例明显低于5 μg组(20.6％对比40.2％,P=0.001).结论 虽然HBsAg阳性母亲所生婴儿联合免疫1年时的保护率可达95.9％,但仍有30.2％的婴儿此时抗-HBs滴度已降至100 mIU/ml以下,保护性下降,规律监测可有效发现处于无、低应答状态者,及时采取加强免疫措施可防止此类高危人群后期HBV水平传播;联合免疫中,10 μg重组醇母乙型肝炎疫苗在产生抗-HBs滴度水平及降低无、低应答率方面均优于5μg,应将10 μg乙型肝炎疫苗纳入HBsAg阳性母亲所生婴儿的计划免疫.     

HBsAg与抗-HBs同时阳性的慢性乙型肝炎患者临床特点分析

目的分析HBsAg与抗-HBs同时阳性的现象及其临床特点,并探讨其产生的原因。方法收集2011年2月-2014年2月东南大学附属第二医院体检者2260例,其中被诊断为慢性乙型肝炎的患者830例。采用化学发光微粒子免疫分析法筛选HBsAg与抗-HBs同时阳性的患者188例,分为HBeAg阳性组(n=101)和HBeAg阴性组(n=87)。同时选取200例HBsAg阳性、抗-HBs阴性者作为对照,其中HBeAg阳性组80例,HBeAg阴性组120例。检测HBV血清学标志物、肝功能、病毒载量并结合临床进行分析。计数资料组间比较采用χ2检验。结果 HBV血清学标志物在HBsAg与抗-HBs双阳性情况下共有5种模式,其中以HBsAg、抗-HBs、HBeAg及抗-HBc阳性,且抗-HBe阴性多见,占47.9%(90/188),肝功能指标总异常率为69.1%(130/188),HBV DNA总阳性率为56.9%(107/188)。HBeAg阳性的2组HBV DNA均存在高水平复制,其中HBsAg与抗-HBs双阳性组HBV DNA阳性率与对照组比较,差异无统计学意义(χ2=2.632,P0.05);HBeAg阴性组中,HBsAg与抗-HBs双阳性组HBV DNA定量1×105IU/ml的比例与对照组比较,差异有统计学意义(χ2=10.740,P0.05)。对HBV S区进行测序分析发现,测序的80例HBsAg与抗-HBs双阳性患者中有27例患者的HBV S区发生变异,突变率33.7%,且S区变异位点主要有P29L、S61L、P62L、I126T/S、Q129N、M133K、F134L、G145R/K、L175S和L186H等。结论 HBsAg与抗-HBs同时阳性者在乙型肝炎患者中有一定比例,其主要原因可能是病毒株变异所致。这种情况并不代表疾病好转,且抗-HBs出现并不一定能完全有效清除HBsAg,病毒DNA往往存在持续复制,需引起重视。     

替比夫定对乙型肝炎病毒高载量孕妇母婴传播的阻断效果及其安全性

目的 评价妊娠中晚期应用替比夫定阻断HBeAg阳性且高病毒载量孕妇母婴传播的安全性及有效性.方法 选择孕20 ～ 32周,HBeAg阳性、HBV DNA＞ 1.0× 107拷贝/ml孕妇,按患者意愿分替比夫定组和对照组,替比夫定组予替比夫定600 mg/d口服抗病毒治疗直至产后4周或产后继续服用,对照组患者不用抗病毒药物,肝功能异常者使用复方甘草酸苷.两组婴儿产后均接受主、被动联合免疫,出生后12h内、15d注射乙型肝炎免疫球蛋白200 IU及0、1、6个月注射乙型肝炎疫苗20 μg.婴儿7月龄时HBsAg及HBV DNA阳性者为HBV宫内感染. 结果 共纳入220例孕妇,其中替比夫定组120例,对照组100例.替比夫定治疗者均在美国抗逆转录酶药物妊娠登记处注册.分娩前替比夫定组孕妇HBV DNA、HBeAg、ALT水平下降明显.替比夫定组HBV DNA定量于治疗2周迅速下降,之后缓慢下降直至分娩.至分娩前替比夫定抗病毒孕妇有37例HBV DNA定量转阴,转阴率达31％ (37/120),而对照组无一例转阴.随访至7月龄,替比夫定组婴儿HBV宫内感染率为0,显著低于对照组8％ (P=0.002).替比夫定组无一例母儿因不良反应或先天性畸形失访.80例替比夫定治疗者于产后4周停药,随访至产后28周无一例发生严重肝功能损害.两组孕妇产后出血、不良妊娠、剖宫产率及新生儿胎龄、身长、体质量、Apgar评分,差异无统计学意义. 结论 HBeAg阳性、HBV DNA高滴度孕妇妊娠中晚期应用替比夫定抗病毒治疗能明显降低母亲外周血HBV DNA定量,阻断HBV母婴传播,且耐受性和安全性良好.     

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。     

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.     

Hepatitis B virus vaccination and antenatal transmission of HBV markers to neonates

The high prevalence of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) in pregnant women is considered to be the most important factor contributing to the high carrier rate of HBsAg in some populations. Several factors, including the age at which infection occurs, predispose to the acquisition and frequency of the carrier state. The proportion of infected people who become chronic carriers ranges from about 80 to 95% for babies born to HBsAg/HBeAg-positive mothers. In this study of Indonesian infants receiving only active immunization against HBV, we measured the HBV markers passively acquired from their HBsAg-positive mothers. The relationship of these markers with vaccination response and with HBV infection status was studied longitudinally in the infants. In the exposed neonates from the HBsAg-positive mothers (n=61), the seroconversion rate to hepatitis B surface antibody (HBsAb) positivity was 95% after the first booster vaccination, with a geometric mean titre (GMT) of 2017 IUl-1. After 60 months, the GMT in this group decreased to 50 IUl-1. Four newborns in this group became HBsAg carriers. Of the four vaccination failures, three newborns were HBsAg/HBeAg positive at birth, suggesting that they had been infected in utero. No vaccination strategy (active alone, or passive/active) can prevent this transmission from occurring. One carrier was HBsAg negative at birth and up to month 4 but was HBsAg positive at month 12 and subsequently, suggesting a postnatal infection. Vaccination early in life can, to a large extent, prevent perinatal transmission and hepatitis B virus (HBV) infection later in infancy and childhood. In this study, the protective efficacy of the vaccination was 85% in the subcohort of neonates from HBeAg-positive mothers and 100% in the subcohort of neonates from HBeAg-negative mothers. Lack of maternal antibodies to hepatitis B core antigen (HBcAb) correlated strongly with transmission of HBV infection.     

乙型肝炎病毒母婴“零传播”策略分析

目的探讨实现乙型肝炎病毒(HBV)母婴"零传播"的可行性策略。方法回顾性分析2005年1月至2015年12月南京市第二医院进行HBV母婴阻断治疗病例,总结母婴传播的高危因素,采取的有效阻断措施和阻断结果等。结果HBV感染孕妇不论是乙型肝炎表面抗原(+)[HBsAg(+)]、乙型肝炎表e抗原(+)[HBeAg(+)]、乙型肝炎核心抗体(+)[HBcAb(+)]还是HBsAg(+)、乙型肝炎e抗体(+)[HBeAb(+)]、HBcAb(+),只要乙型肝炎病毒脱氧核糖核酸(HBVDNA)<1.0×10^6拷贝/ml,均未发现乙型肝炎母婴传播的病例;HBVDNA≥1.0×10^6拷贝/ml的孕妇,自孕28周左右口服核苷类似物替比夫定或替诺福韦行抗病毒阻断治疗者,亦未发现乙型肝炎母婴传播的病例;HBV母婴传播仅发生在HBVDNA>1.0×10^6拷贝/ml且孕期未进行抗病毒阻断的病例;HBV感染孕妇的婴儿进行乙型肝炎疫苗及乙型肝炎免疫球蛋白(HBIG)联合免疫后,在2月龄、7月龄、12月龄检查乙型肝炎病毒表面抗体,若<100U/ml,给予加强补种一针乙型肝炎疫苗,可达到有效的乙型肝炎疫苗免疫效果。结论HBVDNA载量是乙型肝炎母婴传播的关键预测指标;对于HBV DNA高载量孕妇进行核苷类似物抗病毒治疗有效;正规及时的联合免疫,以及对乙型肝炎疫苗低应答婴儿加强疫苗接种阻断母婴传播;上述3项措施联合进行可以实现HBV母婴"零传播"。     

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。     

HBsAg阳性母亲所生婴儿的母婴阻断及全程接种乙型肝炎疫苗后免疫应答状态

目的 了解HBsAg阳性母亲所生婴儿的母婴阻断及全程接种乙型肝炎疫苗后免疫应答状态及变化规律.方法 对249例HBsAg阳性母亲的新生儿予以联合母婴阻断措施,并全程接种乙型肝炎疫苗,用微粒化学发光法跟踪测定婴儿生后7、12、24、36个月的HBsAg和抗-HBs水平.组间比较采用卡方检验.结果 HBsAg阳性母亲所生婴儿母婴阻断后不同时间免疫应答状态不同,7月龄婴儿无应答率为8.0%(20/249),低应答率为11.7%(29/249),强应答率为80.3%(200/249);12月龄婴儿无应答率为10.8%(13/120),低应答率为26.7%(32/120),强应答率为62.5%(75/120);24月龄婴儿无应答率14.8%(4/27),低应答率为33.3%(9/27),强应答率为51.9%(14/27),36月龄婴儿无应答率为14.3%(1/7),低应答率为28.6%(2/7),强应答率为57.1%(4/7);7月龄组与其他月龄组同等应答状态间比较,差异有统计学意义(x2=21.98,P＜0.01).强应答组婴幼儿抗-HBs效价出生7个月后出现逐渐下降的趋势,效价越高,其下降的例数越少,下降出现的时间越晚.抗-HBs效价＞1000 mIU/mL时,在36个月内下降比率为57.6%(19/33),下降高峰为24个月(57.9%,11/19);抗-HBs效价为100～1000 mIU/mL时,在36个月内下降比率为73.8%(31/42),下降高峰为12个月(54.8%,17/31).HBsAg阳性婴儿7月龄多表现为无应答状态,占全部无应答婴儿的70%(14/20,x2=128.61,P＜0.01),99%(189/191)HBsAg阴性婴儿多为强应答.HBeAg同时阳性母亲的婴儿无应答率有高于HBeAg阴性母亲婴儿的趋势,但差异无统计学意义(9.1%比5.5%,x2=0.24,P＞0.05).结论 HBsAg阳性母亲新生婴儿的母婴阻断及全程接种乙型肝炎疫苗后不同时间免疫应答状态不同,且呈动态变化;无应答状态多见于HBsAg阳性的免疫失败婴儿;HBsAg阴性婴儿大多呈强应答;HBeAg同时阳性的母亲婴儿更易呈低应答.建议完善母婴阻断后管理流程,特别是生后7个月～2年的积极随访监测.     

人乙型肝炎免疫球蛋白定量清除新生儿乙型肝炎病毒表面抗原的研究

目的 根据新生儿出生时HBsAg和HBV DNA的载量,调整人乙型肝炎免疫球蛋白使用量,以期更有效地阻断HBV的母婴传播. 方法 收集出生2h内静脉血HBsAg阳性新生儿资料125例.分为研究组64例,对照组61例,研究组根据新生儿出生时HBsAg感染量调整乙型肝炎免疫球蛋白使用量,与对照组比较新生儿12个月龄以上治疗效果.计量资料采用非正态分布采用秩和检验,计数资料采用x2检验.结果 2组新生儿出生时HBsAg和HBV DNA检测值的差异均无统计学意义(p 值均＞0.05).研究组出生HBV感染新生几64例,12月龄以上成功清除HBsAg者53例,成功清除率为82.8％,感染11例(1.2％).对照组出生HBV感染新生儿61例,12月龄以上成功清除HBsAg者35例,成功清除率为57.4％,感染26例(3.1％).2组出生HBV感染新生儿12个月龄以上清除HBsAg效果比较,x2=9.696,P＜0.05,差异有统计学意义.结论 根据新生儿的HBsAg感染量调整使用乙型肝炎免疫球蛋白,可提高乙型肝炎母婴传播的阻断成功率.     

Combined passive and active immunization for interruption of perinatal transmission of hepatitis B virus in Taiwan

We attempted a clinical trial to interrupt transmission of hepatitis B virus (HBV) infection from hepatitis B surface antigen (HBsAg) positive and hepatitis Be antigen (HBsAg) positive mothers to their infants in Taiwan. Screening of 5,595 pregnant women revealed that 856 (15.3%) were HBsAg positive. Three hundred and sixty-one (42.2%) of the HBsAg positive pregnant women were HBeAg positive. Infants born to HBsAg and HBeAg positive mothers were randomized into 3 groups to receive the HBV vaccine alone or combined with hepatitis B immune globulin (HBIG). HGV vaccine was given at 2, 6, and 10 weeks after birth. Group I received HBV vaccine alone while Group II received HBV vaccine in combination with HBIG at birth and group III received HBV vaccine plus HBIG at birth and again at one month old. Group IV constituted the control group when their parents refused vaccination. At 6 months of age, the HBV carrier rate was 23.7% (9/38) in Group I, 11.1% (4/36) in Group II, and 5.3% (2/38) in Group III infants. Compared with 90% of infants who became HBV carriers in the control group (Group IV), the efficacy of HBV vaccination in preventing HBV infection among these high risk infants at the 6th month was 73.7% in Group I, 87.7% in Group II, and 94.1% in Group III. The antibody to HBsAg (anti-HBs) positivity rate in sera of Group I, II, III infants at 6 months of age was 79.0%, 88.9% and 94.7%, respectively. These initial results indicate that combined passive and active immunization is efficacious in interrupting perinatal transmission of HBV infection.     

Effect of hepatitis B immunoglobulin on interruption of HBV intrauterine infection

AIM: To evaluate the efficacy of hepatitis B immunoglobulin (HBIG) in interrupting hepatitis B virus (HBV) intrauterine infection during late pregnancy.METHODS: We allocated 112 HBsAg positive pregnant women into 2 groups randomly. Fifty seven cases in th HBIG group received 200 IU (unit) HBIG intramuscularly every 4 wk from the 28 wk of gestation to the time of delivery, while 55 cases in the control group received no special treatment. HBsAg, HBeAg, HBcAb, HBeAb, HBsAb and HBV DNA levels were tested in the peripheral blood specimens from all of the mothers at 28 wk of gestation, just before delivery, and in blood from their newborns within 24 h before administration of immune prophylaxis.RESULTS: The intrauterine infection rate in HBIG group and control group were 10.5% and 27.3%, respectively, with significant difference (P&lt;0.05). It showed ascendant trend as HBV DNA levels in the peripheral blood increased before delivery.CONCLUSION: HBIG is potent to cut down HBV intrauterine infection rate significantly when administered to pregnant women regularly during late pregnancy. The possibility of HBV intrauterine infection increases if maternal blood HBV DNA≥10^8 copies/mL.     

HBsAg阳性孕妇免疫接种阻断HBV宫内感染疗效的Meta分析

目的评价HBsAg阳性孕妇产前应用乙肝免疫球蛋白（HBIG）或联用乙肝疫苗阻断胎儿HBV宫内感染的有效性及安全性。方法计算机检索6个数据库,手检9种期刊,并追查参考文献,纳入国内外符合纳入标准的随机对照试验和半随机对照试验,由两名评价员独立筛查文献,评价质量和提取资料。用Revman 4.2.10软件分析数据。采用χ2检验鉴定研究间异质性,使用固定效应或随机效应模型合并结果。结果HBsAg阳性/HBsAg和HBeAg均阳性孕妇孕期应用HBIG总剂量600 IU,胎儿HBV宫内感染率〈空白对照组（RR=0.42,95%CI=0.21-0.83,P=0.01）,新生儿HBV DNA阳性率低于空白对照组（RR=0.30,95%CI=0.10-0.85,P=0.02）,新生儿HBeAg阳性率Anti-HBs阳性率与空白组比较差异无统计学意义;总剂量大于600 IU时,宫内感染率〈空白对照组（RR=0.39,95%CI=0.26-0.58,P〈0.000 01）,新生儿Anti-HBs阳性率与对照组比较差异无统计学意义。HBsAg和HBeAg均阳性孕妇孕期应用HBIG总剂量〉600 IU,胎儿HBV宫内感染率、新生儿HBeAg阳性率、新生儿HBV DNA阳性率、新生儿Anti-HBs阳性率与对照组比较差异均无统计学意义;总剂量600 IU组新生儿HBeAg阳性率和新生儿HBV DNA阳性率与对照组比较差异有统计学意义。结论HBsAg阳性/HBsAg和HBeAg均阳性孕妇孕期应用HBIG可降低胎儿HBV宫内感染率;HBsAg和HBeAg均阳性孕妇孕期应用HBIG阻断宫内感染的疗效尚不清楚。     

Hepatitis B vaccination with or without hepatitis B immunoglobulin at birth to babies born of HBsAg‐positive mothers prevents overt HBV transmission but may not prevent occult HBV infection in babies: a randomized controlled trial

Vertical transmission of Hepatitis B virus HBV can result in a state of chronic HBV infection and its complications. HBV vaccination with or without hepatitis B immunoglobulin (HBIG) prevents transmission of overt infection to the babies. However, whether it also prevents occult HBV infection in babies is not known. Consecutive pregnant women of any gestation found to be HBsAg positive were followed till delivery, and their babies were included in the study. Immediately after delivery, babies were randomized to receive either HBIG or placebo in addition to recombinant HBV vaccine (at 0, 6, 10 and 14 weeks). The primary end‐point of the study, assessed at 18 weeks of age, was remaining free of any HBV infection (either overt or occult) plus the development of adequate immune response to vaccine. The babies were further followed up for a median of 2 years of age to determine their eventual outcome. Risk factors for HBV transmission and for poor immune response in babies were studied. Of the 283 eligible babies, 259 were included in the trial and randomized to receive either HBIG (n = 128) or placebo (n = 131) in addition to recombinant HBV vaccine. Of the 222 of 259 (86%) babies who completed 18 weeks of follow‐up, only 62/222 (28%) reached primary end‐point. Of the remaining, 6/222 (3%) developed overt HBV infection, 142/222 (64%) developed occult HBV infection, and 12/222 (5%) had no HBV infection but had poor immune response. All 6 overt infections occurred in the placebo group (P = 0.030), while occult HBV infections were more common in the HBIG group (76/106 [72%] vs. 66/116 [57%]; P = 0.025). This may be due to the immune pressure of HBIG. There was no significant difference between the two groups in frequency of babies developing poor immune response or those achieving primary end‐point. The final outcome of these babies at 24 months of age was as follows: overt HBV infection 4%, occult HBV infection 42%, no HBV infection but poor immune response 8% and no HBV infection with good immune response 28%. Women who were anti‐HBe positive were a low‐risk group, and their babies were most likely to remain free of HBV infection (occult or overt) and had good immune response to the vaccine. Maternal HBeAg‐positive status and negativity for anti‐HBe predicted not only overt but also any infection (both overt and occult) in babies. In addition, high maternal HBV DNA and treatment with vaccine alone were significant factors for overt HBV infection in babies. The current practice of administration of vaccine with HBIG at birth to babies born of HBsAg‐positive mothers is not effective in preventing occult HBV infection in babies, which may be up to 40%. Because the most important risk factors for mother‐to‐baby transmission of HBV infection are the replicative status and high HBV DNA level in mothers; it will be worthwhile investigating the role of antivirals and HBIG administration during pregnancy to prevent mother‐to‐child transmission of HBV infection.