HBIG联合乙肝疫苗阻断HBV母婴传播随访5年效果评价

目的观察HBIG联合乙肝疫苗免疫阻断HBV母婴传播随访5年的防治效果。方法将204例HBsAg及HBeAg双阳性孕妇及所生的新生儿按不同阻断方法随机分为2组。观察组106例,于孕28、32、36周肌肉注射高效价乙肝免疫球蛋白（HBIG）共3次;对照组98例,常规随访检查,未注射药物。两组的新生儿、婴儿于12个月、24个月及幼儿于36个月、60个月龄采血检测HBsAg及抗-HBs。结果孕晚期预防性应用HBIG被动免疫组孕妇所产新生儿的HBsAg阳性率显著低于对照组（x^2=8．45,P〈0．05）;抗-HBs阳性率显著高于对照组（x^2=-19．52,P〈0．001）。随访5年后,两组幼儿的HBsAg、抗-HBs阳性率差异均有统计学意义（分别为P〈0．001和P〈0．05）。结论HBIG联合乙肝疫苗免疫可有效阻断乙肝病毒母婴传播,减少婴幼儿HBV感染率。     

孕妇HBIG被动免疫阻断HBV母婴垂直传播的临床研究

目的 :研究HBV阳性孕妇孕期应用高效价乙肝免疫球蛋白HBIG预防HBV宫内感染的作用机理。方法 :将 1 0 0例乙肝表面抗原HBsAg阳性孕妇随机分为两组 ,预防组 6 0例 ,于孕 2 8、32、36周肌肉注射HBIG三次 ,每次2 0 0IU ;对照组 4 0例 ,只随访查体不用药。两组孕妇所生婴儿均于出生后 2 4小时内肌肉注射HBIG 1 0 0IU一次 ,注射乙肝疫苗时间和剂量均按正常婴儿的操作方案进行。母儿血清HBsAg ,HBeAg和抗 -HBs用固相放免法检测 ,HBV -DNA用荧光定量PCR检测。结果 :HBIG预防组孕妇的婴儿HBV感染率显著低于对照组 (P <0 .0 5 ) ;预防组婴儿血清抗 -HBs检出率显著高于对照组 (P <0 .0 0 1 ) ;HBV -DNA含量显著低于对照组 (P <0 .0 5 )。结论 :孕妇于孕期多次注射HBIG进行被动免疫可有效地阻断乙型肝炎病毒母婴传播 ,减少婴儿HBV感染率     

国产乙型肝炎疫苗和HBIG联合阻断乙型肝炎母婴传播效果研究

本文采用乙型肝炎疫苗和HBIG,经3种不同的联合免疫方案,对阻断乙型肝炎母婴传播的效果进行了研究。结果证明,3个组联合免疫后12个月的抗-HBs阳转率为75%～90%;抗-HBs平均浓度(mIU/ml)为32.55～42.93;阻断率为80.00%～93.3%。联合免疫的效果是满意的。     

HBIG阻断乙型肝炎病毒母婴传播

目的:评价HBsAg阳性母亲孕晚期肌注HBIG(乙肝免疫球蛋白)及婴儿出生后HBIG联合乙肝疫苗对HBV母婴传播及慢性化阻断的效果. 方法:历史对照组只对婴儿进行乙肝疫苗的全程免疫;HBIG组母亲孕晚期3 mo每月肌注200 u的HBIG;婴儿出生时、半月龄时分别肌注200 u的HBIG,并常规接种乙肝疫苗. 随访两组婴儿HBsAg变化情况,采用历史对照临床试验评价母亲及新生儿注射HBIG对HBV母婴传播及慢性化的阻断效果. 结果:历史对照组HBV宫内感染率5.34%,随访时婴儿HBsAg转阳率5.15%,HBV感染慢性化率87.5%;HBIG组分别为5.26%,0,18.18%. 经统计学检验,两组HBV宫内感染率无显著差异(P=1.000),但婴儿HBsAg转阳率及HBV感染慢性化率具有显著差异(P分别为0.019, 0.001). 结论:母亲孕晚期注射HBIG对阻断HBV宫内传播效果不明显;母亲及新生儿注射HBIG可显著提高乙肝疫苗对婴儿出生后HBsAg阳转及HBV感染慢性化的阻断效果.     

拉米夫定阻断乙型肝炎病毒母婴传播的疗效观察

目的:评价妊娠中期应用拉米夫定对乙型肝炎病毒(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52例孕妇于孕20~26周开始服用拉米夫定100mg/d至分娩后,乙型肝炎免疫球蛋白(HBIG)组61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HBVDNA、HBsAg和抗-HBs定量变化。数据行t检验和χ2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34.6%,肝功能异常者全部恢复正常。该组52例新生儿随访至1月龄时HBsAg或HBV DNA均为阴性,宫内感染率为0,与HBIG组宫内感染率(14.8%)相比,差异有统计学意义(χ2=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9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水平较高的孕妇,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,且用药安全,未见明显不良反应。     

Elimination of hepatitis B virus infection in children: experience and challenge in China

Chronic hepatitis B virus (HBV) infection is a serious health issue because of its severe sequelae. Prevention of mother-to-child transmission (MTCT) of HBV is critical to eliminate chronic HBV infection. Here, we reviewed the progress toward the elimination of HBV infection in children in China in the recent decade. A universal hepatitis B vaccination program started from 2002 has been intensified, with the coverage of timely birth dose >95% of all newborn infants from 2012. Since 2011, China has taken a nationwide program to administer hepatitis B immunoglobulin (HBIG) with free of charge in all neonates of HBV-infected mothers, leading to a significant increment of timely use of HBIG. The prevalence of hepatitis B surface antigen (HBsAg) was declined from around 10% among children in 1980s to <0.5% among children born after 2011. Administration of oral antiviral agents in HBV-infected pregnant women with HBV DNA >2 × 10⁵ U/mL during the third trimester is increasing, which will further reduce MTCT of HBV. However, there are some challenges in the elimination of HBV infection in children, which need to overcome by the concerted efforts. Nevertheless, it is anticipated that China will achieve the goal set by the World Health Organization that the prevalence of HBsAg in children aged <5 years is ≤0.1% by 2030.     

联合应用HBIG与乙肝疫苗阻断乙型肝炎病毒母婴传播

成都地区6305例孕妇HBsAg阳性率为3.60％(227/6305)。HBsAg阳性者中HBeAg阳性率为40.97％(93/227)。联合应用HBIG和乙肝疫苗对HBsAg、HBeAg均阳性母亲所生的49例婴儿作预防注射,12个月后,受试者抗-HBs阳性率为76.67％(23/30),18个月后,抗-HBs阳性率为95.45％(21/22),HBsAg均为阴性(0/49)。63例婴儿单用HBIG,12个月后,HBsAg和抗-HBs阳性率分别为5.88％(2/34)和85.29％(29/34),而对照组观察12个月后HBsAg阳性率为60％(15/25),说明用HBIG和乙肝疫苗联合阻断HBV母婴传播效果良好,值得推广应用。     

乙肝免疫球蛋白阻断病毒母婴传播的效果观察

目的 :探讨高效价乙肝免疫球蛋白 (HBIG)阻断乙型肝炎病毒 (HBV)母婴传播的作用机理。方法 :将5 0例HBsAg阳性的孕妇随机分成两组 ,实验组 30例 ,分别自孕 2 8周、32周、及 36周肌肉注射HBIG2 0 0IU ,分娩后 2 4h内再注射HBIG 2 0 0IU 1次 ;对照组 2 0例 ,不用HBIG。两组孕妇所生婴儿均于出生后 2 4h内肌肉注射HBIG 10 0IU 1次 ,注射乙肝疫苗的时间和剂量均按正常婴儿的操作方案进行。母儿血清HBsAg ,HBeAg和抗 HBs用固相放免法检测 ,HBV DNA用荧光定量PCR检测。结果 :实验组婴儿血清HBsAg和HBV DNA检出率明显低于对照组 (P <0 .0 5 ) ;实验组婴儿抗 HBs阳性率显著高于对照组 (P <0 .0 5 )。结论 :孕妇于孕期多次注射HBIG进行被动免疫 ,可有效地阻断乙型肝炎病毒母婴传播 ,减少婴儿HBV感染率。     

不同方法阻断乙型肝炎病毒母婴垂直传播的临床观察

目的 探讨阻断乙型肝炎病毒母婴垂直传播的方法。方法 将94例HBsAg阳性孕妇分成4组,单纯HBVac治疗组29例,单纯HBIG治疗组19例,左旋咪唑涂布剂加两者联合应用13例,未治疗组33例,均在孕26周起开始注射,孕妇和新生儿血清HBsAg,抗－HBs,HBeAg,抗－HBe,抗－HBc检测采用ELISA法。94例孕妇按分娩方式不同分别观察对乙肝病毒母婴传播的影响。结果 脐血中HBsAg阳性率,HBVac治疗组为17．24％,HBIG治疗组为5．26％,联合治疗组为0,未治疗组为21．21％。在不同的分娩方式中,急症剖宫产新生儿脐血HBsAg阳性率为0,行择期剖宫产者为10．5％,经阴道分娩者为16．9％。结论 携带HBV孕妇于孕晚期给予HBVac,HBIG和左旋咪唑涂布剂联合两者治疗后,可有效阻断HBV母婴之间传播,以联合治疗组效果最佳,剖宫产术有助于阻断HBV母婴传播。     

孕妇主、被动联合免疫阻断乙肝母婴传播的研究

目的:探讨乙型肝炎母婴垂直传播阻断的影响因素和免疫效果。方法:51例HBV感染但无临床症状的孕妇分成三组,试验组Ⅰ:孕妇为HBAg单阳性,产期及新生儿均注射过HBIG;试验组Ⅱ:孕妇为HBsAg、HBeAg双阳性,产前及新生儿均注射过HBIG;对照组;孕妇为HBsAg单阳性或HBsAg、HBeAg双阳性,产前及新生儿均未注射过HBIG;上述所有新生儿均注射过乙肝疫苗。随访三年,每年检测新生儿HBeAg和抗---HBs。结果:实验组(Ⅰ+Ⅱ)总的HBsAg携带率从5.00%降为2.50%,对照组的HBsAg携带率为0%。对照组抗-HBs阳性率、滴度下降更明显(p<0.05)。结论:联合免疫以及单纯乙肝疫苗免疫对阻断乙肝母婴传播的效果都是确定的,联合免疫对维持乙肝疫苗持久效果更佳,应重视对乙肝高危新生儿的监测和随访。     

孕晚期注射乙型肝炎免疫球蛋白阻断乙型肝炎病毒母婴传播的临床观察

目的：探讨HBsAg阳性和HBeAg阳性携带孕妇孕晚期应用乙型肝炎免疫球蛋白（HBIG）阻断乙型肝炎病毒（HBV）母婴传播的效果。方法：将孕妇分为双阳性组（A组）和单阳性组（B组）[HBsAg（＋）及HBeAg（＋）称为“双阳性”（A组）,HBsAg（＋）及HBeAg（-）称为“单阳性”（B组）];新生儿分为HBIG组和非HBIG组（对照组）;HBIG组孕妇孕28、32、36周各注射HBIG200IU（共3次,部分仅注射1～2次）,非HBIG组仅常规产检及监护;对两组新生儿0、6个月的静脉血作乙型肝炎两对半检测。结果：①A组孕妇的外周血HBV-DNA阳性率（76.92%）显著高于B组孕妇（8.55%）,P〈0.01;②A组孕妇所生HBIG组新生儿出生24h的HBsAg阳性率（10.64%）显著低于非HBIG组（33.33%）,P〈0.05;③A组孕妇所生HBIG组6月龄新生儿HBsAb阳转率（78.72%）明显高于非HBIG组（38.39%）,P〈0.01;B组孕妇所生HBIG组6月龄新生儿HBsAb阳转率（80.65%）高于非HBIG组（64.41%）,P〈0.05。结论：双阳性孕妇孕晚期应用HBIG可有效降低乙型肝炎宫内感染率;无论是双阳性还是单阳性孕妇,孕晚期应用HBIG可提高6月龄新生儿HBsAb阳转率。     

A randomized control trial on interruption of HBV transmission in uterus

Objective To study the interruptive effect of hepatitis B virus (HBV) specific immunolobulin (HBIG) before delivery in attempt to prevent intrauterine transmission of HBV.Methods Nine hundred and eighty HBsAg carrier pregnant women were randomly divided into HBIG group and control group. Each subject in the HBIG group received 200 IU or 400 IU of HBIG intramuscularly at 3, 2 and 1 month before delivery. The subjects in the control group did not receive any specific treatment. All newborn infants received 100 IU of HBIG intramascularty after venous blood samples were taken at birth and 2 weeks after birth, followed by 30 μg plasma-derived HB vaccine or 5 μg recombinant yeast-derived hepatitis B vaccine at 1, 2 and 7 months of age. Blood tests were performed for all the lying-in women and their neonates. Blood specimens were tested for HBsAg and HBeAg by enzyme immunoassay. All infants were followed up for 1 year.Results In the HBIG group, 491 neonates were born to 487 HBV carrier mothers; and in the control group, 496 neonates were born to 493 HBV carrier mothers. The rates of intrauterine transmission in the two groups were 14.3% and 5.7% respectively (χ2=20.280, P&lt;0.001), and the rates of chronic hepatitis B in the two groups were 2.2% and 7.3% respectively (χ2=13.696, P&lt;0.001). The high risk factors of intrauterine HBV infection included HBsAg HBeAg double positive and HBV DNA positive in the peripheral blood of pregnant women.Conclusion HBV infection in the uterus may be interrupted by injecting multiple intramuscular HBIG injections before delivery without causing any side-effects.     

Prevention of intrauterine infection by hepatitis B virus with hepatitis B immune globulin: efficacy and mechanism

Objective　To evaluate the efficacy of hepatitis B immune globulin (HBIG) in preventing intrauterine infection by hepatitis B virus (HBV) and to investigate its mechanism. Methods　Forty-eight pregnant women positive for hepatitis B surface antigen (HBsAg) were randomly divided into 2 groups. The 34 women in the study group were injected with HBIG during pregnancy; the other 14 women were controls. Maternal blood samples were taken before HBIG injection and at delivery. Neonatal blood samples were taken within 24 hours after birth before HBIG and hepatitis B vaccine were given. HBsAg and antibody to HBsAg (anti-HBs) were tested by radioimmunoassay. Results　None of the 35 newborns (including 2 twins) in the study group was positive for HBsAg, but 3 (21%) in the control group were positive (P=0.02). The HBsAg titers in the women in the study group decreased after HBIG injection. Of the 35 newborns in the study group, 32 (91%) were positive for anti-HBs. Conclusion　Systematic injections of HBIG during pregnancy may prevent intrauterine HBV infection, the mechanism of which may be reduction of maternal HBV viremia and production of fetal passive immunity.     

福建省泉州市HBsAg阳性产妇所生新生儿免疫失败流行特征

目的 了解泉州市HBsAg阳性产妇所生儿童的乙肝免疫状况,评价本市乙肝母婴阻断方案的保护效果,并分析免疫失败的流行特征。方法 通过问卷调查,收集整理泉州市惠安、石狮两县HBsAg阳性产妇及其新生儿基本信息,在新生儿完成3针乙肝疫苗接种后1~2月,采集血标本并通过胶体金法检测HBsAg、抗HBs。结果 HBsAg阳性产妇所生儿童经乙肝疫苗和乙肝免疫球蛋白（HBIG）联合免疫后,其抗-HBs阳性率为93.1%,HBsAg阳性率为1.8%,免疫失败率为6.9%。新生儿乙肝免疫失败与HBsAg阳性产妇谷丙转氨酶（ALT）值和HBV-DNA值高低、产妇HBeAg阳性与否有关（P<0.05）,ALT、HBV-DNA值越高,免疫失败的概率越大,HBeAg阳性产妇所生新生儿免疫失败率高于HBeAg阴性;乙肝母婴阻断与HBsAg阳性产妇ALT值和HBV-DNA值高低有关（P<0.05）,ALT、HBV-DNA值越高,母婴阻断失败的概率越大。HBV-DNA≥10⁴ cps/mL HBsAg阳性产妇选择20 μg/mL乙肝疫苗和200 IU HBIG进行接种的率明显高于HBV-DNA<10⁴ cps/mL 产妇。结论 泉州市现行乙肝母婴阻断策略实施效果较好,建议HBeAg阳性且HBV DNA载量>6 log10 IU/mL的母亲在孕期进行干预治疗,以进一步减少免疫失败率,提高母婴阻断率。     

A pilot study on the combined therapy of granulocyte-macrophage colony-stimulating factor and hepatitis B vaccine on chronic hepatitis B virus carrier children

Objective To observe the efficacy of treating intrauterine infected chronic hepatitis B virus (HBV) carrier children with a combination of granulocyte-macrophage colony-stimulating factor (GM-CSF) or hepatitis B immunoglobulin (HBIG) plus recombinant hepatitis B vaccine (rHBvac).Methods A total of 27 chronic HBV infected children, who were born to HBV carrier mothers and received hepatitis B immunoprophylaxis at birth, were randomized into 2 groups: one receiving a combined therapy of 50 μg of GM-CSF plus 10 μg of rHBvac injected intramuscularly at the same location (GM-CSF group, 14 children) or 200 IU HBIG and 10 μg rHBvac in different muscles (HBIG group, 13 children) on a monthly four-dose schedule. HBV-DNA quantification and other HBV serological markers were tested before and after the four-dose therapy. Results Twelve children in each group completed the study. Of them, 3 children in the GM-CSF group and 4 in the HBIG group had elevated serum alanine transaminase (ALT) before the trial, and then 2 in each group became ALT normal after the treatment. Before the therapy, hepatitis B e antigen (HBeAg) positivity was found in nine children in the GM-CSF group and 10 in the HBIG group. One from each group had an HBeAg/anti-HBe seroconversion after the treatment. The quantity of HBV-DNA was significantly lower after the treatment (P=0.023) in GM-CSF group, but was not significantly reduced in HBIG group. No subjects were found to be negative for hepatitis B surface antigen (HBsAg) after the treatment, and no serious adverse events occurred in either group. Conclusion Combined GM-CSF and rHBvac therapy inhibit HBV replication in carrier children who were not protected after treatment with immunoprophylaxis.     

HBIG联合乙肝疫苗阻断HBV母婴传播的效果研究

目的 观察HBIG联合乙肝疫苗阻断HBV母婴传播的临床效果.方法 将138名HBsAg、HBeAg双阳性的母亲及所生的新生儿按不同的阻断方法随机分为3组,在新生儿及婴儿12个月龄时,采血清检测HBsAg和抗-HBs,并对结果进行统计分析.结果 研究Ⅱ组和对照组新生儿HBsAg阳性率分别为2.22%和26.53%,差异具有显著性（P＜0.005）;研究Ⅱ组和对照组新生儿抗-HBs阳转率分别为31.11%和8.16%,差异有显著性（P＜0.005）;研究Ⅰ组、研究Ⅱ组和对照组的12月龄婴儿HBsAg阳性率分别为6.82%、2.22%和26.53%,差异有统计学意义（P＜0.005）;研究Ⅰ组、研究Ⅱ组和对照组的12月龄婴儿抗-HBs阳转率分别为79.55%、73.33%和65.31%,差异无统计学意义（P＞0.05）.结论 乙肝免疫球蛋白与乙肝疫苗联合免疫阻断母婴垂直传播的效果优于单独接种乙肝疫苗.     

核苷类抗病毒药物阻断乙肝病毒母婴传播的研究进展

核苷类抗病毒药物能降低孕妇血中乙肝病毒载量,核苷类抗病毒药物联合新生儿接种乙肝免疫球蛋白(HBIG)、乙肝疫苗,阻断乙肝病毒母婴传播效果比新生儿单纯接种HBIG、乙肝疫苗的效果更好。孕妇和胎儿安全性等问题尚需深入研究。慢性乙型肝炎和携带病毒的孕妇可以考虑服用核苷类抗病毒药物,提高阻断乙肝病毒母婴传播的效果。     

拉米夫定抗病毒治疗阻断HBV母婴垂直传播的临床研究

目的 观察乙肝表面抗原（HBsAg）阳性母亲产前应用拉米夫定（LAM）、乙肝免疫球蛋白（HBIG）及婴儿乙肝疫苗（Vaccine）阻断乙型肝炎（HBV）母婴垂直传播的疗效和安全性.方法 2008年12月-2011年1月在我院产科住院分娩的慢性HBV感染孕妇76例,治疗组47例,孕28周口服拉米夫定进行抗病毒治疗,对照组29例不进行抗病毒治疗.结果 治疗组47例孕妇所产婴儿出生时HBsAg（＋）并HBV-DNA（＋） 1例（2.1%）,HBsAb（＋）39例（83.0%）,感染率为2.1%;对照组29例孕妇所生婴儿出生时HBsAg（＋）3例（10.3%）,HBV-DNA（＋）8例（27.6%）,HBsAb（＋）17例（58.6%）,感染率27.6%.两组妇女所生婴儿HBV感染率相比差异有统计学意义（P＜0.05）.结论 孕晚期LAM抗病毒治疗用于预防HBV母婴传播有确切效果和近期安全性,值得临床进一步探讨.     

乙肝疫苗和乙肝免疫球蛋白联合应用阻断乙肝母婴传播的Meta分析

目的：对乙肝疫苗（HBVac）和乙肝免疫球蛋白（HBIG）联合应用阻断乙肝母婴传播的效果进行合并定量分析。方法：采用固定效应模型,对符合纳入标准的9项随机对照试验进行Meta分析。结果：9项独立研究的OR值波动在0．11～1．12,各试验结果缺乏一致性。Meta分析的OR值为0．46,95％可信区间为0．32～0．67。结论：在综合了9项研究的信息后,提示乙肝疫苗和乙肝免疫球蛋白联合组的效果优于单用乙肝疫苗组。     

乙型肝炎病毒宫内传播的分子生物学证据

采用病毒DNA分子杂交,Southern吸印及PAP等技术,从引产死婴心血及肝组织中发现HBV-DNA及HBsAg,从而为乙型肝炎病毒宫内传播提供了分子生物学证据。本研究还表明HBV宫内传播频率较低,为HBV母婴传播的产后立即特异性免疫预防提供了实践依据。