常规免疫预防阻断HBeAg阴性HBV感染母婴传播的效果及影响因素

目的探讨常规免疫预防措施在阻断HBeAg阴性HBV感染母婴传播的效果及影响因素。方法选取我院在2010年12月至2013年12月期间收治、符合纳入标准的HBeAg阴性乙型肝炎孕妇250例及其新生儿272例,并进行随访。记录新生儿乙型肝炎疫苗接种情况、采血检测HBsAg和抗-HBs阳性情况及喂养方式等,并记录孕妇分娩方式及乙型肝炎免疫球蛋白(Hepatitis B immune globulin,HBIG)注射情况等。结果所有新生儿均接种乙型肝炎免疫球蛋白和乙型肝炎疫苗。新生儿均采集脐带血,其中脐带血显示有44例HBsAg呈阳性,但随访中,对272例儿童采血检测HBsAg和抗-HBc,均呈阴性,其中有210例儿童抗-HBs呈阳性;孕妇分娩方式对其出生子女抗-HBs差异无统计学意义(χ~2=0.016,P=0.901);孕期是否接种乙型肝炎免疫球蛋白对提高新生儿应答乙型肝炎疫苗作用无明显效用(χ~2=0.474,P=0.491);随访期间,母乳喂养、人工喂养及混合喂养的新生儿分别为148例、83例、41例,3种喂养方式的新生儿抗-HBs差异无统计学意义(χ~2=5.959,P=0.051)。结论新生儿进行常规免疫预防后,可以阻断HBeAg阴性HBV感染母婴传播;新生儿的喂养方式、分娩方式、母体注射乙型肝炎免疫球蛋白等对儿童乙型肝炎抗体应答情况均无明显影响。     

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.     

胎盘HBsAg与新生儿乙型肝炎病毒血清学标志物的关系

目的 探讨HBsAg阳性孕妇胎盘HBsAg与新生儿HBV血清学标志物和HBVDNA的关系.方法 免疫组织化学亲和素-生物素复合物(ABC)法检测155例HBsAg阳性孕妇的胎盘HBsAg,ELISA法检测新生儿HBV血清学标志物,荧光定量PCR法检测新生儿血清HBVDNA.各指标阳性率的比较采用x2检验.结果 155例孕妇的胎盘各型细胞均存在不同程度的HBsAg阳性表达,总的胎盘HBsAg阳性58份,阳性率为37.4％;蜕膜细胞、滋养层细胞、绒毛间质细胞和绒毛毛细血管内皮细胞HBsAg阳性各有58、40、29和11份,阳性率分别为37.4％、25.8％、18.7％和7.1％;胎盘从母体面的蜕膜细胞至胎儿面的绒毛毛细血管内皮细胞HBsAg阳性率逐渐下降(趋势x2=43.01,P=0.00).胎盘HBsAg阳性与新生儿HBsAg、HBeAg阳性均有关(x2=4.88,P＜0.05;x2 =3.86,P＜0.05),而与新生儿抗-HBe、抗-HBc无关(x2=3.36,P＞0.05;x2=0.00,P＞0.05).胎儿面的绒毛毛细血管内皮细胞和绒毛间质细胞HBsAg阳性时,新生儿HBsAg阳性的危险性高(OR=5.31,95 ％CI:1.38～20.40;OR=3.33,95％CI:1.16～9.52);而滋养层细胞和绒毛间质细胞HBsAg阳性时,新生儿HBeAg阳性的危险性较大(OR=3.04,95％ CI:1.45～6.39;OR=3.05,95％CI:1.32～7.03);胎盘HBsAg阳性与新生儿HBV DNA阳性无关(x2=0.09,P＞0.05).结论 越接近胎儿面的胎盘细胞HBsAg表达阳性,新生儿HBV血清学标志物阳性的危险性越大.HBsAg在胎盘中以“逐层转移”的方式进入胎儿血循环.     

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.     

肝病患者血清中HBVcccDNA检测的临床意义

目的 了解cccDNA与病毒复制及拉米夫定耐药突变(YMDD)及肝脏病变的关系.方法 采用分子信标PCR技术检测HBV携带者、慢性乙型肝炎、乙型肝炎肝硬化、肝癌患者血清中cccDNA与HBVDNA及YMDD突变.结果 对283例不同HBV感染者血清进行了cccDNA检测,阳性123例(43.46%),全部为HBVDNA阳性标本;cccDNA与血清HBV-DNA相关(x2=28.27,P＜0.01)及ALT相关(x2=48.46,P＜0.01).68例接受拉米夫定治疗半年以上患者复查血清ALT、HBVDNA、YMDD及ccDNA,显示ALT异常32例(与cccDNA相关x2=48.46,P＜0.01),HBVDNA阳性24例(与cccDNA相关x2=28.27,P＜0.01),其中包括YMDD阳性18例与cccDNA阳性16例(P=0.046).结论 血清cccDNA,是反映HBV复制及肝脏细胞损伤的血清标志.监测YMDD与血清cccDNA可以提示抗病毒治疗中HBV复制状态及病变进展情况.     

HBsAg及HBV DNA定量水平在慢性乙型肝炎、肝硬化和肝癌患者中的变化

目的 了解HBsAg定量水平在慢性乙型肝炎、乙型肝炎肝硬化、HBsAg阳性的原发性肝癌患者中的变化及其在3组患者中与HBV DNA的相关性. 方法 采集47例慢性乙型肝炎患者(乙型肝炎组),72例乙型肝炎肝硬化患者(肝硬化组)及54例肝癌患者(肝癌组)的血清标本,用雅培化学发光法进行HBsAg定量测定,荧光PCR定量法检测HBV DNA量水平.多组分析采用Kruskal-Wallis检验,两组间比较采用Mann-WhitneyU检验,相关性分析采用Spearman检验.结果 HBsAg定量值在乙型肝炎、肝硬化、肝癌组患者中的中位数分别为2361.10、1001.64、594.35IU/ml,3组间呈逐渐下降趋势,x2= 24.394,P＜0.05,差异有统计学意义;乙型肝炎组与肝硬化组比较,Z= -3.754,P＜0.05,差异有统计学意义;乙型肝炎组与肝癌组比较,Z=-4.630,P＜0.05,差异有统计学意义;而肝硬化组与肝癌组比较,差异无统计学意义.HBeAg阳性患者,HBsAg定量值在乙型肝炎组、肝硬化组、肝癌组患者的中位数分别为3259.83、1077.30、789.72 IU/ml,3组间呈下降趋势,x2= 15.643,P＜0.01,差异有统计学意义.对于HBeAg阴性患者,HBsAg定量值在乙型肝炎组、肝硬化组、肝癌组患者的中位数分别为1669.00、1001.64、582.05 IU/ml,3组间呈下降趋势,x2 =6.423,P＜0.05,差异有统计学意义.HBV DNA定量值在乙型肝炎组、肝硬化组、肝癌组患者的中位数分别为5.3579、 4.2207、1.0000 log10拷贝/ml,4分位数间距分别为(4.3579 ～6.8745)、(0.0000 ～ 5.7393)、(0.0000 ～ 4.6651)log10拷贝/ml,3组HBV DNA定量值比较,x2=31.412,P＜0.05,差异有统计学意义; HBsAg与HBV DNA在乙型肝炎组(r= 0.297,P＜0.05)、肝硬化组(r= 0.346,P＜0.05)、肝癌组(r=0.452,P＜0.05)均呈正相关.结论 HBsAg定量值在慢性乙型肝炎、肝硬化、肝癌患者中逐渐降低,且与HBV DNA水平正相关.     

505名医务人员接种甲型H1N1流行性感冒疫苗3个月内的免疫效果分析

目的 了解内蒙古大兴安岭地区医务人员接种甲型H1N1流行性感冒(流感)疫苗的免疫效果.方法 采用单纯随机抽样方法,通过ELISA法对505名接种和129名未接种H1N1流感疫苗的健康医务人员半定量测定血清H1N1流感IgG.按年龄、性别、职业和从接种到不同采样时间检测结果进行分组分析.率的比较行x2检验.结果 505名医务人员接种甲型H1N1流感疫苗后,401人特异性抗体阳性,占79.4%;弱阳性50人,占9.9%.129名未接种组中特异性抗体阳性59人,占45.7%;弱阳性15人,占11.6%.两组各年龄分层比较差异无统计学意义(P＞0.05).接种组男性抗体阳转率为95.7%,女性为87.4%(x2=6.40,P＜0.05);未接种组男性抗体阳转率为73.3%,女性为52.5%(x2=4.07,P＜0.05).接种组护士和医生的阳转率分别为86.0%和94.5%(x2=9.16,P＜0.01),未接种组分别为43.8%和75.0%(x2=12.61,P＜0.01).从接种到不同采样时间特异性抗体检测结果比较,接种第80～89天阳转率为81.5%,与接种第30～39、50～59、60～69天的阳转率分别为100.0%、94.7%和93.6%比较,差异有统计学意义(x2=3.96,P＜0.05;x2=7.15,P＜0.01;x2=9.98,P＜0.01).结论 内蒙古大兴安岭地区医务人员甲型H1N1流感疫苗接种有良好免疫效果.免疫后第80～89天免疫水平较前有显著下降.

Abstract：

Objective To investigate the immunization effect of influenza A/H1N1 vaccine in health care workers (HCW) in Inner Mongolia Greater Khingan Mountains area. Methods Five hundred and five HCW who received A/H1N1 influenza vaccination (immunized group) and 129 staffs who didn't receive the vaccination (unimmunized group) were randomly sampled for semiquantitative testing of serum H1N1 antibody (IgG) levels by enzyme-linked immunosorbent assay (ELISA).Results were analyzed and stratified by age, sex, occupation and the time interval between the time of vaccination and serum sample collection. The antibody positive rates of the two groups were compared by x2test. Results There were 401 (79. 4%) HCW whose H1N1 antibody were positive and 50 (9.9%) whose antibody were weak positive among 505 immunized HCW. While among 129 unimmunized HCW, there were 59 (45.7%) whose antibody were positive and 15 (11.6%) whose antibody were weak positive. The seroconversion rates of specific antibody were not significantly different among the different age groups after receiving A/H1N1 influenza vaccine (P＞ 0.05).However, there were statistical differences of the seroconversion rates among different sex groups (men 95.7% vs women 87.4% in immunized group, x2=6.40, P＜0.05; and men 73.3% vs women 52.5% in unimmunized group, x2 =4.07, P＜0.05) and different occupation groups (doctor 86.0% vs nurse 94.5% in immunized group, x2 = 9. 16, P＜0.01; and doctor 43. 8% vs nurse 75.0% in unimmunized group, x2=12.61, P＜0.01 ). The seroconversion rate was 81.5% after 80 to 89 days of vaccination, which was significantly lower than those after 30 to 39, 50 to 59 days and 60 to 69 days of vaccination, which was 100.0%, 94.7% and 93.6%, respectively (x2 =3.96, P ＜0.05; x2=7.15, P ＜0. 01; x2 = 9. 98, P＜0. 01). Conclusions A/H1N1 influenza vaccination can induce effective immune response in HCW in Greater Khingan Mountains area of Inner Mongolia. However,the level of specific antibody significantly reduces after 80 to 89 days of vaccination.     

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,HCV-Ag和AFP在肝硬变和肝细胞癌组织中的表达

目的探讨HBsAg,HCV-Ag和AFP在抗肝癌免疫应答中的意义.方法用免疫组织化学APA法检测HBsAg,HCV-Ag和AFP在肝硬变和肝细胞癌中的表达、定位和分布.结果在LC组织中,HBsAg为53.3%(16/30),HCV-Ag为63.3%(19/30),AFP为26.7%(8/30);在HCC组织中,HBsAg为17.5%(7/40),HCV-Ag为52.5%(21/40),AFP为45.0%(18/40);在癌周围组织(PCT)中,HBsAg为65.6%(21/32),HCV-Ag为50.0%(16/32),AFP为3.1%(1/32);统计学处理显示,在HCC组织中,HBsAg阳性率显著低于LC(x2=9.977,P＜0.01)和PCT(x3=17.325,P＜0.01);HCV-Ag阳性率与LC和PCT无显著差异;AFP阳性率显著高于PCT(x2=16.048,P＜0.01),与LC无显著差异.结论HBsAg,HCV-Ag和AFP与肝癌的发生有密切的关系,AFP可能是CTL攻击的主要靶抗原.但血清中高浓度的AFP可能阻断了CTL的作用.因此,用足量的抗AFP抗体来治疗AFP阳性肝癌可能是一条有希望的途径.     

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。     

新生儿乙型肝炎疫苗普遍接种的长期免疫效果

目的 观察新生儿乙型肝炎(简称乙肝)疫苗普遍接种预防儿童期乙型肝炎病毒(HBV)感染的长期免疫效果和对儿童乙肝发病的影响。 方法 1986年起在乙肝高发区隆安县实施不筛检母亲HBsAg、新生儿普遍接种常规剂量乙肝疫苗的免疫方案。采用出生队列定群随访、横断面调查和监测乙肝发病情况的方法对血源乙肝疫苗和重组酵母乙肝疫苗的保护效果进行观察。 结果 血源乙肝疫苗免疫后1～1 3年HBsAg阳性率为0.7％～2.9％,平均1.7％,保护率为83.5％～96.6％,HBV感染率为1.1％～5.1％,平均2.4％,保护率为93.5％～98.4％。重组酵母乙肝疫苗免疫儿童的HBsAg阳性率为1.8％～2.4％,平均2.0％,保护率为78.4％-85.2％。免疫实施14年后, 1～14岁人群乙肝发病率为1.5/10万,比历史对照同龄者减少了91.8％;未免疫儿童发病率为14.4/1 0万,与历史对照差异无显著性,免疫儿童中无乙肝病例发生,保护率为100％。 结论 新生儿乙肝疫苗免疫后13年内不必加强免疫,重组酵母乙肝疫苗与血源性乙肝疫苗的保护效果相似,乙肝疫苗预防作用已初见成效。     

重组酵母乙型肝炎疫苗和DNA疫苗交互免疫研究

目的 为更有效地激发对乙型肝炎表面抗原体液免疫和细胞免疫反应,更有效地防治乙型肝炎。方法 以重组酵母乙型肝炎疫苗和HBs-DNA疫苗作为初次免疫,再分别以DNA疫苗和重组酵母乙型肝炎疫苗交互加强免疫,于加强免疫后2周以ELISA检测抗-HBs,乳酸脱氢酶法检测细胞毒性T淋巴细胞(CTL)反应。 结果 先用重组酵母乙型肝炎疫苗免疫,再用HBs-DNA疫苗加强时抗体A值为0.38,效靶比为100:1时,CTL值为36％;先用HBs-DNA疫苗免疫,再用重组酵母乙肝疫苗免疫时抗体A值为0.32,CTL值为27％。两次重组酵母乙型肝炎疫苗免疫后的抗体A值为0.48,CTL反应值为1.5％;两次HBs-DNA疫苗免疫后A值为0.24,CTL反应值为68％。 结论 乙型肝炎表面抗原能增强DNA疫苗的抗体反应,DNA疫苗能增强重组酵母乙型肝炎疫苗的CTL反应,两者交互免疫可得到更好的免疫效果。     

Seroepidemiology of hepatitis B virus infection and impact of vaccination

AIM: To investigate hepatitis B virus (HBV) prevalence in the general population in China.METHODS: A total of 148931 individuals were investigated by multistage random sampling in Eastern China. Data were collected on demographics and hepatitis B vaccination history, and serum was tested for hepatitis B surface antigen (HBsAg) by ELISA.RESULTS: A total of 11469 participants (7.70%, 95%CI: 7.57%-7.84%) were positive for HBsAg. HBsAg prevalence was 0.77% among children < 5 years old but increased progressively from adolescents (1.40%-2.55%) to adults (5.69%-11.22%). A decrease in HBsAg prevalence was strongly associated with vaccination and familial history of HBV among both children and adult groups. Meanwhile, HBsAg risk in adults was associated with invasive testing and sharing needles. The HBV immunization rate among participants aged < 20 years was 93.30% (95%CI: 93.01%-93.58%). Significant difference in HBsAg prevalence appeared between vaccinated and unvaccinated participants (3.59% vs 10.22%).CONCLUSION: Although the national goal of HBsAg prevalence < 1% among children < 5 years old has been reached, immunization programs should be maintained to prevent resurgence.     

Persistent and transient hepatitis B virus (HBV) infections in children born to HBV‐infected mothers despite active and passive vaccination

Summary. Combined passive and active immunization for newborns very effectively prevents perinatal hepatitis B virus (HBV) infections. In the Netherlands, babies born to hepatitis B surface antigen (HBsAg)‐positive women receive passive immunization with hepatitis B and at least three active HBsAg vaccinations. Serological testing for the presence of HBV markers was offered for all infants born to HBsAg‐positive mothers between January 2003 and July 2007, after completion of their vaccination schedule. About 75% of the infants (n = 1743) completed their HB‐vaccination schedule and participated in the serologic evaluation. Twelve of them (0.7%) were found to be HBV infected. Furthermore, we identified three older children with high levels of anti‐HBc, anti‐HBs and anti‐HBe, while they were HBsAg and HBV DNA negative. This serologic profile is evidence for a resolved HBV infection. In the group of older children (1.5–5 years of age, n = 728), about half of the HBV‐infected children (3 of 7) had already cleared their infection at the time of sampling. For a proper evaluation of the efficacy of a new intervention programme to prevent vertical HBV transmission, it is also important to analyse the HBV markers in serum collected when the children are older than 1.5 years. In a programmatic setting, all children born to HBV‐infected mothers should be tested not only for the level of anti‐HBs but also for the absence of HBsAg, because 2 of the 12 HBV‐infected children (17%) had a high level of anti‐HBs.     

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.     

Effectiveness of hepatitis B vaccination in babies born to hepatitis B surface antigen-positive mothers in Italy

This study examined 522 children born to hepatitis B surface antigen (HBsAg)-positive mothers from 1985 through 1994 and evaluated the protection provided by anti-hepatitis B virus (HBV) immunization at birth. Babies were given hepatitis B immunoglobulin and hepatitis B vaccine at birth. At 5-14 years after immunization, 17 children (3.3%) were anti-HB core antigen positive, and 3 also were HBsAg positive. One carrier child had a double mutation, with substitution of proline-->serine at codons 120 (P120S) and 127 (P127S) within the a determinant of HBsAg. Of the 522 children, 400 (79.2%) of 505 still had protective anti-HBsAg titers > or =10 mIU/mL. Thus, HBV vaccination of children born to HBsAg-positive mothers is effective and confers long-term immunity. There is no evidence that the emergence of HBV escape mutants secondary to the immune pressure against wild-type HBV is of concern.     

Seroprevalence of Hepatitis B and C among Children in Endemic Areas of Turkey

Background and Aims

Hepatitis B virus (HBV) and Hepatitis C virus (HCV) infections are major worldwide public health problems. The objectives of this study were to evaluate the seroprevalence and epidemiological profile of hepatitis B and hepatitis C, to determine the impact of the national vaccination programme against hepatitis B on the prevalence of the hepatitis B surface antigen (HBsAg) carrier and the antibody to hepatitis B surface antigen (anti-HBs) occurrence rate among 0-14 year-old children in southeast Turkey.

Methods

The seroprevalence of hepatitis B and hepatitis C markers was evaluated retrospectively in a group of 10,391 children who were admitted to a tertiary hospital, the Diyarbakir Education and Research Hospital, from January 2005 to December 2008, in order to obtain a better understanding of the regional hepatitis seroprevalence. Children were divided into three different age groups: pre-education period (0-6 years), primary school period (7-12 years) and secondary school period (13-14 years). Samples were analyzed for HBsAg, hepatitis B e antigen (HBeAg), antibody to HBeAg (anti-HBe), anti-HBs positive/antibodies to hepatitis B core antigen (anti-HBc) positive, isolated anti-HBs and antibodies to Hepatitis C virus (anti-HCV) using a commercially available enzyme-linked immunosorbent assay (ELISA).

Results

The mean age of all participants was 8.5± 2 years (range, 0-14). The overall percentages for the prevalence of HBsAg, HBeAg, anti-HBe and anti-HCV were 8.1%, 2.1%, 5.9% and 0.5%, respectively. HBsAg seroprevalence differed significantly by age and gender (P < 0.001). HBeAg seroprevalence was high in the earliest years (P < 0.01). The overall prevalence of anti-HCV did not differ significantly by age (P > 0.5) but differed by gender (P < 0.001). The overall percentages for the prevalence of isolated anti-HBs and anti-HBs positive/anti-HBc positive were 34.2% and 56.9%,respectively.

Conclusions

Our study sheds new light on hepatitis seroprevalence in southeastern Turkey. For example, 1) The seroprevalence of hepatitis B in southeast Turkey is still at its highest rate, according to the averages reported in other studies conducted in the same and different regions of Turkey; and it has not decreased, as reported previously. 2) HBeAg seroprevalence in the earliest years of childhood is high in our study; this is evidence for early acquisition of the infection.3) Isolated anti-HBs positive and anti-HBs positive/anti-HBc positive prevalence is high; given these features, it is obvious that despite the high incidence of vaccinated children, the prevalence of hepatitis B is increasing; and children acquire these viruses in their earliest years. 4) We found the overall prevalence of HCV infection unchanged. Our region has a low endemicity for HCV.     

乙肝疫苗联合乙型肝炎免疫球蛋白接种阻断血清HBsAg阳性母亲HBV母婴传播效果分析*

目的 分析乙肝疫苗联合乙型肝炎免疫球蛋白（HBIG）接种阻断血清HBsAg阳性母亲乙型肝炎病毒（HBV）母婴垂直传播的效果。方法 在血清HBsAg阳性母亲所分娩的712例新生儿中,356例接受标准乙肝疫苗,另356例在接种乙肝疫苗的同时,接受 HBIG接种,比较1~10岁儿童接种成功率和HBV母婴垂直传播阻断率。结果 在56例1~2岁、234例3~4岁、249例5~6岁、135例7~8岁和38例9~10岁年龄组儿童,血清抗-HBs阳性率分别为89.3%、87.6%、81.1%、83.7%和76.3%,HBsAg阳性率分别为0.0%、0.4%、0.4%、1.5%和2.6%,各年龄组比较,无显著性统计学差异（P>0.05）;联合接种与乙肝疫苗接种组血清抗-HBs阳性率分别为84.3%和64.3%,血清HBsAg阳性率分别3.1%和15.2%,两组差异显著（P<0.05）;在血清HBsAg/HBeAg双阳性母亲所分娩的儿童,246例联合接种组血清HBsAg阳性率为1.6%,显著低于162例只接种乙肝疫苗组的11.7%（P<0.05）,而在血清HBsAg阳性母亲所分娩的儿童,110例联合接种与194例只接种乙肝疫苗组比,血清HBsAg阳性率无显著性差异（2.7%对6.2%,P>0.05）。结论 对血清HBsAg/HBeAg双阳性母亲所分娩的新生儿,给予乙肝疫苗联合HBIG接种可能更有效地阻断HBV母婴垂直传播。     

Is There Need for a New Hepatit?s B Vaccine Schedule for Children with Celiac Disease?

Background

Celiac disease (CD) is an autoimmune disease characterized by immunemediated inflammatory damage of the small intestinal mucosa, precipitated by the ingestion of gluten-containing foods. Since human leucocyte antigen DQ2 (HLA-DQ2) is a marker of nonresponsiveness to hepatits B virus (HBV) vaccine, CD may also be associated with this nonresponsiveness.

Objectives

The aim of this study was to compare the responses to HBV vaccine between children with CD and healthy children. We also investigated the relationship between the patients’ responses to hepatitis B vaccine, the clinical presentation of CD, and dietary compliance in the patients.

Patients and Methods

We recruited 52 children with CD and 20 age- and sex-matched healthy children who received HBV vaccination according to the standard immunization schedule. The production of specific antihepatitis B surface antigen (HBsAg) antibodies was evaluated in all patients and control participants. Subjects with less than 10 IU/L anti-HBs were consided nonresponders to the vaccination.

Results

31 of the 52 patients (59.6%) were female and 21 (40.4%) were male. The mean age of the CD patients was 10.7 ± 4 years (range, 4–18 years). Anti-HBs titers were positive in 32 (61.5%) patients and negative in 20 (38.5%) patients, while they were positive in 18 (90%) of the children in the control group (P < 0.05). We found statistically significant differences between negative anti-HBs titers, clinical presentation of CD, and dietary compliance in patients with CD (P < 0.05).

Conclusions

Nonresponsiveness to hepatitis B vaccination was more frequently found in children with CD than in the control group. Therefore, the response to HBV vaccination should be investigated in children with CD, and a different immunization schedule may need to be developed. Further, compliance to the prescribed gluten-free diet (GFD) may improve the immune response to HBV vaccination in children with CD.