新生儿的极低剂量乙肝疫苗接种:对流行控制的经济选择

乙肝病毒携带者母亲的儿童,HBsAg阳性者约占20%,而大多数病例是来自HBsAg阳性儿童的交叉感染,因此,控制感染的流行,不能将注意力完全集中于母亲为乙肝病毒携带者的婴儿,对婴儿普遍地进行免疫接种才是真正的预防对策。由于每次接种10μg疫苗价格昂贵,并指出更小剂量的疫苗亦可取效,促使我们试用极小剂量(1μg 与2μg)的疫苗以观察其效果。研究对象为新西兰北岛某地区的新生儿,按随机顺序用1μg或2μg疫苗于新生儿出生后第1周,第6周及第5个月分别注射3次,头两次注射于大腿,第3次于三角肌。母亲为乙肝病毒携带者的婴儿,不列为研究对象。所有婴儿于出生后7～10月采血检测。HBsAg用反相被动血凝试验(RPHA)及酶免疫测定(EIA)。抗-HBs测定用RPHA,滴度<1/16为阴性。所有婴儿血清均用EIA行抗-HBc检测,如为阳性再用放射免疫测定(RIA)进行确定。结果表明,1μg疫苗注射组29例中,25例出现抗-HBs,除去3例滴度较低外,22例(76%)获满意效果。2μg疫苗注射组32例中,抗-HBs阳性者为     

新生儿宫内感染乙型肝炎病毒抗原阳性阴转病例报告与分析

乙型肝炎(乙肝)病毒感染是一个很严重的世界性公共卫生问题,我国是乙肝病毒(HBV)感染的高发流行区,近年来虽有大量的关于宫内阻断的研究,但仍有相当数量的阻断失败者[1]。寻找有效的方法使新生儿宫内感染HBV者抗原阳性阴转对降低乙肝发病率,提高人口素质有重要意义。资料与方法2002年10月至2005年11月对在我院出生的母亲为HBV携带者中检测新生儿静脉血HBV抗原,即乙肝表面抗原(HBsAg)和乙肝e抗原(HBeAg),共检出新生儿HBV抗原阳性11例,追踪了10例。这10例新生儿母亲HBsAg和HBeAg双阳性3例,HBsAg单阳性7例。所有HBV抗原阳性新生…     

乙型肝炎病毒宫内感染的探讨

对HBsAg(+)母亲34例和HBsAg(-)母亲21例,在产时和所生新生儿进行系列血清观察,用ELISA法检测HBVM(HBsAg、抗-HBs、HBeAg、抗-HBe、抗-HBc),同时测肝功能(SALT、TTT),并随访到1月龄。发现HBsAg(+)母亲组持续抗原血症1例,HBVM阳性伴ASLT升高8例,提示宫内感染率为26.5％(9/34)。HBsAg(-)母亲组HBVM及肝功均正常。两组差异显著(X~2=4.85;P<0.05)。     

新生儿乙型肝炎病毒血清标志物异常的分析

目的探讨乙型肝炎病毒(HBV)血清标志物异常新生儿的转归。方法筛选HBV血清标志物异常新生儿28例,其母乙肝表面抗原(HbsAg)、乙肝e抗原(HbeAg)、乙肝核心抗体(HbcAb)均阳性;其中21例新生儿HBsAg、HBeAg、HBcAb均为阳性组成垂直传播组;另7例新生儿HBeAg、HBcAb阳性而HBsAg阴性,组成可疑组。HBV血清标志物检测采用时间分辨免疫荧光法,HBV-DNA采用荧光定量聚合酶链反应。结果可疑组新生儿的血清HBeAg和HBsAg水平均低于垂直传播组,差异均有统计学意义(P0.05)。可疑组新生儿出生后3个月复检HBeAg水平为(0.55±0.19)PEIU/ml,低于出生后7 d内检测结果[(4.02±2.00)PEIU/ml],差异有统计学意义(P0.05)。结论对于HBV血清标志物异常母亲及新生儿,早期干预有积极意义。     

乙型肝炎免疫球蛋白阻断HBV宫内感染的疗效及其适应症研究

目的研究乙型肝炎免疫球蛋白(HBIg)阻断HBsAg阳性孕妇HBV宫内感染的疗效并探讨其适应症.方法86例HBsAg阳性孕妇随机分为治疗组(n=40)和对照组(n=46),均在妊娠28周时抽取静脉血检测HBsAg、HBeAg和HBV DNA.治疗组自28周开始每4周肌注一次HBIg(200IU)直至分娩.对照组不给予上述药物.新生儿出生后即取静脉血检测HBsAg.结果治疗组新生儿HBsAg阳性率明显低于对照组.HBeAg阳性和阴性孕妇均可发生宫内感染,但HBeAg阳性孕妇所生新生儿HBeAg阳性率明显高于HBeAg阴性者.而两组中HBV DNA阴性孕妇均未发生宫内感染.结论HBIg能有效降低HBsAg阳性孕妇的宫内感染发生率,HBV DNA检测可以作为是否应用HBIg的指针.     

新生儿外周血单个核细胞乙型肝炎病毒DNA检测的临床意义

目的探讨HBsAg阳性产妇新生儿外周血单个核细胞(PBMC)乙型肝炎病毒(HBV)感染率、影响因素及检测的临床意义。方法50例HBsAg阳性产妇和其新生儿为研究组,另18例血清乙肝标志物均阴性者为对照组。采用套式聚合酶链反应(n-PCR)法分别检测产妇、新生儿血清及PBMCHBV-DNA。结果HBsAg阳性母亲血清及PBMCHBV-DNA检出率分别为60·0%和40·0%;其新生儿血清及PBMCHBV-DNA阳性率分别为46·0%及30·0%;其中仅血清阳性10例,仅PBMC阳性2例,血清和PBMC均阳性13例。对照组母儿血清及PBMC中未检出HBV-DNA。新生儿PBMCHBV-DNA阳性率在母血清HBeAg、HBV-DNA阳性组高于阴性组(P<0·05,P<0·01);母PBMCHBV-DNA阳性组高于阴性组(P<0·01);母血清和PBMCHBV-DNA均阳性组高于仅血清阳性组(P<0·01);新生儿血清HBV-DNA阳性组高于阴性组(P<0·05)。结论HBsAg阳性母亲新生儿HBV-DNA感染率为30·0%;其感染率与母、儿血清病毒血症水平及孕妇PBMCHBV-DNA状态有关,检测出新生儿PBMCHBV-DNA具有重要临床意义。     

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目的 探讨乙型肝炎病毒携带产妇所生新生儿血清乙型肝炎病毒标志物(HBV-M)转归.方法 2001年3月至2006年3月在暨南大学附属第一医院进行产前检查的500例HBsAg阳性产妇所生新生儿,根据母亲HBeAg状态分为HBeAg阳性组144例,HBeAg阴性组356例.两组新生儿在出生12 h内均注射乙型肝炎免疫球蛋白100 IU,并按常规0、1、6方案分别在出生时、1月龄和6月龄注射基因重组乙型肝炎疫苗5μg,注射主被动免疫前分别抽取外周静脉血检测HBV-M.结果 两组新生儿出生时外周血HBsAg、HBeAg均阳性者分别为24例和9例,追踪至6月龄时HBsAg阳性例数分别为10例和5例,HBsAg阴转率差异无统计学意义.两组新生儿出生时HBsAg阳性、HBeAg阴性者分别为4例和21例,追踪至6月龄时,HBsAg阴转率分别为100%和85.7%.出生时HBsAg阴性、HBeAg阳性者,HBeAg阳性组为29例,占20.1%,显著高于HBeAg阴性组比例(P＜0.01),其6月龄HBsAg阳转率为6.9%,明显低于HBeAg阴性组(P＜0.01).在接受全程主被动免疫的情况下,HBeAg阳性组新生儿6月龄HBsAg和HBsAb阳性率分别为9.7%和67.4%,HBeAg阴性组分别为3.1%和78.1%,两组比较差异有统计学意义(P＜0.05).结论 新生儿出生时外周血HBsAg阳性不能作为判断宫内感染的指标,HBeAg阳性新生儿预后与母亲HBeAg状态密切相关,母亲HBeAg阳性会抑制新生儿对乙型肝炎疫苗的反应.     

妊娠晚期乙肝孕妇注射乙肝免疫球蛋白对阻断乙肝病毒母婴传播的作用

目的 探讨慢性乙肝病毒感染的孕妇于妊娠晚期注射乙肝免疫球蛋白(HBIG)对阻断乙肝病毒母婴传播的效果.方法 将慢性乙肝病毒携带者或慢性乙肝孕妇及其所生新生儿分为2组,A组孕妇于孕期第28、32及36周时分别肌肉注射HBIG 200 IU;B组孕妇未注射HBIG.分别检测两组孕妇及其所生新生儿血清乙肝病毒标志物(HBVM)及乙肝病毒DNA(HBV DNA).结果 A组孕妇378例,共分娩新生儿378例,其中新生儿血HBV DNA>500 copies/ml 17例,新生儿宫内感染发生率为4.497%;B组孕妇391例,共分娩新生儿391例,新生儿血HBVDNA>500 copies/ml 17例,新生儿宫内感染发生率为4.348%(X<'2>=0.005 6,P>0.05).血清抗-HBs阴性的孕妇所生新生儿中,A组有9例血清抗-HBs阳性,B组未见血清抗-HBs阳性(X<'2>=7.474,P<0.05).结论 给慢性乙肝病毒感染的孕妇于妊娠晚期注射HBIG 3次,每次200 IU不能明显降低新生儿发生乙肝病毒宫内感染的机会,但部分新生儿可获得血清抗-HBs.HBIG在慢性乙肝病毒感染妊娠妇女中的应用尚待进一步探讨.     

乙型肝炎高危儿免疫预防效果及乙肝病毒母婴传播影响因素分析

目的 分析乙型肝炎病毒(HBV)母婴传播影响因素及乙肝高危儿免疫预防的效果,为儿童乙肝防治提供科学依据。方法 回顾性调查539例HBsAg阳性产妇及其6个月至5岁的乙肝高危儿551例,并检测乙肝高危儿的乙肝标志物,分析乙肝病毒母婴传播的影响因素。结果 乙肝疫苗接种率为100%,96.6%联合注射了乙肝疫苗和乙肝免疫球蛋白(HBIG)。各年龄段乙肝高危儿的HBsAg阳性率差异无统计学意义;HBsAb阳性率随年龄增长逐步下降 (P<0.01)。高危儿母亲为HBsAg、HBeAg双阳性者较单纯HBsAg阳性的乙肝感染率高 (15.1% vs 0.2%,P<0.01)。单纯接种乙肝疫苗的高危儿乙肝感染率 (28.6%)高于联合免疫注射者 (2.8%),P<0.01。结论 乙肝高危儿HBsAb阳性率随年龄增高逐渐下降。母亲HBsAg、HBeAg双阳性和出生未联合免疫注射是乙肝病毒母婴传播的危险因素。     

乙型肝炎病毒感染的预防

乙型肝炎表面抗原(HBsAg)阳性母亲所生的婴儿,也常有乙型肝炎病毒(HBV)感染。许多这种新生儿将成为慢性HBV的携带者。其中约1/4在其后将发展成肝硬变或肝细胞性肝癌。此种围产期的感染能通过新生儿的免疫予以预防。本文并推荐对高危婴儿的处理方法。 HBsAg的母亲如果也是乙型肝炎e抗原(HBeAg)阳性时,则她所生的婴儿约90％发生围产感染。母亲是HBeAg阴性或她们对HBeAg有抗体,其婴儿有较少的危险,但仍能受感染。受感染的婴儿通常要在生后几周才变成HBsAg阳性。虽然他们发生黄疸或急性肝炎是罕见的,但转氨酶水平的升高则常见。因为他们是持     

Hepatitis B virus infection in pregnant mothers and its transmission to infants

Screening for serological markers of hepatitis B virus infection was done on 500 pregnant mothers. HBsAg, AntiHBs and HBeAg were done. HBsAg was positive in 3.6%, AntiHBs in 17.4% and HBeAg in 0.4% cases. The infants born to the asymptomatic HBsAg carrier mothers were followed upto 6 months to determine the vertical transmission of HBV infection. Rate of transmission of infection from HBsAg positive mothers to infants were 16.66% irrespective of HBeAg status, whereas it was nearly 100% in case of HBeAg positive mothers. All of the HBsAg positive infants developed the antigenemia between 3–6 months of age, supporting the hypothesis that intrapartum transmission is the major mode of vertical transmission.     

A study of immunoprophylaxis failure and risk factors of hepatitis B virus mother-to-infant transmission

Hepatitis B virus (HBV) infection is of high prevalence in China. Mother-to-infant transmission is the major route for HBV transmission and subsequent chronicity. This study aimed to investigate current HBsAg-positive rate among pregnant women and immunoprophylaxis outcome in China. Multicenter prospective study was conducted in 10 centers. From 2008 to 2012, 67,720 pregnant women were screened and 1,150 HBsAg-carrier mothers and their infants aged 8–12 months were studied in four out of all centers, among whom HBV markers (HBsAg, HBsAb, HBeAg, HBeAb, and HBcAb) and HBV DNA (in three centers) were measured. The results showed that HBsAg-positive rate of pregnant women was 6.7 % (4,533/67,720) and infants’ immunoprophylaxis failure rate was 3.4 % (39/1,150). Immunoprophylaxis failure infants were all born to mothers of HBeAg-positive and HBV DNA ≥6 log₁₀?copies/ml. Among infants of HBeAg-positive mothers, multivariable analyses showed the following: mother’s age <28 years vs ≥28 years, RR?=?0.157, 95 % confidence interval (CI) [0.067, 0.369], p?=?0.000; Neonates receiving vaccine vs vaccine plus hepatitis B immune globulin (HBIG), RR?=?0.371, 95 % CI [0.167, 0.825], p?=?0.015. Pregnant women receiving HBIG in the third trimester, vaginal delivery and breastfeeding had no significant effects on HBV mother-to-infant transmission. Conclusions: Pregnant women are still of high HBsAg prevalence in China. HBV mother-to-infant transmission still occurs after passive-active immunization. Pregnant women of high HBV replication levels are the major risk population of HBV mother-to-infant transmission. Passive-active immunization is necessary for neonates of HBeAg-positive mothers. Mother’s age <28 years and neonate receiving vaccine only were the risk factors for HBV mother-to-infant transmission. Breastfeeding did not put children at risk of mother-to-infant transmission.     

Lack of evidence for transplacental transmission of HBV infection by HBsAg-carrier mothers

The possibility of transplacental transmission of HBV infection was investigated in 54 HBsAg-carrier Saudi mothers and their newborns. Controls were 60 Saudi mothers with previous exposure to HBV, and their newborns. Thirteen cord blood samples were HBsAg-positive by ELISA, including three from mothers with previous exposure to HBV, compared with one sample which was HBsAg- and HBeAg-positive and three samples which were only HBeAg-positive. Eight of the 13 cord blood samples which were HBsAg-positive by ELISA were haemolysed sera and were found to be HBsAg-negative by RIA and RPHA. None of the infants' sera, taken within 1-4 days of delivery, was positive for HBsAg or IgM anti-HBc. These results indicate that HBV markers in cord blood are either false-positive or due to contamination by maternal blood rather than an indication of in utero infection.     

预防乙型肝炎病毒母婴传播的随机对照研究

目的探讨乙肝免疫球蛋白（HBIG）预防乙型肝炎病毒（HBV）母婴垂直传播的效果。方法以2001年1月至2005年5月在台州医院产科初次进行妊娠健康检查,HBsAg测定阳性或HBsAg、HBeAg均阳性孕妇作为研究对象,共279例。将单纯HBsAg阳性孕妇与HBsAg、HBeAg双阳性孕妇分别应用随机数表方法随机分组,分别为单阳注射组（n=80）、单阳对照组（n=60）、双阳注射组（n=79）、双阳对照组（n=60）。单阳注射组、双阳注射组于妊娠加周开始肌肉注射HBIG 200U,每4周注射1次,直至临产。两对照组不注射HBIG。4组孕妇所产婴儿,除常规接种乙肝疫苗外,均于出生后16h内和2周肌肉注射HBIG。然后随访并测定婴儿HBsAg。结果单阳注射组、单阳对照组、双阳注射组、双阳对照组所生婴儿HBsAg感染率分别为3％、13％、10％、32％。单阳注射组与单阳对照组之间（x^2=6．07,P〈0．05）,以及双阳注射组与双阳对照组之间婴儿HBsAg感染率（x^2=10．11,P〈0．01）均有统计学意义,注射HBIG组,对单纯HBsAg阳性孕妇及HBsAg、HBeAg双阳性孕妇,出生婴儿HBsAg感染率均显著低于对照组;单阳注射组与双阳注射组之间婴儿HBsAg感染率差异亦有统计学意义,说明HBIG对单纯HBsAg阳性孕妇预防效果优于HBsAg、HBeAg双阳性孕妇。结论HBIG能有效预防母婴传播,降低HBV感染率。因此,妊娠妇女应及时进行健康检查,发现HBV感染阳性,及时采取注射HBIG等有效措施,以促进优生优育。     

Horizontal transmission of hepatitis B virus infection to United States-born children of Hmong refugees.

There is evidence that hepatitis B virus (HBV) transmission continues among Southeast Asian refugees after resettlement. To determine the prevalence of HBV infection (hepatitis B surface antigen [HBsAg] positive or core antibody positive) and modes of transmission in Hmong refugee households in Wisconsin, results of serologic tests were reviewed for 429 US-born children not previously vaccinated with hepatitis B vaccine and 754 of their Asian-born household members. The prevalence of HBV infection was 14% (62/429) among all US-born children, 30% (21/69) among children whose mothers were HBsAg-positive, and 11% (41/360) among children whose mothers were HBsAg-negative. Among children whose mothers were HBsAg-negative, the prevalence of HBV infection increased with increasing age (chi 2 test for trend = 5.6, P = .02) and was related to the household presence of HBsAg-positive sibling(s) (relative risk = 4.0; 95% confidence interval = 1.5, 9.3; P less than .001). Of the 62 infected children, 13 (21%) lived in households with no HBsAg-positive household members. US-born children of Hmong refugees apparently acquire HBV infection through both horizontal and perinatal transmission. These findings emphasize the importance of routinely integrating hepatitis B vaccine doses into the childhood vaccination schedule for all infants whose parents are from areas where HBV infection is highly endemic. In addition, the findings support the need for pediatricians to consider vaccinating older children (up to age 7 years) whose parents are from HBV-endemic areas.     

Chronicity rate of hepatitis B virus infection in the families of 60 hepatitis B surface antigen positive chronic carrier children: Role of horizontal transmission

It is known that the 5%–10% of adults infected with hepatitis B virus (HBV) develop a chronic infection and that HBV infection acquired at birth by an hepatitis B surface antigen (HBsAg)/hepatitis B e antigen (HBeAg)-positive mother almost invariably leads to chronic infection. Little information is, however, available about the risk of HBV infection acquired in childhood becoming chronic. We have, therefore, studied the chronicity rate of HBV infection in the families of 60 consecutive HBsAg-positive chronic carrier children. Of parents 81.5% and 78.6% of children showed serological evidence of past or ongoing HBV infection. The chronicity rate was significantly higher among children (73.4%) than parents (35.6%). Such a high chronicity rate in these children was not correlated with vertical transmission, since this was reported in only 1.7% of them. It is noteworthy that the chronicity rate of HBV infection was not significantly different between children of HBsAg-positive mothers and those in whom infection must have been horizontally transmitted because their mothers were HBsAg-negative. Although the families studied represent a selected sample and the role of genetic factors could not be excluded, our results seem to show that the most important factor in determining the outcome of infection is the acquisition of hepatitis B during childhood.     

乙型肝炎病毒宫内感染对新生儿外周血细胞因子干扰素γ和白介素4的影响

目的 探讨乙型肝炎病毒(HBV)侵犯新生儿外周血单个核细胞(PBMC)后,对新生儿免疫功能的影响,了解其免疫失败发生的机理.方法 聚合酶链反应法(PCR)检测67对乙型肝炎表面抗原(HBsAg)、乙型肝炎e抗原(HBeAg)阳性孕妇及其新生儿血清和PBMC的HBV DNA.根据新生儿PBMC中HBV DNA分成阴性和阳性组,将新生儿的PBMC分别在植物血凝素(PHA)和纯化HBsAg刺激下进行体外细胞培养,检测培养上清液中干扰素-γ(IFN-γ)、白介素-4(IL-=4)的分泌含量.结果 (1)35例母亲PBMC HBV DNA阳性者其新生儿15例为阳性,母亲与患儿PBMC HBV DNA阳性,差异有显著统计学意义(P＜0.01).(2)新生儿PBMC内HBV DNA阳性组与阴性组比较,纯化HBsAg刺激时,阳性组IFN-γ的分泌量较阴性组低(P＜0.01),IL-4含量显示PBMC HBV DNA阳性组高于阴性组(P＜0.05),PHA刺激时,两组IFN-γ、IL-4含量差异无统计学意义(P＞0.05).结论 PBMC内的HBV DNA可能是HBV母婴垂直传播的一条重要途径;宫内新生儿PBMC感染HBV,IFN-γ特异性反应低下,而IL-4特异性反应增强,细胞调节失衡,可能是新生儿免疫失败和易于免疫耐受的一个重要原因.     

Hepatitis B virus infection

Hepatitis B virus (HBV) infection is a worldwide health problem and may cause acute, fulminant, chronic hepatitis, liver cirrhosis, or hepatocelullar carcinoma (HCC). Infection with HBV in infancy or early childhood may lead to a high rate of persistent infection (25-90%), while the rates are lower if infection occurs during adulthood (5-10%). In most endemic areas, infection occurs mainly during early childhood and mother-to-infant transmission accounts for approximately 50% of the chronic infection cases. Hepatitis B during pregnancy does not increase maternal mortality or morbidity or the risk of fetal complications. Approximately 90% of the infants of HBsAg carrier mothers with positive hepatitis B e-antigen (HBeAg) will become carriers if no immunoprophylaxis is given. Transplacental HBeAg may induce a specific non-responsiveness of helper T cells and HBcAg. Spontaneous HBeAg seroconversion to anti-HBe may develop with time but liver damage may occur during the process of the immune clearance of HBV and HBeAg. Mother-to-infant transmission of HBV from HBeAg negative but HBsAg positive mothers is the most important cause of acute or fulminant hepatitis B in infancy. Although antiviral agents are available to treat and avoid the complications of chronic hepatitis B, prevention of HBV infection is the best way for control. Screening for maternal HBsAg with/without HBeAg, followed by three to four doses of HBV vaccine in infancy and hepatitis B immunoglobulin (HBIG) within 24h of birth is the most effective way to prevent HBV infection. In areas with a low prevalence of HBV infection or with limited resources, omitting maternal screening but giving three doses of HBV vaccine universally in infancy can also produce good protective efficacy. The first universal HBV immunisation programme in the world was launched in Taiwan 22 years ago. HBV infection rates, chronicity rates, incidence of HCC and incidence of fulminant hepatitis in children have been effectively reduced.