不同剂量乙肝疫苗联合乙肝免疫球蛋白阻断乙肝母婴传播探讨

目的 探讨乙肝表面抗原(HBsAg)阳性孕妇所生新生儿接种乙肝疫苗的最佳剂量及乙肝免疫球蛋白(HBIG)对预防乙肝宫内感染的作用,探讨免疫失败的原因和对策.方法 对2006年1月至2007年4月初在石家庄市妇幼保健院乙肝母婴阻断产科产前检查、分娩、随访的HBsAg阳性母亲及新生儿839例,根据新生儿出生后接种乙肝基因疫苗(HBac)剂量不同分成2组,A组:269例,孕期注射HBIG;B组:570例,其中孕期注射HBIG组496例,未注射HBIG组74例.观察、比较2组新生儿12月龄乙肝表面抗体(HBsAb)阳性率,乙肝母婴阻断率,观察、分析HBIG的宫内阻断效果.结果 A组269例,免疫失败6例.乙肝母婴阻断率97.77%,12月龄HBsAb阳性率84.39%;B注射HBIG组496例,免疫失败11例,乙肝母婴阻断率97.78%,12月龄HBsAb性率87.70%;B未注射HBIG组74例,免疫失败5例,乙肝母婴阻断率93.24%,12月龄HBsAb阳性率85.14%.A组和B注射HBIG组比较,乙肝母婴阻断率差异无统计学性意义(P>0.05),12月龄HRsAb阳性率分别为84.39%、87.70%,B注射组HBsAb阳性率高于A组;B注射HBIG组与未注射组比较,乙肝母婴阻断率分别为97.78%、93.24%,差异无统计学意义(P>0.05).结论 HBsAg阳性母亲所生新生儿接种乙肝疫苗剂量加倍,12月龄HBsAb阳性率增加;孕20周始注射HBIG可提高乙肝母婴阻断率.母亲血乙肝病毒含量<103拷贝/ml,孕期可不注射HBIG,新生儿出生后接受联合免疫即可;乙肝母婴传播与母血乙肝病毒含量有关,免疫失败的重要原因是宫内感染.     

乙肝免疫球蛋白与乙肝疫苗联用预防乙型肝炎病毒母婴传播的疗效评价

目的:评价乙肝免疫球蛋白(HBIG)与乙肝疫苗联用预防乙型肝炎病毒(HBV)母婴传播的疗效及其对不同HBV-DNA载量的孕妇对母婴传播阻断的影响。方法:选取2016年1月—2017年1月间收治的乙肝表面抗原(HBsAg)阳性孕妇94例资料,按用药的不同将其分为A组50例和B组44例,其中干A组孕妇实施孕期干预阻断(于孕妇孕期28周后每隔4周注射HBIG,连续注射3次),B组孕妇孕期内未实施干预阻断;比较两组孕妇在分娩后6 h给予新生儿注射HBIG,并按照0、1、6月免疫程序接种乙肝疫苗,随访新生儿12月,检测其乙肝标志物水平(HBs Ag、,HBsAb)阳性率的差异;另根据孕妇乙肝病毒基因(HBV-DNA)载量的不同将其分为C组28例和D组66例,比较C组和D组HBV母婴传播HBsAg阻断的差异。结果:A组和B组孕妇婴儿12月月龄时的乙肝表面抗原(HBsAg)阳性率经组间比较其差异均无统计学意义(P>0.05),HBsAb阳性率高于B组(P<0.05);D组孕妇母婴传播阻断率高于C组(P<0.05)。结论:采用联合接种HBIG和乙肝疫苗能阻断HBV母婴垂直传播,但其阻断效果与母体HBV-DNA水平有关。     

妊娠晚期孕妇注射乙肝免疫球蛋白的临床观察

目的探讨妊娠晚期注射乙肝免疫球蛋白(HBIG)对阻断乙型肝炎病毒(HBV)母婴垂直传播的疗效。方法将100例乙肝表面抗原(HBsAg)阳性孕妇随机分为预防组60例和对照组40例。预防组于孕28周起开始予以HBIG200U肌内注射,每4周1次,共3次;对照组产前未注射HBIG。检测并比较2组新生儿宫内感染率,同时观察不良反应发生情况。结果预防组新生儿宫内感染率为6.7%,低于对照组的27.5%,差异有统计学意义(P<0.05)。孕妇及新生儿均未见不良反应,且新生儿无出生缺陷。结论孕妇于妊娠晚期多次注射HBIG进行被动免疫,可有效阻断乙肝母婴传播。     

乙肝表面抗原阳性孕妇肌注乙肝免疫球蛋白预防母婴宫内传播临床观察

目的：观察携带乙型肝炎病毒的孕妇注射乙肝免疫球蛋白（HBIG）预防母婴宫内传播临床疗效。方法：对乙肝表面抗原阳性孕妇自孕28周起多次肌注HBIG60例为预防组及未注射的50例乙肝表面抗原阳性孕妇为对照组，采用酶联免疫法和荧光定量PCR法检测母血HBsAg及其新生儿血HBsAg、抗HBs、HBVDNA。结果：预防组60例新生儿中有54例血清抗HBs阳性与对照组相比差异有显著性（P〈0．05），预防组新生儿血HBsAg、HBVDNA检出率均明显低于对照组。结论：经母亲对胎儿行被动免疫可有效预防乙肝病毒宫内传播。     

乙肝免疫球蛋白联合乙肝疫苗阻断乙肝病毒母婴传播的效果分析

目的分析新干县乙肝免疫球蛋白（HBIG）联合乙肝疫苗阻断乙肝病毒（HBV）母婴传播的效果。方法收集新干县2009年（对照组：仅常规接种乙肝疫苗））和2011年（研究组：采用HBIG和乙肝疫苗联合免疫）各100名乙肝病毒表面抗原（HBsAg）阳性孕妇所产新生儿在周岁时采血进行HBsAg和HBsAb（乙肝表面抗体）测定,并对结果进行分析。结果研究组小孩至1岁时HBsAg阳性率为10．0％;HBsAb阳性率为90％。对照组HBsAg阳性率为84％;HBsAb阳性率为16％,两组比较差异有统计学意义（χ2=9．61,P〈0．01）。结论HBIG联合乙肝疫苗注射可明显降低HBsAg（＋）阳性母亲的子女HBV的感染率,提高HBsAb阳性率,从而有效阻断HBV母婴传播。     

基因乙肝疫苗联合乙肝免疫球蛋白阻断乙型肝炎母婴传播的研究

目的：探索阻断母婴乙肝病毒垂直传播的最佳免疫方案。方法：对本研究的所有乙肝病毒标记物阳性的孕妇于妊娠晚期每月肌注乙肝高价免疫球蛋白200IU，共3次，所有新生儿按预先设计方案给予不同的主动加被动免疫。结果：本研究的乙肝病毒母婴垂直传播阻断率显著高于以往文献报道的阻断率。但乙肝疫苗皮内注射组与肌肉注射组之间的HbsAg阳性率、HbsAb阳性率及抗体滴度差异无统计学意义。结论：孕妇妊娠晚期乙肝高价免疫球蛋白被动免疫，继之所生婴儿基因乙肝疫苗5μg/次（0、1、6方案）加大剂量乙肝高价免疫球蛋白200IU／次（0、1／2、1方案）联合免疫方案可明显提高乙肝病毒母婴垂直传播阻断率。     

乙型肝炎免疫球蛋白联合乙型肝炎疫苗阻断母婴传播途径的临床效果

目的探讨乙型肝炎免疫球蛋白(HBIG)联合乙型肝炎疫苗阻断乙型肝炎病毒母婴传播的临床效果。方法抽选2013年3月至2014年12月到本院接受治疗的乙型肝炎病毒表面抗原(HBs Ag)呈阳性的孕妇168例,新生儿179例。将这些研究对象随机分成两组,观察者与对照组。观察组在生产前被施以乙型肝炎免疫球蛋白联合乙型肝炎疫苗,对照组则未施以此治疗办法。在新生儿出生后进行宫内感染率、免疫阻断情况、HBs Ab阳性率变化对比分析。结果 179例新生儿中,对照组宫内感染率15.73%较观察组5.56%更高,同样对照组免疫阻断情况12.40%较观察组1.11%亦更高。在刚出生时到1年后、3年后的随访中,对照组新生儿HBs Ab阳性率为5.62%、84.27%、86.51%,而观察组为18.89%、95.56%、97.78%,虽然随着新生儿的年龄增长,HBs Ab阳性率有显著提高,但观察组显然优于对照组,且具有统计学意义(P<0.05)。结论应用乙型肝炎免疫球蛋白联合乙型肝炎疫苗,能够高效地阻断乙型肝炎病毒通过母婴这一传播途径,对优生优育有着更积极的意义,值得推广应用。     

母婴阻断对新生儿乙型肝炎病毒母婴传播的观察分析

目的观察母婴阻断对新生儿乙型肝炎病毒母婴传播的效果。方法 95例HBsAg及HBV-DNA双阳性的孕妇及其所生新生儿,分为阻断组65例和对照组30例。阻断组孕妇于孕28、32、36、39周分别肌内注射乙肝免疫球蛋白;对照组无任何治疗。2组新生儿于出生后24h内肌内注射HBIG200U,并于生后常规接受乙肝疫苗主动免疫,即分别于出生后24h内、1个月、6个月分别肌内注射基因重组乙肝疫苗。结果阻断组新生儿HBsAg及HBV-DNA6h、1月龄及6月龄阳性检出率均低于对照组,差异均有统计学意义(P<0.05)。阻断组新生儿HBsAb1月龄、6月龄阳性率高于对照组,差异有统计学意义(P<0.05)。结论 HBV-DNA阳性孕妇有必要采用HBIG和乙型肝炎疫苗联合免疫方案阻断母婴传播。     

阻断乙型肝炎母婴垂直传播的疗效观察

目的观察乙肝免疫球蛋白(HBIG)联合乙肝疫苗阻断母婴垂直传播的疗效。方法选择2002年6月～2003年6月血检HBV阳性105例孕妇作为对照组,2003年6月～2004年6月经血检HBV阳性55例孕妇作为实验组。对照组按0、1、6程序接种乙肝疫苗,实验组产妇产前最后3个月接种乙肝免疫球蛋白,婴儿出生后立即接种HBIGl针,以后按0、1、6程序接种乙肝疫苗。结果对照组大三阳的孕妇新生儿脐血HBsAg阳性率为100%,孕妇不同状态HBV阳性者新生儿脐血HBsAg阳性的总检出率为68.57%,实验组脐血HBsAg阳性检出率为3.6%,对照组脐血HBsAg阳性检出率明显高于实验组,其有非常显著性差异(P<0.01)。结论乙肝免疫球蛋白联合乙肝疫苗阻断乙型肝炎病毒母婴垂直传播疗效显著,认为对高传染性产妇(即HBsAg、HbeAg阳性和/或HBV-DNA阳性)实施产前干预的方案值得临床推广。     

乙肝疫苗接种后HBVM变化情况及感染模式的观察

目的了解人群中感染乙肝的情况和感染模式的变化,了解乙肝疫苗对乙型肝炎病毒传播的控制程度,为评价乙肝疫苗的有效性提供理论依据,为进一步预防乙肝病毒的传播提供数据支持。方法采用随机整群取样的方法,对长春市及周边地区共18325人进行乙肝疫苗接种情况调查,采用ELISA方法检测乙肝血清学指标。结果男女组Hbs Ab阳性率分别为83.13%和86.52%,无显著性差异;城乡组Hbs Ab阳性率分别85.99%和42.00%,具有显著性差异;接种过乙肝疫苗组,Hbs Ab阳性率达91.32%,Hbs Ag阳性率6.43%,而未接种乙肝疫苗组Hbs Ab阳性率仅达53.23%,Hbs Ag阳性率9.14%,两组数据具有显著性差异,具有统计学意义。结论接种乙肝疫苗能够降低感染乙肝病毒的风险,是一种有效控制乙肝传播与发病的方法。但是乙肝疫苗并不能够对机体提供完全的保护,除此之外,正确的预防措施也是控制乙肝传播的必要手段。     

Immunopathogenesis of hepatitis B e antigen negative chronic hepatitis B infection.

Hepatitis B e antigen (HBeAg) negative chronic hepatitis B represents currently the predominant form of chronic hepatitis due to the hepatitis B virus (HBV) in several parts of the world. In this review, recent data regarding the process of HBeAg negative HBV strain selection during the course of chronic HBV infection are presented and the potential virus and/or host-mediated mechanisms that lead to chronic liver necroinflammation, i.e. chronic hepatitis are outlined.     

Treatment paradigms on hepatitis B e antigen-negative chronic hepatitis B patients

The primary goal of treatment in hepatitis B e antigen (HBeAg)-negative patients with chronic hepatitis B (CHB) is potent and durable suppression of hepatitis B virus (HBV) replication. It results in biochemical and histological remission of CHB and is the prerequisite for the prevention of cirrhosis, its life-threatening complications and hepatocellular carcinoma. Responses that are durable after the cessation of treatment are referred to as sustained virological responses, whereas those persisting under therapy are referred to as treatment-maintained virological responses. Treatment paradigms of sustained virological response in HBeAg-negative CHB are practically restricted to conventional IFN-α and pegylated interferons (peg-IFNs), and are limited only to patients with compensated liver disease. Long-lasting maintained virological responses without HBV resistance in HBeAg-negative CHB are achievable by all approved nucleos(t)ide analogues (lamivudine, adefovir and entecavir) in highly variable rates, depending on their potency, rapidity of virological response and genetic barrier to resistance. The maintenance of response under 5 years of adefovir treatment represents the most effective treatment paradigm for HBeAg-negative CHB, whereas such long-term data with entecavir and tenofovir monotherapy may become available in the near future. In patients with lamivudine-resistant HBV mutants, the recommended treatment strategy is to add adefovir at the same time as continuing treatment with lamivudine. There are no treatment paradigms as yet of combination therapy from the very outset with two nucleoside analogues for use in treatment-naive patients.     

Treatment paradigms on hepatitis B e antigen-negative chronic hepatitis B patients

The primary goal of treatment in hepatitis B e antigen (HBeAg)-negative patients with chronic hepatitis B (CHB) is potent and durable suppression of hepatitis B virus (HBV) replication. It results in biochemical and histological remission of CHB and is the prerequisite for the prevention of cirrhosis, its life-threatening complications and hepatocellular carcinoma. Responses that are durable after the cessation of treatment are referred to as sustained virological responses, whereas those persisting under therapy are referred to as treatment-maintained virological responses. Treatment paradigms of sustained virological response in HBeAg-negative CHB are practically restricted to conventional IFN-alpha and pegylated interferons (peg-IFNs), and are limited only to patients with compensated liver disease. Long-lasting maintained virological responses without HBV resistance in HBeAg-negative CHB are achievable by all approved nucleos(t)ide analogues (lamivudine, adefovir and entecavir) in highly variable rates, depending on their potency, rapidity of virological response and genetic barrier to resistance. The maintenance of response under 5 years of adefovir treatment represents the most effective treatment paradigm for HBeAg-negative CHB, whereas such long-term data with entecavir and tenofovir monotherapy may become available in the near future. In patients with lamivudine-resistant HBV mutants, the recommended treatment strategy is to add adefovir at the same time as continuing treatment with lamivudine. There are no treatment paradigms as yet of combination therapy from the very outset with two nucleoside analogues for use in treatment-naive patients.     

乙肝病毒大蛋白在乙型病毒性肝炎诊断中的临床意义

目的探讨乙肝病毒大蛋白（HBV-LP）与HBV DNA、HBeAg的相关性及其检测意义。方法共检测416例乙肝患者血清标本,采用酶联免疫吸附试验检测HBV-LP、乙肝病毒标志物（HBV M）;FQ-PCR定量检测HBVDNA。结果416例HBV感染者血清中,HBV-LP浓度与HBVDNA含量（拷贝数对数）间呈正相关（r=0.358,P〈0.05）;在253份HBV DNA阳性标本中HBV-LP阳性率（90.51%）高于乙肝病毒前S1抗原（HBV PreS1Ag）的阳性率（77.08%）,两者差异有统计学意义（P〈0.05）;在44例HBV感染组中,HBV-LP、HBV DNA、HBV PreS1Ag与乙肝病毒前S2抗原（HBV PreS2Ag）间均有显著相关性（χ2=4.793、3.927、6.769、P〈0.05）;HBeAg阴性组中HBV-LP与HBV DNA间差异有统计学意义（P〈0.05）。结论HBV-LP是判断HBV感染者体内病毒复制程度的可靠指标,HBV-LP与HBVDNA呈正相关,是反映HBeAg阴性HBV感染者体内病毒复制情况新的敏感监测指标。     

Treatment of chronic hepatitis B

Infection with the hepatitis B virus has switched over the last 20 years from the classical HBeAg positive serologic pattern to a HBeAg negative form that is linked, in the Mediterranean basin, with the epidemiologic replacement of the causative wild-type of virus B with mutant variants, whereby mutations in the core-promoter and in the pre-core region prevent the secretion of HBeAg. The wild-type pattern of infection (characterized by relatively high steady level ALT, high HBV-DNA levels and clinically overt liver disease) responds relatively well to Interferon: 3 to 5 mega units daily or 10 mega units every other day for 16 weeks induce anti-HBe seroconversion, normalize the ALT and possibly also eliminate the HBsAg in some 40% of the adults with a minimal (7%) risk of relapse. However, the mutant type infection (anti-HBe positive / HBe Ag negative) is less responsive to Interferon; this has led to the search for novel nucleoside analogues which has currently culminated in the advent of Lamivudine. This competitor of cytidine is 80% bioavailable and devoid of side-effects at the oral dose of 100 mg daily; tolerance continues for therapies up to 3 years. Lamivudine therapy shares with Interferon a rapid decline of ALT accompanied by improvement of histology; at variance with Interferon there is a delayed accumulating seronconversion to anti-HBe and the switch to anti-HBs is rare. Over the long term its activity is abolished by the emergence of specific viral mutations (YMDD mutants) that rekindle the disease. The indications to Lamivudine therapy in HBeAg negative chronic hepatitis B are currently under investigation. Lamivudine is highly efficacious in preventing HBV reinfection in liver transplants.