妊娠期抗病毒治疗阻断HBV母婴传播研究进展

HBV感染是世界卫生问题,母婴传播是HBV慢性感染的主要途径。HBe Ag阳性孕妇所生婴儿经正规免疫接种后,仍有5%~15%发生HBV感染。现有多项研究证实孕期给予核苷(酸)类似物抗病毒治疗的安全性及有效性,其可提高母婴传播阻断率,改善HBV感染对妊娠和分娩结局的不良影响。本文就HBV DNA高水平孕妇的抗病毒治疗指征、药物选择、服药开始与停止的时间、用药监测、产后哺乳及产后新生儿随访的相关问题进行综述,以期为降低HBV母婴传播提供新的方法。     

分娩方式对高病毒载量的HBV感染母亲母婴阻断的影响

目的 探讨HBV高病毒载量孕妇的分娩方式对母婴阻断结果的影响.方法 选择2012年1月1日—2014年12月31日在我院分娩且HBV DNA≥1×106 copies/ml的孕妇570例,分析其分娩方式,检测所生婴儿出生时和完成全程乙型肝炎疫苗免疫后(7~12月龄)的HBV血清学标志物.结果 570例中,289例(50.7%)剖宫产分娩292例活婴(双胎3例),其中新生儿免疫成功270例(92.5%),免疫无应答3例(1.0%),HBV感染19例(6.5%);281例(49.3%)阴道分娩281例活婴,其中新生儿免疫成功252例(89.7%),免疫无应答4例(1.4%),HBV感染25例(8.9%).阴道分娩组所生婴儿母婴阻断失败率稍高于剖宫产组,但差异无统计学意义(8.9%vs 6.5%,χ2=1.153,P=0.283).结论 分娩方式对HBV从母亲血液渗透到婴儿体内无明显影响,对HBV母婴阻断效果无明显影响.     

替比夫定阻断HBV DNA高载量孕妇母婴传播的疗效和安全性观察

目的评价妊娠早期（12周）应用替比夫定阻断高病毒载量孕妇母婴传播的疗效和安全性。方法选择妊娠12周慢性乙型肝炎孕妇80例,病毒载量均超过1×10^7拷贝/ml。按患者意愿分治疗组（替比夫定组）38例和对照组42例,治疗组口服替比夫定600 mg,1次/d,加用复方甘草酸苷保肝治疗,替比夫定服用至产后12周;对照组不给予抗病毒药物,只给予复方甘草酸苷保肝治疗。两组新生儿出生后均接种乙型肝炎免疫球蛋白200 IU与乙型肝炎疫苗20μg。婴儿7月龄时HBsAg及HBV DNA阳性者为HBV宫内感染。观察两组患者母体HBV DNA水平的变化情况和新生儿HBsAg的阳性率。对两组HBsAg阳性率的差异分析采用卡方检验;组间比较行t（t＇）检验,治疗前后的比较采用配对t检验。结果至分娩前,替比夫定组孕妇HBV DNA、ALT水平明显下降。替比夫定组HBV DNA载量于治疗2周后迅速下降,之后缓慢下降直至分娩。替比夫定组服药至分娩前及分娩后12周HBVDNA水平明显降低（t=29.15、40.06,P〈0.01）,而对照组无明显变化（P〉0.05）。替比夫定组分娩前及分娩后12周HBV DNA水平较对照组明显下降（P〈0.01）。替比夫定组新生儿7月龄时HBV感染率为0,明显低于对照组14.3%,差异有统计学意义（χ2=3.99,P〈0.05）,替比夫定组母婴均无不良事件发生,对照组有2例发生严重肝功能异常。两组孕产妇的剖宫产率、不良妊娠率、产后出血率及新生儿的胎龄、体质量、身长、Apgar评分等,差异均无统计学意义。结论乙型肝炎病毒高载量孕妇孕12周开始应用替比夫定可显著抑制孕妇外周血清HBV DNA水平,降低新生儿HBV感染率,并具有良好的耐受性及安全性。     

替比夫定阻断乙型肝炎病毒母婴传播效果及安全性的荟萃分析

目的 综合评价妊娠期替比夫定阻断HBV母婴传播的效果和安全性. 方法 在数据库中系统检索相关文献,按纳入和排除标准从中选择符合条件的8篇文献,提取资料后采用RevMan5.1软件进行荟萃分析. 结果 共检索到符合标准的文献8篇,共678例.替比夫定组婴儿在出生时HBsAg阳性率和HBV DNA阳性率均明显低于对照组,差异有统计学意义[OR=0.27,95％CI (0.17,0.43),P＜0.00001 ; OR=0.14,95％ CI (0.06,0.32),P＜0.00001];婴儿随访6个月时HBsAg阳性率和HBV DNA阳性率均低于对照组,差异有统计学意义[OR=0.06,95％ CI (0.02,0.22),P＜ 0.00001 ; OR=0.05,95％ CI (0.01,0.25),P=0.0003];婴儿随访12个月时HBsAg阳性率和HBV DNA阳性率均低于对照组,差异有统计学意义[OR=0.13,95％ CI (0.03,0.56),P=0.007;OR=0.08,95％ CI (0.02,0.37),P=0.001];替比夫定治疗前两组孕妇HBV DNA水平差异无统计学意义[OR=0.12,95％ CI (0.00,0.24),P=0.04],分娩前替比夫定组孕妇HBV DNA水平低于对照组,差异有统计学意义[OR=-3.92,95％ CI(-4.90,-2.95),P＜0.00001];替比夫定组和对照组孕妇在服药期间不良反应发生率和婴儿的的不良反应发生率差异无统计学意义[OR=1.72,95％ CI (0.68,4.38),P=0.25;OR=0.69,95％CI(0.04,11.24),P=0.80].结论 高HBV病毒载量的孕妇服用替比夫定抗病毒治疗能够有效阻断母婴传播.     

替比夫定阻断HBV高病毒载量孕妇母婴垂直传播效果观察

目的评价妊娠晚期应用替比夫定(LdT)阻断HBV高病毒载量孕妇母婴垂直传播的效果。方法选择血清HBsAg及HBeAg阳性、肝功能正常且HBV DNA≥1×106拷贝/ml的孕妇,按自愿原则分为LdT组(150例)和对照组(100例)。LdT组孕妇从孕28周起口服LdT600mg/d,至分娩后42天止。对照组患者不用抗病毒药物。观察LdT组患者服药后出现的不良反应,并检测受试者在孕28周及分娩时血清HBV DNA水平。检测所生婴儿出生后6小时内血清HBsAg及HBV DNA情况。结果 LdT组孕妇服药后HBV DNA水平明显低于对照组,差异有统计学意义(t=5.43,P0.001);LdT组的婴儿出生6小时内血清HBV DNA阳性率与对照组比较,差异有统计学意义(χ~2=27.36,P0.0001);对照组HBsAg滴度明显高于LdT组,差异有统计学意义(t=2.25,P=0.03);LdT使用随访期间,未发生严重不良反应且无出生缺陷者。结论 HBsAg、HBeAg阳性且肝功能正常的HBV DNA高病毒载量孕妇妊娠晚期应用LdT抗病毒治疗可显著抑制孕妇血清HBV DNA水平的同时,可有效阻断HBV宫内传播,具有良好的安全性。     

拉米夫定阻断乙型肝炎病毒母婴垂直传播的疗效和安全性观察

母婴垂直传播是HBV的重要传播途径,孕妇血清中HBVDNA水平与宫内感染率有正相关性 [1]。本研究对拉米夫定阻断HBV母婴垂直传播的临床疗效和安全性进行了观察。一、对象与方法1.病例选择:选择 2001年 3月至 2003年 12月在我院就诊孕妇中,孕 28周时B超提示胎儿发育正常,血清HC     

比较替比夫定与拉米夫定治疗慢性乙型肝炎疗效的Meta分析

目的评价替比夫定与拉米夫定对比治疗慢性乙型肝炎（CHB）的疗效。方法检索2007年4月至2010年8月万方数据、维普资讯、中国生物医学文献数据库,根据纳入标准、排除标准,对入选的6篇随机对照试验（RCT）的研究结果,采用RevMan5.0.2软件进行分析。结果与对照组相比,替比夫定能更显著地提高HBV DNA转阴率、HBeAg转阴率、HBeAg血清转换率和ALT复常率：相对危险度（RR）分别为1.39[95%CI（1.26～1.54）,Z=6.45,P〈0.00001]、1.46[95%CI（1.16～1.84）,Z=3.24,P=0.001]、1.47[95%CI（1.12～1.92）,Z=2.77,P=0.006]和1.15[95%CI（1.09～1.22）,Z=4.88,P〈0.00001];且降低耐药率：优势比（OR）为0.31[95%CI（0.20～0.48）,Z=5.15,P〈0.00001];而两组不良事件发生率的差异无统计学意义[OR=1.36,95%CI（0.84～2.20）,Z=1.27,P=0.20]。结论采用替比夫定与拉米夫定对比治疗CHB患者,能更显著地降低HBV DNA,提高HBeAg血清转阴率、转换率和ALT复常率,降低耐药率,且不增加药物不良反应。     

母婴HBV垂直感染与替诺福韦酯阻断治疗

综述了母婴HBV垂直感染及其发生标准预防免疫失败原因、孕期使用替诺福韦酯(TDF)来阻断其母婴垂直感染的策略等最新进展进行综述,为今后开展更多的临床研究及其防治策略提供指导意见,目的是为了更科学地进行临床管理,真正达到HBV母婴"零"传播。     

拉米夫定阻断慢性HBV感染孕妇母婴传播的临床效果和安全性

乙型肝炎疫苗联合乙型肝炎免疫球蛋白(HBIG)对新生儿进行双重免疫虽能明显降低乙型肝炎病毒(HBV)感染率,但仍有20%～30%的新生儿免疫失败,这与宫内感染有关[1].我们近年来对部分慢性HBV感染孕妇使用拉米夫定进行阻断,并对在母婴垂直传播阻断中的效果和安全性进行了观察和总结.     

替诺福韦阻断孕晚期HBV母婴传播的疗效及停药安全性

目的评估乙型肝炎病毒(HBV)高载量孕妇妊娠晚期服用替诺福韦阻断HBV母婴传播的疗效及安全性,观察孕妇服药期间及停药后ALT升高情况。方法选择妊娠26～32周HBV感染免疫耐受期高病毒载量孕妇71例,分为替诺福韦治疗组40例,对照组31例。治疗组孕妇予替诺福韦300mg/d口服至分娩当日停药,对照组不给予抗病毒药物。所有婴儿给予标准联合免疫。若婴儿7个月龄时(或第三针乙型肝炎疫苗注射后1个月)HBsAg阳性或HBV DNA阳性则定义为HBV母婴阻断失败。孕妇在基线、分娩时及产后1、3、6个月分别检测肝功能、HBV DNA水平。采用SPSS17.0进行统计学分析。结果替诺福韦治疗组及对照组母婴阻断成功率分别为100%、90.3%,差异有统计学意义(χ~2=4.042,P=0.044)。治疗组临产时HBV DNA水平较基线时明显下降(t=22.802,P0.001),停药后HBV DNA出现反弹,产后3个月回升至基线水平(t=1.594,P=0.115)。服药期间及停药后6个月内,治疗组患者中有4例(4/40,10.0%)ALT升高,对照组有2例(2/31,6.5%),差异无统计学意义(χ~2=0.284,P=0.594)。治疗组孕妇观察期间无血肌酐及血磷异常情况,两组新生儿一般情况及生长发育良好。结论孕晚期使用替诺福韦治疗可有效阻断HBV母婴传播,孕妇分娩后立即停药整体安全性良好、较少出现肝炎活动。     

Comparison of the efficacy and safety of tenofovir and telbivudine in interrupting mother-to-child transmission of hepatitis B virus

The present study is aimed to evaluate and compare the efficacy and safety of tenofovir (TDF) and telbivudine (TBV) in interrupting hepatitis B virus (HBV) mother-to-child transmission (MTCT), and to provide evidence-based treatment options to clinicians and patients.Hepatitis B e-antigen (HBeAg)-positive pregnant women (644 in total) with high HBV DNA load (≥2 × 10⁵ IU/mL) and who received TDF (n = 214) or TBV (n = 380) in the second or third trimester, or received no treatment (n = 50) were included in this retrospective analysis.HBV DNA levels in mothers at delivery were significantly lower than baseline in the 2 treatment groups. HBV DNA levels in the TDF group were significantly different between the mothers receiving treatment in the second trimester and those receiving treatment in the third trimester; however, significant difference was not observed in the TBV group. The proportion of hepatitis B surface antigen (HBsAg)-positive infants at the age of 7 to 12 months in the TDF, TBV, and control groups were 0.00% (0/174), 0.30% (1/331), and 5.0% (2/40) with a significant difference between the treatment groups and the control group, but no difference between the TDF and TBV group (P > .05). However, no serious adverse events were observed in infants and mothers of all groups.TBV and TDF can effectively reduce the HBV DNA level and MTCT rate in pregnant women with high HBV DNA load (≥2 × 10⁵ IU/mL); both antiviral drugs are safe for infants and mothers. Since TDF was more effective in reducing HBV DNA levels during the second trimester, its use during the period is recommended to prevent HBV MTCT.     

乙型肝炎病毒母婴传播阻断的共识与争议

慢性乙型肝炎因其严重的不良临床结局如肝硬化或肝细胞癌而成为严重的公共卫生问题,而母婴传播是导致慢性HBV感染的最主要原因。尽管HBV阳性孕妇所生的新生儿在出生后24h之内应用了乙型肝炎疫苗和乙型肝炎免疫球蛋白（HBIG）进行联合免疫阻断,仍然有大约10％左右的新生儿感染了HBV,特别是高病毒载量的孕妇。本文将就HBV母婴传播的特点、目前在阻断措施方面达成的共识和存在的争议进行论述。     

HBV lamivudine resistance among hepatitis B and HIV coinfected patients starting lamivudine, stavudine and nevirapine in Kenya

Widespread use of lamivudine in antiretroviral therapy may lead to hepatitis B virus resistance in HIV-HBV coinfected patients from endemic settings where tenofovir is not readily available. We evaluated 389 Kenyan HIV-infected adults before and for 18 months after starting highly active antiretroviral therapy with stavudine, lamivudine and nevirapine. Twenty-seven (6.9%) were HBsAg positive and anti-HBs negative, 24 were HBeAg negative, and 18 had HBV DNA levels ≤ 10,000 IU/mL. Sustained HBV suppression to <100 IU/mL occurred in 89% of 19 evaluable patients. Resistance occurred in only two subjects, both with high baseline HBV DNA levels. Lamivudine resistance can emerge in the setting of incomplete HBV suppression but was infrequently observed among HIV-HBV coinfected patients with low baseline HBV DNA levels.     

Efficacy of switching to telbivudine in chronic hepatitis B patients treated previously with lamivudine

Background: Telbivudine showed greater antiviral suppression than lamivudine in phase II and III clinical trials. Aims: The present phase IIIb, randomized, double‐blind, multicentre global trial assessed the antiviral efficacy and safety of telbivudine switch in chronic hepatitis B (CHB) patients who exhibited persistent viraemia under lamivudine therapy. Methods: HBeAg‐positive and HBeAg‐negative adult patients (N=246) with persistent viraemia [hepatitis B virus (HBV) DNA>3 log₁₀ copies/ml] under lamivudine treatment for 12–52 weeks were randomized (1:1) to continue lamivudine 100 mg/day or switch to telbivudine 600 mg/day for 1 year. Primary endpoint was the reduction in serum HBV DNA levels from baseline at Week 24. Results: The mean reduction in serum HBV DNA levels from baseline with telbivudine was significantly higher than lamivudine at Week 24 (?1.9 ± 0.18 vs. ?0.9 ± 0.27 log₁₀ copies/ml; P<0.001) and maintained through 1 year. The rate of treatment failure was significantly lower (P<0.001) for patients who switched to telbivudine (5%) compared with those who continued lamivudine (20%) after 52 weeks of treatment. In the telbivudine group, treatment failure occurred in only five patients with >24 weeks of prior lamivudine treatment, all associated with pre‐existent lamivudine‐resistant mutations. Genotypic resistance rates were higher in patients continuing lamivudine compared with those who switched to telbivudine with <24 weeks of lamivudine exposure. Both treatments were well tolerated with similar safety profiles. Conclusions: Early (≤24 weeks) switch to telbivudine improves virological outcomes in CHB patients with persistent viral replication under lamivudine treatment.