慢性乙型肝炎病毒（HBV）感染是慢性肝病的重要病因，也是我国肝硬化和肝癌高发病率的主要原因，而母婴传播是感染HBV的重要途径。第29届亚太肝病学会年会（APASL2020）上，马来西亚马来亚大学Rosmawati Mohamed教授分享了妊娠期慢性HBV感染的最新进展，并就相关热点问题接受了《国际肝病》的专访。现报道如下，英文实录详见文末。
如何阻断HBV母婴传播，基本策略有哪些？
阻断HBV母婴传播的重点是确保HBsAg阳性的母亲不会将病毒传播给婴儿，如果婴儿于出生时发生感染，则转变为长期感染或终生感染的几率很高。
要阻断HBV母婴传播，必须强调在分娩后12小时内尽早注射一剂乙肝免疫球蛋白，加上乙肝疫苗系列的第一剂，全程乙肝疫苗程序包括6个月内注射三剂。这在95%的病例中，有助于预防HBV母婴传播。
然而，有一些研究表明，如果母亲的病毒血症水平很高，发生HBV母婴传播的风险增加很多，因此，为了阻断HBV母婴传播，还需要另外的策略，即于妊娠期间对高病毒载量的母亲给予抗病毒治疗。已经表明，如果在妊娠期间尽早予以抗病毒治疗，可以进一步将母婴传播率降至最低为零，通常于妊娠晚期予以抗病毒治疗。
从传统意义上，我们避免于妊娠早期给予抗病毒药物治疗，主要是因为妊娠早期是胎儿发育期。如果抗病毒治疗仅仅是为了达到阻断母婴传播的目的，通常需要治疗3个月左右，药物可以起效，除非母亲的病毒载量非常高，使母婴传播的风险增加。因此，可能需要于妊娠24周时，尽早开始抗病毒治疗，而不是至妊娠30～32周时，才常规开始治疗。
因为分娩时是发生病毒传播至婴儿的时间，基本上，我们一直在谈论分娩时的病毒量减少，分娩时即可停止治疗。但是由于存在肝炎发作的发生风险，有些母亲可能在分娩后4～12周继续服用抗病毒药物。众所周知，由于分娩后的激素变化，停用抗病毒治疗可能会导致肝炎发作，这一风险可能高达25%。一般来说，肝炎发作的病情轻微，除非存在之前没有发现的进展期肝病或肝硬化情况，在这种情况下，应该延长治疗，而不是在分娩时停止治疗。
孕妇应用抗病毒药物，对胎儿的安全性如何？
抗病毒药物从母体进入新生儿体内的风险很低，这就是为什么应用抗病毒治疗的母亲并不禁忌母乳喂养的原因。一般来说，母亲服用抗病毒药物，对胎儿是安全的。我们要权衡利弊，只准许孕妇服用某些种类的药物，大多数情况下，我们使用B类药物，因为没有动物研究表明存在任何危害。
除了高病毒载量之外，还有哪些因素与HBV围产期传播的高风险有关?
多数研究已经表明，母亲的病毒载量是导致HBV母婴传播风险的最重要因素。但是，必须强调的是，最重要的预防策略仍然是接种疫苗，并且取决于分娩后12小时内及时优化注射乙肝免疫球蛋白和第一剂乙肝疫苗，然后完成全程乙肝疫苗的接种。再次强调，在阻断HBV母婴传播的策略方面，这是最重要的，妊娠期间应用抗病毒治疗是一种附加策略。
如何权衡抗病毒治疗的停药时机和停药后的肝炎发作风险？
大多数情况下，在分娩时停用抗病毒治疗，已经充分阻断了HBV母婴传播的发生风险。虽然有肝炎发作的较小风险，但是，研究表明，将治疗延长至产后12周，对肝炎发作的发生率没有太大影响。即使妊娠期间没有服用抗病毒药物，分娩后也有可能会发生肝炎发作。
何谓“三联消除”策略？
三联消除是促进协调方法的一个框架，不仅消除HBV母婴传播，而且消除HIV和梅毒的母婴传播。消除HBV母婴传播是最新考虑的问题，可以与消除HIV母婴传播的策略相协调，通过综合服务，以进一步预防HBV传播。
以包括中国在内的西太平洋地区为例，早已实施接种乙肝疫苗的目标，从而看到了成效，儿童的HBsAg阳性率已经降至低于1%，反映了在减少HBV感染人数和死亡率方面的巨大益处。
自从引进乙肝疫苗接种规划以来，仅西太平洋地区就减少了700万的HBV相关死亡。如果我们继续这样做，结果将会很好，但是，还不足以实现至2030年，儿童HBV感染率降至0.1%的目标。
因此，我们现在要做的就是扩大阻断HBV母婴传播的范围，我们已经采用一种增量方法，包括对母亲进行HBsAg检测，应用乙肝免疫球蛋白以及母亲应用抗病毒治疗。
原文呈现：（英文所占篇幅易偏大，格式或字体注意调整下）
<Hepatology Digest>: You talked about hepatitis B in pregnancy. Can you give us an overview of the subject?
Dr Mohamed: The main focus is ensuring that mothers who are HBsAg-positive do not transmit the virus to their babies. The risk of having an infection at birth means there is a high chance of chronic infection or lifelong infection.
To break the viral cycle, there must be an emphasis on the birth dose vaccination given within 12 hours of delivery, plus the first dose of the hepatitis B vaccination series, which includes three doses within six months. That can help prevent mother-to-child transmission of hepatitis B in 95% of cases.
However, there are some studies that show that if mothers have a very high viremia, the chance of transmission is much greater. So to prevent transmission, another strategy is needed, whereby mothers with a high viral load are given antiviral therapy during pregnancy. This has been shown to further reduce transmission rates to as low as zero if treated early enough in the pregnancy. This is usually applied in the third trimester.
Classically, we avoid giving drug therapy in the first trimester, mainly because that is the time of fetal development. If given solely for the purpose of preventing mother-to-child transmission, the drugs generally take around 3 months to work, unless the risk is heightened by the mother’s viral load being very high. So, we may need to start therapy as early as week 24 of the pregnancy, instead of the regular 30-32 weeks.
Basically, we have been talking about the reduction of the virus at the time of delivery, because that is when transmission occurs to the infant. Therapy then stops at delivery. Some people may continue on afterwards, from 4-12 weeks after delivery, because of the risk of flares occurring. It is well known that stopping antiviral treatment can lead to viral flares post-delivery due to hormonal changes that occur. This risk can be as high as 25%. Generally, the flares that occur are mild unless there is advanced liver disease or cirrhosis that was not detected earlier, and in those cases therapy should be extended rather than stopped at time of delivery.
<Hepatology Digest>: Is there a risk of creating drug-resistant viral strains by giving antivirals, in the same way that antibiotics might?
Dr Mohamed: The risk of the drug crossing over to the newborn is quite low, which is why breastfeeding is not contraindicated if the mother is on antiviral therapy. In general, it is safe. We only allow certain categories of drugs to be given in association with pregnancy. We are balancing risk and benefit. In most circumstances, we use category B drugs because there are no animal studies that suggest there is any harm.
<Hepatology Digest>: What are the factors besides high viral load associated with a high risk of perinatal transmission of hepatitis B?
Dr Mohamed: Most studies have shown that the maternal viral load is the most important factor. But it must be stressed that the most important preventative strategy is still vaccination, and that relies on the timely optimization of the birth dose within 12 hours of delivery, the first dose vaccine, and then completing the course. It has to be stressed that that is the most important aspect, and the use of antiviral therapy during pregnancy is an add-on strategy.
<Hepatology Digest>: You mentioned stopping the antiviral therapy at a specific time, and also the possibility of flare. Could you elaborate on that a little more?
Dr Mohamed: In most cases, antiviral therapy would be stopped at the time of delivery, and that would be sufficient. There is a slight risk of flares occurring, but studies show that extending therapy to 12 weeks post-delivery does not make a huge difference in incidence. Flares can occur even if you aren’t taking antiviral therapy.
<Hepatology Digest>: You ended your talk outlining the triple elimination strategy. Can you describe that?
Dr Mohamed: Triple elimination is a framework that promotes a coordinated approach for eliminating mother-to-child transmission of not just hepatitis B, but also HIV and syphilis. Hepatitis B is the newest issue to be considered, and it can be coordinated with strategies for HIV, allowing for integration of services to prevent further hepatitis B transmission.
I used the Western Pacific region, which includes China, as an example, where hepatitis B vaccination targets have been implemented early on. Consequently, success has been seen early with a reduction in HBsAg prevalence to <1% in children, which reflects tremendous benefits in reducing the number infected as well as mortality. There has been a reduction of seven million deaths in the Western Pacific alone since introducing hepatitis B vaccination programs.
If we continue on in this way, the results will be excellent, but will not be good enough to achieve the 2030 target of 0.1% prevalence of hepatitis B amongst children.
So what we want to do now is expand prevention, and we have introduced an incremental approach involving testing mothers for HBsAg, introducing hepatitis B immunoglobulin, as well as antiviral therapy for the mothers.
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