我如何在怀孕期间接受乙肝治疗或如何计划怀孕

StephenW

                                                How I Approach HBV Therapy During Pregnancy or If Planning Pregnancy                                    Source:                 Evolving Options for HBV Therapy: Navigating the New Treatment Landscape            
                                                                                                                                                                                        
                                                                    Natalie H. Bzowej, MD, PhD
                                                                    
                                                               
                                                            Follow Discussion            
        
                                
                                                            Released:  June 8, 2018                    
               
                                
            
        
   
        
   
                                        Deciding when to start HBV treatment for a woman of childbearing age depends on the severity of liver disease and, if she is not already pregnant, when she plans to conceive. Here is how I select the optimal HBV therapy for women who are planning to become pregnant or are already pregnant.
HBV Therapy in Women of Childbearing Age
For women of childbearing age who need antivirals for HBV treatment, I recommend discussing pregnancy issues before starting treatment. If the patient is planning to conceive soon, and she has minimal liver disease, it might make sense to delay therapy until after delivery.
If she is not planning to conceive soon, there are several options with varying treatment lengths. Although not recommended for pregnant women, if she is not pregnant, peginterferon can be given for a defined period of 48 weeks. This treatment often results in clinical remission with HBeAg seroconversion.
Oral antivirals usually require longer-term therapy and have lower rates of HBeAg seroconversion. Among the oral antivirals, I consider tenofovir disoproxil fumarate (TDF) an ideal choice because of its efficacy and high barrier to resistance and because—although no HBV antiviral is approved by the FDA in pregnancy—safety data in pregnancy are available for TDF. Safety data in pregnancy are important even in nonpregnant women because not all pregnancies are planned. By contrast, we currently lack data on the safety profile of tenofovir alafenamide (TAF) or entecavir in pregnancy. And although lamivudine and telbivudine are also considered safe in pregnancy, long-term use has a high risk of antiviral resistance, and resistance with short-term lamivudine in the third trimester has been reported
Newly Diagnosed Chronic HBV in Pregnancy
For pregnant women newly diagnosed with HBV early in pregnancy, American Association for the Study of Liver Diseases guidelines recommend treatment if there is risk of hepatic decompensation. In such cases, TDF is also the best choice based on its efficacy and safety data in pregnancy.
However, many women will have mild disease and be in the immune-tolerant phase of HBV infection. Thus, treatment can often be postponed until after delivery.
Continuing HBV Therapy in Early Pregnancy
Because no HBV antiviral is approved by the FDA for use in pregnancy, we face a dilemma when a woman already receiving HBV therapy becomes pregnant: Should she continue or stop her therapy?
Regarding fetal health, the major concern is the risk of exposure to medication during early embryogenesis. Regarding the woman’s health, the major issue is whether interrupting antiviral therapy will harm short-term and long-term liver outcomes. In my practice, if the woman has advanced fibrosis, I continue therapy because interrupting therapy could put her at risk of developing a flare leading to decompensation—which could also affect the fetus.
When continuing therapy during pregnancy, the dilemma becomes whether to switch to a “safer” agent if the woman is not already receiving TDF. Because we lack safety data for entecavir and TAF, I would consider switching such a patient to TDF.
Preventing Perinatal Transmission
Another consideration is preventing perinatal transmission of HBV infection, which can often be achieved after delivery by giving the newborn both passive immunization with hepatitis B immunoglobulin (HBIG) and immunization with the HBV vaccine. However, almost all vaccine and HBIG failures occur when the mother has very high HBV DNA levels.
For handling these cases, data indicate that treatment in the third trimester helps prevent perinatal transmission. Thus, if a pregnant woman has an HBV DNA of > 200,000 IU/mL, HBV treatment should be considered and initiated towards the end of the second trimester. Women with lower HBV DNA levels and no standard indications do not need treatment.

StephenW

我如何在怀孕期间接受乙肝治疗或如何计划怀孕
来源：HBV治疗的不断发展的选择：导航新的治疗景观
Natalie H. Bzowej博士，博士
跟随讨论
发布时间：2018年6月8日

决定何时开始为育龄妇女开始乙肝治疗取决于肝病的严重程度，如果她还没有怀孕，何时计划怀孕。以下是我如何为计划怀孕或已经怀孕的女性选择最佳的HBV治疗。

HBV治疗对育龄妇女的影响
对于需要抗病毒治疗HBV的育龄妇女，我建议在开始治疗前讨论怀孕问题。如果患者计划很快怀孕，并且她的肝脏疾病很少，那么延迟治疗直到分娩后才有意义。

如果她不打算很快构想，有几种选择，具有不同的治疗长度。虽然不建议孕妇服用，但如果她没有怀孕，可以给予聚乙二醇干扰素48周。这种治疗常常导致临床缓解HBeAg血清学转换。

口服抗病毒药物通常需要长期治疗，并且HBeAg血清学转换率较低。在口服抗病毒药物中，我认为替诺福韦二富马酸富马酸酯（TDF）是一种理想的选择，因为其效力和对抗性的高度障碍，并且因为尽管没有HBV抗病毒药物被FDA批准在妊娠期，怀孕期间的安全性数据可用于TDF。即使在未怀孕的妇女中，怀孕期的安全数据也很重要，因为并非所有的怀孕计划都是如此。相比之下，我们目前缺乏妊娠期替诺福韦艾拉酚胺（TAF）或恩替卡韦安全性资料。尽管拉米夫定和替比夫定在妊娠中也被认为是安全的，但长期使用抗病毒药物耐药性的风险很高，而妊娠晚期对拉米夫定的短期耐药性有报道

新诊断的妊娠期慢性HBV
对于在妊娠早期初次诊断为HBV的孕妇，如果存在肝功能失代偿的风险，美国肝病研究协会指南推荐治疗。在这种情况下，TDF也是根据妊娠期药效和安全性数据的最佳选择。

然而，许多女性患有轻微疾病，处于HBV感染的免疫耐受期。因此，治疗通常可以推迟到分娩后。

在怀孕早期继续HBV治疗
由于没有HBV抗病毒药物被FDA批准用于妊娠，当一位已经接受HBV治疗的妇女怀孕时，我们面临两难困境：她应该继续还是停止治疗？

关于胎儿健康，主要关注的是在胚胎发育早期暴露于药物的风险。关于女性的健康状况，主要问题是中断抗病毒治疗是否会损害短期和长期的肝脏预后。在我的实践中，如果女性患有晚期纤维化，我会继续接受治疗，因为中断治疗可能会使她有发生眩光的风险，导致代偿失调 - 这也会影响胎儿。

在怀孕期间继续接受治疗时，如果女性尚未接受TDF，则会变成是否更安全。由于我们缺乏恩替卡韦和TAF的安全性数据，我会考虑将这样的患者转换为TDF。

预防围产期传播
另一个考虑因素是预防HBV感染的围产期传播，通过给予新生儿被动免疫与乙型肝炎免疫球蛋白（HBIG）并用乙型肝炎疫苗免疫接种，通常可以在分娩后实现。但是，当母亲HBV DNA水平非常高时，几乎所有的疫苗和HBIG都会出现失败。

为了处理这些病例，数据表明，妊娠晚期的治疗有助于防止围产期传播。因此，如果孕妇的HBV DNA> 200,000 IU / mL，则应在孕中期结束时考虑并开始HBV治疗。 HBV DNA水平较低且没有标准适应症的女性不需要治疗。

遥望曙光

关键怎样治疗才能最大程度保护，不传给下一代，我们这一代已经受够了，宁可承担适度风险，也要保障下一代健康，否则宁可不生了。