乙肝病毒与怀孕：一条两条路

StephenW

乙肝病毒与怀孕：一条两条路

    芝商所

资料来源：应对病毒性肝炎管理的关键挑战
玛丽亚·布蒂，医学博士

妊娠期 HBV 感染的管理提出了几个重要的挑战。需要考虑的关键问题是预防 HBV 感染的母婴传播或垂直传播、妊娠对 HBV 感染自然史的影响以及慢性 HBV 感染对妊娠结局的影响。在这篇评论中，我特别针对 HBV 感染和怀孕之间的相互作用提供了我的见解。

妊娠对 HBV 感染自然史的影响
妊娠期间感染 HBV 的一个问题是妊娠对感染自然病程的影响。慢性 HBV 感染的特征在于由 HBeAg 状态、丙氨酸氨基转移酶 (ALT) 水平、HBV DNA 水平和肝损伤程度定义的不同疾病阶段。

在我的诊所，大多数患有慢性 HBV 感染的孕妇都有健康的肝脏，并且处于疾病阶段，称为乙型肝炎表面抗原无活性携带者或 HBeAg 阴性慢性感染。该阶段由 HBeAg 阴性状态（顾名思义）、低 HBV DNA 水平和正常肝功能（正常 ALT 且无其他肝病证据）定义。这些病例在怀孕期间不需要特别监测。

然而，对于患有慢性乙型肝炎且怀孕并患有晚期肝脏炎症和/或纤维化的女性，抗病毒治疗适用于她们自身的健康。除了与预防 HBV 垂直传播有关的考虑之外，孕妇开始抗病毒治疗的适应症通常与未怀孕的患者相同，并且由于肝脏疾病的存在而很少需要治疗。

对于那些确实需要抗病毒治疗来治疗 HBV 的人，推荐的抗病毒药物是富马酸替诺福韦地索普西 (TDF)。在怀孕或计划怀孕时已经接受抗病毒治疗的慢性乙型肝炎女性如果尚未接受 TDF，则应改用 TDF。在疗效高、耐药屏障高的抗病毒药物（恩替卡韦、TDF、艾拉酚替诺福韦）中，TDF在孕期的安全性数据最多。

怀孕被认为是一种免疫耐受状态，并且与调节免疫反应的高肾上腺皮质类固醇水平有关。出于这个原因，在怀孕期间可能会观察到轻微的 ALT 升高而没有临床后遗症。在产后期间，免疫重建可能导致 HBV 肝脏发作。尽管 HBeAg 阳性的女性产后 HBV 发作更为常见，但没有明确的预测指标可以确定哪些女性没有风险。因此，AASLD 的指南建议，所有未接受抗病毒治疗的 HBV 感染孕妇——以及在分娩时或分娩后早期停止抗病毒治疗的孕妇——应在分娩后长达 6 个月内仔细随访，以应对肝炎发作以及HBeAg 血清学转换，可能与耀斑相关。

慢性 HBV 感染对妊娠结局的影响
慢性 HBV 感染对妊娠或新生儿结局没有明确的影响；然而，一些研究观察到慢性HBV感染与早产风险增加、出生体重降低和妊娠糖尿病之间可能存在关联。

肝硬化女性需要更频繁地监测，因为她们面临围产期并发症和不良母婴结局的显着风险。应与肝病专家合作为患有慢性 HBV 感染的孕妇提供医疗护理。

在所有情况下，应告知妊娠的慢性 HBV 感染妇女抗病毒治疗的风险和益处以及 HBV 感染垂直传播的风险。那些在怀孕期间和产后未接受抗病毒治疗的人应密切监测 ALT 耀斑。

StephenW

HBV and Pregnancy: A Two-Way Street

    CME CE

Source: Addressing Key Challenges in Viral Hepatitis Management
Maria Buti, MD

The management of HBV infection during pregnancy presents several important challenges. Key issues to consider are the prevention of mother-to-child or vertical transmission of HBV infection and the effects of pregnancy on the natural history of HBV infection and the effects of chronic HBV infection on pregnancy outcomes. In this commentary, I provide my insights specifically on the interplay between HBV infection and pregnancy.

Effects of Pregnancy on the Natural History of HBV infection
One concern with HBV infection during pregnancy is the effect of pregnancy on the natural history of the infection. Chronic HBV infection is characterized by different disease phases defined by HBeAg status, alanine aminotransferase (ALT) levels, HBV DNA levels, and the degree of liver damage.

In my clinic, most pregnant women with chronic HBV infection have healthy livers and are in the disease phase termed hepatitis B surface antigen inactive carrier or HBeAg-negative chronic infection. This phase is defined by HBeAg-negative status (as the name implies), low HBV DNA levels, and normal liver function (normal ALT and no other evidence of liver disease). These cases require no special monitoring during pregnancy.

However, for women with chronic hepatitis B who are pregnant and have advanced liver inflammation and/or fibrosis, antiviral therapy is indicated for their own health. Outside of considerations related to the prevention of vertical HBV transmission, the indications for antiviral therapy initiation in pregnant women are generally the same as those for patients who are not pregnant, and few require treatment because of the presence of liver disease.

For those who do require antiviral therapy for HBV treatment, the recommended antiviral drug is tenofovir disoproxil fumarate (TDF). Women with chronic hepatitis B who are already receiving antiviral therapy when they become pregnant or when they are planning a pregnancy should be switched to TDF if they are not already receiving it. Among the antiviral drugs with high efficacy and high barrier to resistance (entecavir, TDF, and tenofovir alafenamide), TDF has the most safety data during pregnancy.

Pregnancy is considered to be an immune-tolerant state and is associated with high adrenal corticosteroid levels that modulate immune responses. For this reason, mild ALT elevations without clinical sequelae may be observed during pregnancy. During the postpartum period, immune reconstitution may lead to HBV liver flares. Although postpartum HBV flares are more common among women who are HBeAg positive, there are no clear predictors that can identify which women are not at risk. Therefore, guidelines from the AASLD recommend that all pregnant women with HBV infection who are not receiving antiviral therapy—and those who discontinue antiviral therapy at or early after delivery—should be followed carefully for up to 6 months after delivery for hepatitis flares as well as HBeAg seroconversion, which can occur in association with flares.

Effects of Chronic HBV Infection on Pregnancy Outcomes
Chronic HBV infection has no well-established effects on pregnancy or newborn outcomes; however, some studies have observed a possible association between chronic HBV infection and increased risk of premature birth, lower birth weight, and gestational diabetes.

Women with cirrhosis need to be monitored more frequently because they are at significant risk for perinatal complications and poor maternal and fetal outcomes. Medical care for pregnant women with chronic HBV infection should be provided in collaboration with a hepatologist.

In all cases, women with chronic HBV infection who become pregnant should be informed about the risks and benefits of antiviral therapy and the risk of vertical transmission of HBV infection. Those who are not receiving antiviral therapy during pregnancy and the postpartum period should be monitored closely for ALT flares.