儿童乙型肝炎管理的最新进展

StephenW

Updates in the management of hepatitis B in children
Ming-Wei Lai & Mei-Hwei Chang
Received 06 Aug 2019, Accepted 25 Oct 2019, Accepted author version posted online: 30 Oct 2019, Published online: 11 Nov 2019

    Download citation https://doi.org/10.1080/17474124.2019.1686975 CrossMark Logo CrossMark


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ABSTRACT

Introduction: Universal infant hepatitis B virus (HBV) vaccination program has reduced HBV infection dramatically in vaccinated young generations. Management of chronically infected children is still challenging concerning high viral load with mostly mild diseases, yet with a nonnegligible proportion of advanced diseases, and long-term effect of antivirals. However, with more potent antivirals approved for pediatric patients, to start antivirals earlier in eligible patients may benefit their outcomes. This review aimed to update the current management of chronic hepatitis B in children.

Areas covered: This review covered the natural history of chronic HBV infection, management of chronic hepatitis B in children from the past to the present, current consensus on the treatment of chronic hepatitis B in children, controversies in cessation of oral antivirals, and management of special populations such as pregnancy and co-infections.

Expert opinions: Without contraindication, peginterferon is recommended for immune-active children ≥ 3 years old. For those intolerant, decompensating or preferring oral therapy, first-line Nucleos(t)ide analogs (NUC), Entecavir or Tenofovir, may be applied. For immune-tolerant or inactive carriers, close monitoring is crucial. When to stop NUCs and novel therapies for HBV cure await further research.
KEYWORDS: Nucleos(t)ide analogs, pegylated interferon, HBeAg seroconversion, HBsAg loss, reactivation, liver fibrosis, immune tolerant, immune clearance, HBeAg-negative hepatitis
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Article highlights

    Most chronic HBV-infected children are mild in disease severity but a minority of them may progress to fibrosis/cirrhosis or liver cancer without self-awareness. To identify eligible cases for antiviral therapy, screening out chronic carriers, sensible monitoring of the disease status, and communication with the child and the parents about the cost and benefit of antiviral therapy is essential.

    Understanding the natural history of chronic hepatitis B virus infection and the indications, risks, and benefits of current antiviral therapy are critical in decision-making on who and when to treat.

    Current antiviral therapy cannot cure chronic HBV infection. Instead, the goal of anti-HBV therapy is to prevent disease progression to liver failure, cirrhosis or hepatocellular carcinoma.

    Interferon or pegylated interferon is the first-line therapy in chronic hepatitis B children in the immune active phase with high viral load (>20,000IU/mL). The pros are a finite course and no resistance; and the cons are parenteral administration, frequent adverse events, and contraindication in decompensated diseases. The efficacy of one-year therapy is up to 30% in terms of HBeAg seroconversion.

    High genetic barrier nucleos(t)ide analogs (Entecavir and Tenofovir) are first-line oral antivirals for the licensed ages in children. They are well-tolerated and highly potent in viral suppression, but it takes several years to achieve up to 50% HBeAg seroconversion. Relapse rates are high after cessation of therapy. When to stop is a challenging issue to weigh between viral reactivation or host immune clearance to take place.

    Whether the carrier children are managed with or without antivirals, lifetime monitoring, cancer surveillance and prompt intervention are key to prevent poor consequences of advanced diseases or liver cancer.

    Novel therapeutics to target different facets of HBV lifecycle or to enhance HBV-specific host immunity are undertaken to achieve a functional cure or eventually a cure.

StephenW

儿童乙型肝炎管理的最新进展
赖明伟＆张美慧
于2019年8月6日接收，于2019年10月25日接受，在线接受作者版本：2019年10月30日，在线发布：2019年11月11日

下载引文https://doi.org/10.1080/17474124.2019.1686975 CrossMark徽标CrossMark


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抽象

简介：通用婴儿乙型肝炎病毒（HBV）疫苗接种计划已减少了接种疫苗的年轻一代的HBV感染。慢性感染儿童的管理仍然面临挑战，涉及高病毒载量和大多数轻度疾病，但晚期疾病的比例不可忽略，抗病毒药的长期作用。但是，随着更有效的抗病毒药物被批准用于儿科患者，在合格患者中尽早开始抗病毒药物可能会有益于他们的结果。这项审查旨在更新目前儿童慢性乙型肝炎的管理。

涵盖领域：本综述涵盖了慢性HBV感染的自然史，过去到现在儿童的慢性乙型肝炎的治疗，当前关于儿童慢性乙型肝炎的治疗的共识，停止口服抗病毒药的争议以及对乙肝的治疗特殊人群，例如怀孕和合并感染。

专家意见：在无禁忌症的情况下，建议对3岁以上免疫活跃的儿童使用聚乙二醇干扰素。对于那些不能耐受，代偿失调或偏爱口服治疗的患者，可以应用一线Nucleos（t）ide类似物（NUC），恩替卡韦或替诺福韦。对于免疫耐受或无活性的载体，密切监视至关重要。什么时候停止NUC和治疗HBV的新疗法有待进一步研究。
关键词：核苷类似物，聚乙二醇化干扰素，HBeAg血清转化，HBsAg丢失，再活化，肝纤维化，免疫耐受，免疫清除，HBeAg阴性肝炎
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文章重点

大多数慢性HBV感染儿童的病情轻重，但其中少数人可能会发展为纤维化/肝硬化或肝癌而没有自我意识。为了确定合适的抗病毒治疗病例，筛选出慢性携带者，合理监测疾病状况，并与孩子和父母就抗病毒治疗的成本和收益进行沟通至关重要。

了解慢性乙型肝炎病毒感染的自然历史以及当前抗病毒治疗的适应症，风险和益处对于决定何时及何时治疗至关重要。

当前的抗病毒治疗无法治愈慢性HBV感染。相反，抗HBV治疗的目标是防止疾病发展为肝衰竭，肝硬化或肝细胞癌。

干扰素或聚乙二醇化干扰素是慢性乙型肝炎儿童处于免疫活跃期且病毒载量高（> 20,000 IU / mL）的一线治疗。优点是有限的过程，没有阻力。缺点是胃肠外给药，频繁的不良事件和失代偿性疾病的禁忌症。就HBeAg血清转化而言，一年治疗的有效性高达30％。

高遗传屏障核苷（核苷酸）类似物（恩替卡韦和替诺福韦）是儿童许可年龄的一线口服抗病毒药物。它们具有良好的耐受性，并且在病毒抑制方面非常有效，但是要达到高达50％的HBeAg血清转化率需要花费数年的时间。停止治疗后复发率很高。何时停止是权衡病毒重新激活或宿主免疫清除之间发生的挑战性问题。

携带或不携带抗病毒药物对携带儿童进行管理，对他们的终生监测，癌症监测和及时干预是预防晚期疾病或肝癌不良后果的关键。

采取针对HBV生命周期不同方面或增强HBV特异性宿主免疫力的新型疗法来实现功能性治愈或最终治愈。