早期抗病毒治疗可减少婴儿乙型肝炎感染中的HBsAg

StephenW

Early Antiviral Therapy Reduces HBsAg in Infantile Hepatitis B Infection
Gary Rothbard, MD, MS


Infants diagnosed with hepatitis B virus (HBV) infection who were treated with antiviral therapy within the first 12 months of life demonstrated marked rapid HBV surface antigen (HBsAg) loss when compared with those left untreated during the first year, according to a report published in the Journal of Hepatology.

Despite the morbidity associated with chronicity, there has been little research into seroconversion with antiviral therapy administered to patients with infantile HBV, and no specific guidelines regarding treatment of this population have been established. Investigators sought to evaluate the safety and efficacy of early antiviral treatment for infants with HBV, in a first of its kind study.


Between 2010 and 2017, a prospective cohort study enrolled consecutive Chinese infants <1 year of age who were infected with HBV and who had received postnatal immunoprophylaxis but still had high viral loads, presence of serum HBsAg, and persistent alanine aminotransferase elevation equal to or more than twice the upper limit of normal (40 U/L). A total of 29 infants were divided into 2 groups based on parental treatment decisions: group I (n=18; 61.1% male; median age at diagnosis, 6 months) comprised those treated with lamivudine (4 mg/kg daily) within the first year, while group II (n=11; 90.9% male; median age at diagnosis, 7 months) consisted of patients who did not receive any antiviral therapy in the first year and were treated with interferon-α (3-5 MU/m2 every other day) after 1 year.

All participants were monitored every 3 months using a viral profile that included HBsAg quantification, with the primary outcome being the rate of loss of serum HBsAg after 12 months of therapy. Statistical differences between groups were assessed using the log-rank test.

Baseline characteristics were similar in the 2 groups, without significant differences. Cumulative serum HBsAg loss rates in group I were 39%, 67%, 78%, and 83% at 3, 6, 9, and 12 months of treatment, respectively. In group II, at the same therapeutic time points, the respective rates of cumulative serum HBsAg loss were 18%, 27%, 27%, and 36%. At 12 months, there was a significant difference between the groups in terms of HBsAg loss rates (P =.0169). In longer-term follow-up past 12 months, significant group differences in loss rates remained, with group I seeing greater and more rapid HBsAg loss over time (P =.0023).

No group II infants showed spontaneous HBsAg loss within the first year of life prior to treatment; 9 group I infants had reached this benchmark at 12 months of treatment, representing a significant difference between groups (P =.0052). After 12 months of therapy, all study participants had achieved undetectable viral loads, regardless of group.

The most frequent adverse event was fever, and there were no serious Adverse events reported during the study. There was no evidence of lamivudine resistance or virologic breakthrough during the study.

Study strengths included a well-characterized cohort. Study limitations included a small sample size.

“Therefore … antiviral treatments in HBV-infected infants with elevated [alanine aminotransferase] levels and high viral load should be considered,” noted the authors, adding, “Timing of treatment is a critical decision in order to maximize therapeutic benefit.” They recommended that future research involve larger trials aimed at validating their findings.

Funding and Conflicts of Interest Disclosures:

This study was funded by Beijing Municipal Science and Technology Commission (No. Z181100001718035) and China National Natural Science Foundation (No. 81501652).

There were no conflicts of interest declared.

Reference

Zhu S, Dong Y, Wang L, Liu W, Zhao P. Early initiation of antiviral therapy contributes to a rapid and significant loss of serum HBsAg in infantile-onset hepatitis B [published online June 19, 2019]. J Hepatol. doi:10.1016/j.jhep.2019.06.009

StephenW

早期抗病毒治疗可减少婴儿乙型肝炎感染中的HBsAg
Gary Rothbard，医学博士，硕士


根据发表于第一年的报告，与未接受治疗的患者相比，在出生后头12个月内接受抗病毒治疗的乙型肝炎病毒（HBV）感染患儿的HBV表面抗原（HBsAg）明显快速下降。肝脏病学杂志。

尽管与慢性病相关的发病率很少，但对婴儿HBV患者进行抗病毒治疗的血清学转换研究很少，并且没有建立关于该人群治疗的具体指导方针。研究人员首次尝试评估早期抗病毒治疗对HBV婴儿的安全性和有效性。


2010年至2017年间，一项前瞻性队列研究纳入了连续1岁以下的婴儿，他们感染了HBV，并且接受了产后免疫预防但仍然具有高病毒载量，血清HBsAg存在，以及持续的丙氨酸氨基转移酶升高等于或大于等超过正常上限的两倍（40 U / L）。根据父母的治疗决定，共有29名婴儿被分为2组：第一组（n = 18; 61.1％的男性;诊断时的中位年龄，6个月）包括在第一组中使用拉米夫定（每日4 mg / kg）治疗的婴儿年，而第II组（n = 11; 90.9％的男性;诊断时的中位年龄，7个月）包括第一年未接受任何抗病毒治疗并接受干扰素-α治疗的患者（3-5 MU / m2）每隔一天）1年后。

使用包括HBsAg定量的病毒谱每3个月监测所有参与者，主要结果是治疗12个月后血清HBsAg的丢失率。使用对数秩检验评估组间的统计学差异。

两组的基线特征相似，没有显着差异。治疗3,6,9和12个月时，I组累积血清HBsAg丢失率分别为39％，67％，78％和83％。在组II中，在相同的治疗时间点，累积血清HBsAg损失的相应比率分别为18％，27％，27％和36％。在12个月时，各组之间在HBsAg丢失率方面存在显着差异（P = .0169）。在过去12个月的长期随访中，损失率的显着组间差异仍然存在，第I组随着时间的推移出现更大和更快的HBsAg损失（P = .0023）。

没有II组婴儿在治疗前的第一年内出现自发性HBsAg消失; 9个I组婴儿在治疗12个月时达到该基准，代表组间的显着差异（P = .0052）。治疗12个月后，所有研究参与者均无法检测到病毒载量，无论其如何。

最常见的不良事件是发烧，并且在研究期间没有报告严重的不良事件。在研究期间没有拉米夫定耐药性或病毒学突破的证据。

研究优势包括一个特征明确的队列。研究限制包括样本量小。

“因此......应考虑在HBV感染的婴儿中使用[丙氨酸氨基转移酶]水平升高和病毒载量高的抗病毒治疗，”作者指出，“为了最大限度地提高治疗效益，治疗时机是一个关键决定。”他们建议未来的研究涉及更大的试验，旨在验证他们的发现。

资金和利益冲突披露：

本研究由北京市科学技术委员会（No.Z181100001718035）和中国国家自然科学基金（No. 81501652）资助。

没有宣布利益冲突。

参考

Zhu S，Dong Y，Wang L，Liu W，Zhao P.早期开始抗病毒治疗有助于婴儿乙型肝炎患者血清HBsAg的快速和显着丧失[在线发表于2019年6月19日]。 J Hepatol。 DOI：10.1016 / j.jhep.2019.06.009