Antiviral therapy in hepatitis B virus-infected children with immune-tolerant characteristics: A pilot open-label randomized study
Antiviral therapy in hepatitis B virus-infected children with immune-tolerant characteristics: A pilot open-label randomized study
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具有免疫耐受特征的乙型肝炎病毒感染儿童的抗病毒治疗：一项试点开放标签随机研究
DOI：
10.1016/j.jhep.2018.01.037
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发表时间：
2018-06-01
影响因子：
25.7
通讯作者：
Zhao, Pan
中科院分区：
文献类型：
--
作者：
Zhu, Shishu;Zhang, Hongfei;Zhao, Pan
背景与目的：儿童慢性B型肝炎病毒（HBV）感染是一个严重的全球性健康问题。如何治疗免疫耐受的慢性B型肝炎感染的儿童，通常以B e抗原（HBeAg）阳性、高病毒载量、正常或轻度升高的丙氨酸氨基转移酶和肝脏组织学无炎症或炎症轻微为特征，仍然没有解决。本试验旨在研究抗病毒治疗对具有这些特征的儿童的益处。方法：这是一项开放标签的随机对照试验。从2014年5月至2015年4月，69名年龄在1至16岁之间，具有免疫耐受特征的未经治疗的慢性HBV感染儿童被招募到本试验中，并以2：1的比例随机分配到治疗组和对照组。治疗组患者接受干扰素-α（IFN）单药治疗或连续接受IFN单药治疗、IFN与拉米夫定（LAM）联合治疗以及LAM单药治疗。结果：治疗组和对照组的流行病学、生化、血清学、病毒学和组织学指标基本一致。治疗组46例患者中，73.91%血清HBV DNA转阴，32.61% HBeAg血清转换，21.74% HBsAg转阴。在第96周没有出现LAM耐药性。在对照组中，只有1例（4.35%）患者在观察期间发生自发HBeAg血清转换，血清HBV DNA未检测到，而且没有人发生HBsAg清除。对于所有患者，没有严重的不良事件observed.Conclusion：抗病毒治疗与IFN和LAM的序贯组合导致了一个显着的改善率不可检测的血清HBV DNA，HBeAg血清转换和HBsAg的损失在儿童慢性HBV感染和免疫耐受的特点。奠定总结：有一个缺乏有关治疗免疫耐受的慢性乙型肝炎B（CH B）的数据。如何治疗免疫耐受性CHB儿童仍然没有解决。本文报道了一项在具有免疫耐受特征的儿童中进行抗病毒治疗的先导性开放标签随机对照试验的结果。这表明干扰素-α和拉米夫定的序贯组合是有益的。(C)2018年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
Background & Aim: Chronic infection with hepatitis B virus (HBV) in children is a serious health problem worldwide. How to treat children with immune-tolerant chronic hepatitis B infection, commonly characterized by hepatitis B e antigen (HBeAg) positivity, high viral load, normal or mildly elevated alanine aminotransferase and no or minimal inflammation in liver histology, remains unresolved. This trial aims to study the benefits of antiviral therapy in children with these characteristics.Methods: This is a pilot open-label randomized controlled study. From May 2014 to April 2015, 69 treatment-naive chronically HBV-infected children, aged 1 to 16 years, who had immune-tolerant characteristics were recruited to this trial and randomly assigned, in a 2:1 ratio, to treatment group and control group. Patients in the treatment group received either interferon-alpha (IFN) monotherapy or consecutively received IFN monotherapy, combination therapy of IFN and lamivudine (LAM), and LAM therapy alone. All patients were observed until week 96.Results: At baseline, epidemiological, biochemical, serological, virological and histological indices were consistent across the treatment and control groups. Of the 46 patients in the treatment group, 73.91% had undetectable serum HBV DNA, 32.61% achieved HBeAg seroconversion and 21.74% lost hepatitis B surface antigen (HBsAg) at the endpoint. No LAM resistance emerged at week 96. In the control group, only one (4.35%) patient underwent spontaneous HBeAg seroconversion and had undetectable serum HBV DNA during observation, and moreover, none developed HBsAg clearance. For all patients, no serious adverse events were observed.Conclusion: Antiviral treatment with a sequential combination of IFN and LAM resulted in a significant improvement in the rates of undetectable serum HBV DNA, HBeAg seroconversion and HBsAg loss in children with chronic HBV infection and immune-tolerant characteristics.Lay summary: There is a lack of data regarding treatment of immune-tolerant chronic hepatitis B (CHB). It remains unresolved how children with immune-tolerant CHB should be treated. This paper reports the outcomes from a pilot open-label randomized controlled trial on antiviral therapy in children with immune-tolerant characteristics. It shows that a sequential combination of interferon-alpha and lamivudine was beneficial. (C) 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.