乙型肝炎病毒感染儿童免疫耐受特征的抗病毒治疗：试点开

StephenW

J Hepatol. 2018 Feb 13. pii: S0168-8278(18)30117-X. doi: 10.1016/j.jhep.2018.01.037. [Epub ahead of print]
Antiviral therapy in hepatitis B virus-infected children with immune-tolerant characters: a pilot open-lable randomized study.Zhu S1, Zhang H1, Dong Y1, Wang L1, Xu Z1, Liu W2, Gan Y1, Tang H3, Chen D1, Wang F1, Zhao P4.
Author information
1Pediatric Liver Diseases Therapy and Research Center, Beijing 302 Hospital, Beijing 100039, China.2Department of Medical Statistics, Academy of Military Medical Sciences, Beijing 100850, China.3Clinical Trial Center; Institute of Infectious Diseases; Liver Failure Therapy and Research Center, Beijing 302 Hospital, Beijing 100039, China.4Clinical Trial Center; Institute of Infectious Diseases; Liver Failure Therapy and Research Center, Beijing 302 Hospital, Beijing 100039, China. Electronic address: [email protected].

AbstractBACKGROUND & AIM: Chronic infection with hepatitis B virus (HBV) in children possesses a serious health problem worldwide. It remains unresolved how children with immune-tolerant chronic hepatitis B should be treated, who were commonly characterized by HBeAg positivity, high viral load, normal or mildly elevated ALT and no or minimal inflammation in liver histology. This trial aims to study the benefits of antiviral therapy in children with these characters.
METHODS: This is a pilot open-lable randomized controlled study. From May 2014 to April 2015, treatment-naïve chronically HBV-infected children aged 1 to 16 years who had immune-tolerant characters were recruited to this trial and randomly assigned, in a 2:1 ratio, to treatment group and control group. Patients in the treatment group were administrated with interferon-α (INF) monotherapy or consecutively received INF monotherapy, combination therapy of IFN and lamivudine (LAM), and LAM therapy alone. All patients were observed till week 96.
RESULTS: Sixty-nine patients were enrolled in the trial. 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 HBsAg at the endpoint. No LAM resistance emerged at week 96. In the control group, only 1 (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 IFN and LAM sequential combination can result in significant improvement in the rates of undetectable serum HBV DNA, HBeAg seroconversion and HBsAg loss in these children with immune-tolerant characters. Lay summary There is a paucity 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-lable randomized controlled trial on antiviral therapy in children with immune-tolerant characters.

Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

KEYWORDS: children; chronic hepatitis B; interferon; lamivudine

PMID:29452204DOI:10.1016/j.jhep.2018.01.037

StephenW

J Hepatol。 2018年2月13日。pii：S0168-8278（18）30117-X。 doi：10.1016 / j.jhep.2018.01.037。 [电子版提前打印]
乙型肝炎病毒感染儿童免疫耐受特征的抗病毒治疗：试点开放随机研究。
中国科学院遗传与发育生物学国家重点实验室，中国科学院遗传与发育生物学研究所，北京100080
作者信息

1
    北京302医院儿科肝病治疗研究中心，北京100039
2
    军事医学科学院医学统计司，北京100850
3
    临床试验中心;传染病研究所;北京302医院肝衰竭治疗研究中心，北京100039
4
    临床试验中心;传染病研究所;北京302医院肝衰竭治疗研究中心，北京100039电子地址：[email protected]。

抽象
背景与目的：

儿童乙型肝炎病毒（HBV）慢性感染在世界范围内具有严重的健康问题。如何治疗患有免疫耐受性慢性乙型肝炎的儿童，他们通常具有HBeAg阳性，病毒载量高，ALT正常或轻度升高，肝组织学无炎症或轻度炎症等特征，这一点尚未得到解决。该试验旨在研究抗病毒治疗对患有这些特征的儿童的益处。
方法：

这是一项试点开放随机对照研究。从2014年5月至2015年4月，初治的慢性HBV感染儿童1至16岁具有免疫耐受特征的患者被纳入该试验，并以2：1的比例随机分配至治疗组和对照组。治疗组患者给予干扰素-α（INF）单药治疗或连续接受INF单药治疗，联合应用IFN和拉米夫定（LAM），单独应用LAM治疗。直到第96周，观察所有患者。
结果：

试验中有69名患者入选。在基线时，整个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是一致的。在治疗组46例患者中，73.91％血清HBV DNA检测不到，32.61％达到HBeAg血清学转换，21.74％在终点时丢失了HBsAg。对照组仅有1例（4.35％）患者发生自发性HBeAg血清学转换，并且在观察期间检测不到血清HBV DNA，而且没有发现HBsAg清除。对于所有患者，未观察到严重不良事件。
结论：

采用IFN和LAM序列联合治疗的抗病毒治疗可以显着改善这些具有免疫耐受特征的儿童血清HBV DNA检测率，HBeAg血清学转换率和HBsAg消失率。总结关于治疗免疫耐受性慢性乙型肝炎（CHB）的资料很少。如何治疗患有免疫耐受性CHB的儿童仍未得到解决。本文报告了免疫耐受性儿童抗病毒治疗试验开放随机对照试验的结果。

版权所有©2018年欧洲肝脏研究协会。由Elsevier B.V.出版。保留所有权利。
关键词：

儿童;慢性乙型肝炎;干扰素;拉米夫定

结论：
    29452204
DOI：
    10.1016 / j.jhep.2018.01.037