恩替卡韦/聚乙二醇干扰素α-2a联合治疗儿童HBeAg阳性免疫耐

StephenW

Hepatology. 2018 Oct 15. doi: 10.1002/hep.30312. [Epub ahead of print]
Combination of entecavir/ peginterferon alfa-2a in children with HBeAg-positive immune tolerant chronic hepatitis B virus infection.
Rosenthal P1, Ling SC2, Belle SH3, Murray KF4, Rodriguez-Baez N5, Schwarzenberg SJ6, Teckman J7, Lin HS3, Schwarz KB8; Hepatitis B Research Network (HBRN).
Author information
Abstract

The optimal management strategy for children with immune-tolerant chronic hepatitis B virus (HBV) infection remains unknown. The purpose of this clinical trial was to determine the safety and efficacy of therapy with entecavir and peginterferon in a group of children in the immune-tolerant phase of HBV infection. Children with immune-tolerant features of chronic hepatitis B received entecavir once daily in a dose of 0.015 mg/kg (0.5 mg maximum) for 48 weeks; peginterferon alfa-2a (180 μg/1.73m2 subcutaneously) once weekly was added at the end of week 8 and continued until week 48. The primary endpoint was lack of detectable HBeAg with HBV DNA levels ≤1,000 IU/mL 48 weeks after stopping therapy. Sixty children (75% female), median age 10.9 (range 3.4-17.9) years, were enrolled. All were positive for HBsAg and HBeAg and had high levels of HBV DNA with normal or minimally elevated levels of alanine aminotransferase (ALT). Fifty-five children completed the entire 48-week course of therapy. At 48 weeks after treatment ended (week 96), two children (3%) achieved the primary endpoint and were also HBsAg negative and anti-HBs positive. One child was HBeAg positive but HBsAg negative at week 60; another was HBeAg negative but HBsAg positive at week 72 which were their last clinic visits. In the remaining children, serum ALT and HBV DNA levels at week 96 were similar to baseline. Thirty-seven children experienced adverse events (AE) and one had a serious AE.
CONCLUSION:

The combination of entecavir and peginterferon for up to 48 weeks rarely led to loss of HBeAg with sustained suppression of HBV DNA levels in children in the immune-tolerant phase of HBV infection, and treatment was associated with frequent AEs. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.
KEYWORDS:

HBeAg seroconversion; adverse events; antiviral trial; pediatrics; treatment; viral load

PMID:
    30318613
DOI:
    10.1002/hep.30312

StephenW

肝病。 2018年10月15日doi：10.1002 / hep.30312。 [提前打印]
恩替卡韦/聚乙二醇干扰素α-2a联合治疗儿童HBeAg阳性免疫耐受慢性乙型肝炎病毒感染。
Rosenthal P1，Ling SC2，Belle SH3，Murray KF4，Rodriguez-Baez N5，Schwarzenberg SJ6，Teckman J7，Lin HS3，Schwarz KB8;乙型肝炎研究网络（HBRN）。
作者信息
抽象

对免疫耐受性慢性乙型肝炎病毒（HBV）感染儿童的最佳管理策略仍然未知。该临床试验的目的是确定恩替卡韦和聚乙二醇干扰素治疗一组HBV感染免疫耐受期儿童的安全性和有效性。患有慢性乙型肝炎免疫耐受特征的儿童每天服用恩替卡韦，剂量为0.015 mg / kg（最大0.5 mg），持续48周;聚乙二醇干扰素α-2a（皮下注射180μg/ 1.73m2）每周一次，在第8周结束时加入并持续至第48周。主要终点是缺乏可检测的HBeAg，停止治疗48周后HBV DNA水平≤1,000IU/ mL 。招募了60名儿童（75％女性），中位年龄10.9（范围3.4-17.9）岁。 HBsAg和HBeAg均为阳性，HBV DNA水平高，丙氨酸氨基转移酶（ALT）水平正常或升高。五十五名儿童完成了为期48周的整个治疗过程。在治疗结束后48周（第96周），两名儿童（3％）达到主要终点，并且HBsAg阴性和抗HBs阳性。一名儿童HBeAg阳性，但60周时HBsAg阴性;另一例是HBeAg阴性，但第72周HBsAg阳性，这是他们最后一次就诊。在剩余的儿童中，第96周的血清ALT和HBV DNA水平与基线相似。 37名儿童出现不良事件（AE），1名儿童出现严重AE。
结论：

恩替卡韦和聚乙二醇干扰素联合使用长达48周，很少导致HBeAg的丢失，HBV感染的免疫耐受期儿童HBV DNA水平持续受到抑制，且治疗与频繁的AE有关。本文受版权保护。版权所有。

本文受版权保护。版权所有。
关键词：

HBeAg血清学转换;不良事件;抗病毒试验;儿科;治疗;病毒载量

结论：
    30318613
DOI：
    10.1002 / hep.30312