恩替卡韦和聚乙二醇干扰素α-2a成人HBeAg阳性免疫耐受慢性乙

StephenW

Hepatology. 2018 Dec 14. doi: 10.1002/hep.30417. [Epub ahead of print]
Entecavir and peginterferon alfa-2a in adults with HBeAg-positive immune tolerant chronic hepatitis B virus infection.
Feld JJ1, Terrault NA2, Lin HS3, Belle SH3, Chung RT4, Tsai N5, Khalili M2, Perrillo R6, Cooper SL7, Ghany MG8, Janssen HLA1, Lok AS9; Hepatitis B Research Network (HBRN).
Author information

1
    Toronto Centre for Liver Disease, University of Toronto.
2
    University of California San Francisco.
3
    Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA.
4
    Massachusetts General Hospital, Harvard University.
5
    University of Hawaii.
6
    Baylor University Medical Center.
7
    San Francisco Center for Liver Disease, California Pacific Medical Centre, San Francisco, CA.
8
    Liver Diseases Branch, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health.
9
    University of Michigan.

Abstract
BACKGROUND/AIM:

Monotherapy with interferon or nucleoside analog is generally not recommended during the immune tolerant (IT) phase of chronic hepatitis B virus (HBV) infection. Recognition that high HBV DNA levels are associated with hepatocellular carcinoma has increased interest in treating HBV in the IT phase. Small pediatric studies reported efficacy with combination nucleoside analog and interferon therapy.
AIM:

To evaluate the safety and efficacy of the combination of entecavir and peginterferon in adults in the IT phase of chronic HBV infection.
METHODS:

HBeAg-positive adults with HBV DNA>107 IU/mL and ALT≤1.5x ULN: (M≤45, F≤30 U/L) received entecavir 0.5 mg daily for 8 weeks followed by addition of peginterferon alfa-2a 180 μg/week to entecavir for an additional 40 weeks. The primary endpoint was HBeAg loss and HBV DNA≤1000 IU/mL 48 weeks post-end-of-treatment (EOT).
RESULTS:

Among 28 participants from 11 sites, median age was 37.2 (range 22-61) years, 54% were male and 96% were Asian. Nearly all were infected with genotype C (64%) or B (32%). Median baseline HBV DNA was 8.2 log10 IU/mL and ALT 0.9xULN. While one (4%) participant cleared HBeAg, none met the primary endpoint of both HBeAg loss AND HBV DNA ≤1,000 IU/mL 48 weeks post-EOT. ALT elevations >5xULN occurred in 8 (29%) participants, none associated with icterus. 48 weeks post-treatment, HBV DNA rebounded to baseline levels in all participants including the participant who lost HBeAg, and ALT values returned to near-baseline levels in all but 4 participants.
CONCLUSION:

A lead-in strategy of 8 weeks of entecavir followed by combination peginterferon and entecavir therapy for 40 weeks had limited efficacy in adults in the IT phase of chronic HBV infection and cannot be recommended. This article is protected by copyright. All rights reserved.

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

HBV ; antiviral therapy; entecavir; immunetolerant; peginterferon

PMID:
    30549279
DOI:
    10.1002/hep.30417

StephenW

肝病。 2018年12月14日doi：10.1002 / hep.30417。 [提前打印]
恩替卡韦和聚乙二醇干扰素α-2a成人HBeAg阳性免疫耐受慢性乙型肝炎病毒感染。
Feld JJ1，Terrault NA2，Lin HS3，Belle SH3，Chung RT4，Tsai N5，Khalili M2，Perrillo R6，Cooper SL7，Ghany MG8，Janssen HLA1，Lok AS9;乙型肝炎研究网络（HBRN）。
作者信息

1
    多伦多大学多伦多肝病中心。
2
    加州大学旧金山分校。
3
    宾夕法尼亚州匹兹堡匹兹堡大学公共卫生研究生院。
4
    哈佛大学马萨诸塞州综合医院。
五
    夏威夷大学。
6
    贝勒大学医学中心。
7
    旧金山肝病中心，加州太平洋医疗中心，旧金山，加利福尼亚州。
8
    美国国立卫生研究院国家糖尿病与消化和肾脏疾病研究所肝病科。
9
    密歇根大学。

抽象
背景/目的：

在慢性乙型肝炎病毒（HBV）感染的免疫耐受（IT）阶段，通常不推荐使用干扰素或核苷类似物的单一疗法。认识到高HBV DNA水平与肝细胞癌相关，这增加了对IT阶段治疗HBV的兴趣。小型儿科研究报道了联合核苷类似物和干扰素治疗的疗效。
目标：

评估恩替卡韦和聚乙二醇干扰素联合治疗慢性HBV感染IT期成人的安全性和有效性。
方法：

HBV DNA> 107 IU / mL且ALT≤1.5xULN：（M≤45，F≤30U/ L）的HBeAg阳性成人每天接受恩替卡韦0.5 mg，持续8周，然后加入peginterferon alfa-2a180μg/一周到恩替卡韦再服用40周。主要终点是HBeAg消失，HBVDNA≤1000IU/ mL，治疗结束后48周（EOT）。
结果：

来自11个地点的28名参与者中，年龄中位数为37.2（范围22-61）年，54％为男性，96％为亚洲人。几乎所有人都感染了基因型C（64％）或B（32％）。中位基线HBV DNA为8.2 log10 IU / mL和ALT 0.9xULN。当一名（4％）参与者清除HBeAg时，没有人在EOT后48周达到HBeAg丢失和HBVDNA≤1,000IU/ mL的主要终点。 ALT升高> 5xULN发生在8名（29％）参与者中，没有与黄疸相关。治疗后48周，HBV DNA在所有参与者中反弹至基线水平，包括失去HBeAg的参与者，并且除4名参与者外，所有参与者的ALT值均恢复至接近基线水平。
结论：

8周恩替卡韦的引入策略，接着聚乙二醇干扰素和恩替卡韦联合治疗40周，对慢性HBV感染的IT阶段成人的疗效有限，不能推荐。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：

HBV;抗病毒治疗;恩替卡韦; immunetolerant;聚乙二醇干扰素

结论：
    30549279
DOI：
    10.1002 / hep.30417