乙型肝炎病毒包膜抗原阳性慢性乙型肝炎患者的PEG化干扰素Al

StephenW

J Infect Dis. 2017 Mar 17. doi: 10.1093/infdis/jix024. [Epub ahead of print]
Pegylated Interferon Alfa-2b Add-on Treatment in Hepatitis B Virus Envelope Antigen-Positive Chronic Hepatitis B Patients Treated with Nucleos(t)ide Analogue: A Randomized, Controlled Trial (PEGON).
Chi H1, Hansen BE1, Guo S2, Zhang NP3, Qi X4, Chen L4, Guo Q2, Arends P1, Wang JY3, Verhey E1, de Knegt RJ1, Xie Q2, Janssen HL1,5.
Author information

1    Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands.
2    Department of Infectious Diseases, Ruijin Hospital, Jiaotong University, Shanghai, China, and.
3    Department of Gastroenterology and Hepatology, Zhongshan Hospital, Shanghai, China, and.
4    Department of Hepatitis Disease, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China; and.
5    Toronto Centre for Liver Disease, University Health Network, Toronto General Hospital, University of Toronto, Canada.

Abstract
Background.:

We studied whether 48 weeks of pegylated interferon alfa-2b (peginterferon) add-on therapy increases serological response in hepatitis B virus (HBV) envelope antigen (HBeAg)-positive patients receiving nucleos(t)ide analogue (NA) therapy, compared with continued NA monotherapy.
Methods.:

This randomized trial included HBeAg-positive patients with compensated liver disease who were treated with entecavir/tenofovir for >12 months and had an HBV DNA load of <2000 IU/mL. Patients were randomly assigned in a 1:1 ratio to 48 weeks of peginterferon add-on therapy (n = 39) or continued NA monotherapy (n = 38). Response (defined as HBeAg seroconversion with an HBV DNA load of <200 IU/mL) was assessed at week 48, with responders discontinuing NA therapy at week 72.
Results.:

The primary end point (response at week 96) was achieved in 18% of patients who were assigned peginterferon add-on therapy versus 8% of patients assigned NA monotherapy (P = .31). Among 58 interferon-naive patients, add-on therapy led to a greater frequency of HBeAg seroconversion (30% vs 7%; P = .034) and response (26% vs 7%; P = .068) at week 96, compared with monotherapy. Among 8 responders at week 48 who discontinued NA therapy at week 72, 6 patients (75%) maintained a response until week 96 (4 of 6 [67%] in the add-on therapy group vs 2 of 2 [100%] in the monotherapy group; P = 1.00). Adverse events were mainly related to peginterferon.
Conclusion.:

The primary end point was negative, but peginterferon add-on therapy appeared to result in a greater frequency of HBeAg seroconversion, compared with NA monotherapy, in interferon-naive patients receiving NA therapy.
Clinical Trials Registration.:

NCT01532843.
KEYWORDS:

Antiviral therapy; HBeAg seroconversion; combination therapy; interferon naive.

PMID:
    28329061
DOI:
    10.1093/infdis/jix024

StephenW

J Infect Dis 2017年3月17日。doi：10.1093 / infdis / jix024。 [提前印刷]
乙型肝炎病毒包膜抗原阳性慢性乙型肝炎患者的PEG化干扰素Alfa-2b附加治疗用Nucleos（t）ide处理模拟：随机对照试验（PEGON）。
Chi H1，Hansen BE1，Guo S2，Zhang NP3，Qi X4，Chen L4，Guo Q2，Arends P1，Wang JY3，Verhey E1，de Knegt RJ1，Xie Q2，Janssen HL1,5。
作者信息

1荷兰鹿特丹鹿特丹伊拉斯姆斯MC大学医学中心消化内科和肝脏病学系。
2中国上海交通大学瑞金医院传染病科。
3中国上海市中山医院消化内科，肝病科，
4复旦大学上海市公共卫生临床中心上海市肝炎病毒科，上海;和。
多伦多多伦多大学多伦多大学健康网络多伦多大学多伦多中心，加拿大多伦多大学多伦多综合医院多伦多中心。

抽象
背景。：

我们研究了48周的聚乙二醇化干扰素α-2b（聚乙二醇化干扰素）附加治疗是否增加了接受核苷类似物（NA）治疗的乙型肝炎病毒（HBV）包膜抗原（HBeAg）阳性患者的血清学反应，与继续NA单药治疗。
方法。：

这项随机试验包括HBeAg阳性患者，补充肝脏疾病，恩替卡韦/替诺福韦治疗> 12个月，HBV DNA负荷<2000 IU / mL。患者以1：1的比例随机分配至48周的聚乙二醇化干扰素附加治疗（n = 39）或持续NA单药治疗（n = 38）。在第48周评估响应（定义为HBV DNA负载<200IU / mL的HBeAg血清学转换），应答者在第72周停止NA治疗。
结果：

18％的受试者接受了聚乙二醇干扰素附加治疗，而接受单一治疗的患者为8％（P = .31），主要终点（第96周）。在58名干扰素初次患者中，附加治疗在第96周导致HBeAg血清学转换的频率更高（30％vs 7％; P = 0.034）和反应（26％对7％; P = 0.068），比较与单一疗法。在第48周的8名患者中，在第72周停用NA治疗的患者中，6例（75％）维持响应，直到第96周（附加治疗组6例中为6例[67％]，2例[100％]中有2例单药治疗组; P = 1.00）。不良事件主要与聚乙二醇化干扰素有关。
结论。：

主要终点为阴性，但与接受NA治疗的干扰素初次患者相比，单核苷酸治疗相比，聚乙二醇化干扰素附加治疗似乎导致HBeAg血清学转换的频率更高。
临床试验注册：

NCT01532843。
关键词：

抗病毒治疗; HBeAg血清学转换;联合治疗;干扰素天真

PMID：
    28329061
DOI：
    10.1093 / infdis / jix024