聚乙二醇干扰素-α治疗的HBeAg阳性患者的STAT4变异与慢性HBV感

StephenW

Clin Gastroenterol Hepatol. 2020 Jan;18(1):196-204.e8. doi: 10.1016/j.cgh.2019.04.044. Epub 2019 Apr 28.
Variants in STAT4 Associated With Cure of Chronic HBV Infection in HBeAg-positive Patients Treated With Pegylated Interferon-alpha.
Chen H1, Sun J1, Zhou B1, Xie Q2, Liang X1, Fan R1, Conran C3, Xu J4, Ji Y5, Zhang X6, Sun L7, Jia J8, Wang G9, Hou J10, Jiang DK11.
Author information

1
    State Key Laboratory of Organ Failure Research, Guangdong Key Laboratory of Viral Hepatitis Research, Institutes of Liver Diseases Research of Guangdong Province, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, GuangZhou, China.
2
    Department of Infectious Diseases, Rui Jin Hospital Shanghai Jiao Tong University School of Medicine, Shanghai, China.
3
    University of Illinois College of Medicine, Chicago, Illinois.
4
    Program for Personalized Cancer Care, NorthShore University HealthSystem, Evanston, Illinois.
5
    Department of Public Health Sciences, University of Chicago, Chicago, Illinois.
6
    Department of Infectious Disease, Institute of Infectious and Respiratory Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
7
    Xiamen Amoytop Biotech Co Ltd, Xiamen, China.
8
    Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
9
    Department of Infectious Diseases, Center for Liver Diseases, Peking University First Hospital, Beijing, China; Peking University International Hospital, Beijing, China; The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China. Electronic address: [email protected].
10
    State Key Laboratory of Organ Failure Research, Guangdong Key Laboratory of Viral Hepatitis Research, Institutes of Liver Diseases Research of Guangdong Province, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, GuangZhou, China. Electronic address: [email protected].
11
    State Key Laboratory of Organ Failure Research, Guangdong Key Laboratory of Viral Hepatitis Research, Institutes of Liver Diseases Research of Guangdong Province, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, GuangZhou, China. Electronic address: [email protected].

Abstract
BACKGROUND & AIMS:

Variants in STAT4 (rs7574865) have been associated with seroconversion to hepatitis B e antigen (HBeAg) and reduction in levels of hepatitis B virus (HBV) DNA in patients with chronic infection treated with interferon alpha (IFNA). We evaluated the associations among rs7574865, loss of HB surface antigen (HBsAg, a marker of functional cure of HBV infection), and response to treatment with pegylated IFNA (PegIFN) or nucleos(t)ide analogues (NUCs) in HBeAg-positive patients with chronic HBV infection.
METHODS:

We performed a retrospective analysis of 1823 HBeAg-positive patients with chronic HBV infection (954 patients treated with PegIFN and 869 patients treated with NUCs) included in 4 phase-4 multicenter randomized controlled trials. The Cochran-Armitage trend test was used to evaluate the association of rs7574865 genotype with combined response (CR, defined as HBeAg seroconversion and HBV DNA level <2000 IU/mL) and loss of HBsAg at week 72, for patients given PegIFN, or week 104, for patients given NUCs.
RESULTS:

We found a significant association between rs7574865 genotype and CR (P = .004) and loss of HBsAg (P = .037) in patients treated with PegIFN. In patients with HBV genotype B infection, 43.6% of those with rs7574865 TT achieved a CR, compared to patients with rs7574865 GG (20.5%), and 7.7% had loss of HBsAg, compared to 1.9% of patients with rs7574865 GG. However, in patients treated with NUCs, we found no association of rs7574865 genotype with CR (P = .811) or loss of HBsAg (P=.439).
CONCLUSIONS:

In a retrospective analysis of data from 4 clinical trials, we found rs7574865 in STAT4 to be associated with functional cure of chronic HBV infection by PegIFN treatment, but not NUCs treatment, in HBeAg-positive patients with HBV genotype B infection.

Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.
KEYWORDS:

Drug; EFFORT; EXCEL; EXPLORE Trial

PMID:
    31042581
DOI:
    10.1016/j.cgh.2019.04.044

StephenW

Castro Gastroenterol Hepatol。 2020年1月； 18（1）：196-204.e8。土井（Doi）：10.1016 / j.cgh.2019.04.044。 EPUB 2019年4月28日。
聚乙二醇干扰素-α治疗的HBeAg阳性患者的STAT4变异与慢性HBV感染的治愈相关。
陈H1，孙J1，周B1，谢Q2，梁X1，范R1，柯南C3，徐J4，吉Y5，张X6，孙L7，贾J8，王G9，侯J10，姜DK11。
作者信息

1个
南方医科大学附属南方医院传染病与肝病科，器官衰竭研究国家重点实验室，广东省肝病研究所，广东省病毒性肝炎研究重点实验室，广东广州。
2
上海交通大学医学院附属瑞金医院传染病科，上海
3
伊利诺伊大学医学院，伊利诺伊州芝加哥。
4
伊利诺伊州埃文斯顿北肖尔大学医疗系统个性化癌症护理计划。
5
伊利诺伊州芝加哥大学芝加哥大学公共卫生科学系。
6
上海交通大学医学院附属瑞金医院传染病与呼吸疾病研究所传染病科，上海
7
厦门厦门厦门生物科技有限公司，中国厦门。
8
首都医科大学附属北京友谊医院肝脏研究中心，北京
9
北京大学第一医院肝病中心传染病科，北京；北京大学国际医院，北京；浙江大学传染病诊断与治疗合作创新中心，杭州，中国。电子地址：[email protected]。
10
南方医科大学附属南方医院传染病与肝病科，器官衰竭研究国家重点实验室，广东省肝病研究所，广东省病毒性肝炎研究重点实验室，广东广州。电子地址：jlhousmu @ 163 .com。
11
南方医科大学附属南方医院传染病与肝病科，器官衰竭研究国家重点实验室，广东省肝病研究所，广东省病毒性肝炎研究重点实验室，广东广州。电子地址：dekejiang @ 163 .com。

抽象
背景与目的：

STAT4的变异（rs7574865）与血清慢性转化为乙型肝炎e抗原（HBeAg）和乙型肝炎干扰素（IFNA）治疗的慢性感染患者的乙型肝炎病毒（HBV）DNA水平降低有关。我们评估了rs7574865，HBeAg阳性患者中HB表面抗原（HBsAg，HBV感染的功能性治愈标志物）的丢失以及对聚乙二醇化IFNA（PegIFN）或核苷酸（t）ide类似物（NUCs）的治疗反应之间的相关性慢性HBV感染。
方法：

我们对4项4期多中心随机对照试验中的1823例慢性HBV感染HBeAg阳性患者（954例接受PegIFN治疗的患者和869例接受NUC治疗的患者）进行了回顾性分析。 Cochran-Armitage趋势测试用于评估在第72周接受PegIFN或治疗的患者，rs7574865基因型与联合反应（CR，定义为HBeAg血清转化和HBV DNA水平<2000 IU / mL）和HBsAg丧失之间的关联。 104，给予NUC的患者。
结果：

我们发现在接受PegIFN治疗的患者中，rs7574865基因型与CR（P = .004）与HBsAg丢失（P = .037）之间存在显着相关性。在HBV基因型B感染的患者中，与rs7574865 GG患者（20.5％）相比，rs7574865 TT患者中有43.6％达到了CR，而rs7574865 GG患者中有1.9％达到了HBsAg丢失。但是，在接受NUC治疗的患者中，我们发现rs7574865基因型与CR（P = .811）或HBsAg丢失（P = .439）没有关联。
结论：

在对来自4个临床试验的数据进行的回顾性分析中，我们发现STAT4中的rs7574865与通过PegIFN治疗而不是NUCs治疗慢性HBV感染的功能性治愈有关，而对于HBeAg阳性HBV基因型B感染的患者而言。

版权所有©2020 AGA Institute。由Elsevier Inc.出版。保留所有权利。
关键字：

药物; EFFORT； EXCEL;探索试用

PMID：
31042581
DOI：
10.1016 / j.cgh.2019.04.044