免疫活性慢性乙型肝炎患者中与HBeAg血清转换延迟相关的免疫

StephenW

Antiviral Res. 2020 Jan 28:104719. doi: 10.1016/j.antiviral.2020.104719. [Epub ahead of print]
Genotyping of immune-related loci associated with delayed HBeAg seroconversion in immune-active chronic hepatitis B patients.
Liu WC1, Wu IC2, Chiu YC3, Tseng KC4, Chen CY5, Chiu HC6, Cheng PN7, Chang TT8.
Author information

1
    Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC; Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan, ROC. Electronic address: [email protected].
2
    Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC. Electronic address: [email protected].
3
    Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC. Electronic address: [email protected].
4
    Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi, Taiwan, ROC. Electronic address: [email protected].
5
    Department of Internal Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan. Electronic address: [email protected].
6
    Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC. Electronic address: [email protected].
7
    Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC. Electronic address: [email protected].
8
    Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC; Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan, ROC. Electronic address: [email protected].

Abstract

The progression of chronic hepatitis B (CHB) is associated with single-nucleotide polymorphisms (SNPs). In this study, we demonstrated the association between immune-related SNPs and delayed spontaneous HBeAg seroconversion in immune-active CHB patients. In addition, we investigated the impact of delayed spontaneous HBeAg seroconversion-related SNPs on HBeAg seroconversion within 3 years during antiviral treatment. We enrolled 332 CHB patients and genotyped 124 SNPs associated with HBV-infected clinical outcomes, including 32 interleukin-related genes, 62 HLA genes, 9 CD marker genes, 7 NK cell receptor genes, and 14 other genes, using ABI OpenArray as a platform. Comparing the immune-active CHB patients with delayed spontaneous HBeAg seroconversion (persistent HBeAg seropositivity, older than 40 years) to those with early inefficient HBeAg seroconversion (HBeAg seroconversion with high viremia, younger than 40 years), logistic analysis revealed that rs3820998 (TANK), rs2621377 (HLA-DOB), rs3130215 (HLA-DPB2), rs2255336 (KLRK1), and rs11614913 (MIR-196A2) were significantly associated with delayed spontaneous HBeAg seroconversion. Using multivariate analysis, we determined that high serum HBV DNA levels (OR = 1.66, 95% CI = 1.33-2.08), rs3820998 (CA, OR = 3.37, 95% CI = 1.24-9.12), rs2621377 (TC, OR = 4.96, 95% CI = 1.85-13.3), rs2255336 (TT, OR = 0.09, 95% CI = 0.01-0.86), and rs11614913 (TT, OR = 2.53, 95% CI = 1.05-6.11) were five independent risk factors for delayed spontaneous HBeAg seroconversion. After patients received nucleos(t)ide analogue treatment, rs3820998 heterozygous CA variant conversely became the only independent favorable factor for treatment-induced HBeAg seroconversion within 3 years (OR = 0.21, 95% CI = 0.06-0.78). These results indicate that distinct immune-related SNPs play a vital role in regulating HBeAg status in immune-active CHB patients with or without antiviral treatment.

Copyright © 2020. Published by Elsevier B.V.
KEYWORDS:

Delayed spontaneous HBeAg seroconversion; Early inefficient HBeAg seroconversion; Immune-active chronic hepatitis B; Persistent HBeAg seropositivity; Single-nucleotide polymorphism

PMID:
    32004619
DOI:
    10.1016/j.antiviral.2020.104719

StephenW

抗病毒水库。 2020年1月28日：104719。 doi：10.1016 / j.antiviral.2020.104719。 [Epub提前发行]
免疫活性慢性乙型肝炎患者中与HBeAg血清转换延迟相关的免疫相关基因座的基因分型。
Liu WC1，Wu IC2，Chiu YC3，Tseng KC4，Chen CY5，Chiu HC6，Cheng PN7，Chang TT8。
作者信息

1个
    国立成功大学附属医院内科，国立成功大学，台湾国立成功大学传染病与信号研究中心，台湾台南。电子地址：[email protected]。
2
    国立成功大学医院内科，国立成功大学医学院，台湾台南。电子地址：[email protected]。
3
    国立成功大学医院内科，国立成功大学医学院，台湾台南。电子地址：[email protected]。
4
    中华民国台湾嘉义市佛教慈济医学基金会大林慈济医院内科。电子地址：[email protected]。
5
    台湾嘉义市嘉义基督教医院迪特曼森医学基金会内科。电子地址：[email protected]。
6
    国立成功大学医学院附属内科，国立成功大学，台湾台南。电子地址：[email protected]。
7
    国立成功大学医院内科，国立成功大学医学院，台湾台南。电子地址：[email protected]。
8
    国立成功大学附属医院内科，国立成功大学，台湾国立成功大学传染病与信号研究中心，台湾台南。电子地址：[email protected]。

抽象

慢性乙型肝炎（CHB）的进展与单核苷酸多态性（SNP）相关。在这项研究中，我们证明了具有免疫活性的CHB患者中与免疫相关的SNP与延迟的自发性HBeAg血清转化之间的关联。此外，我们调查了抗病毒治疗期间3年内延迟的自发性HBeAg血清转化相关SNP对HBeAg血清转化的影响。我们使用ABI OpenArray作为平台，招募了332名CHB患者并对与HBV感染的临床结果相关的124个SNP进行了基因分型，包括32个白介素相关基因，62个HLA基因，9个CD标记基因，7个NK细胞受体基因和14个其他基因。 。逻辑分析表明，将具有自发性HBeAg血清转化延迟（持续性HBeAg血清阳性，年龄大于40岁）的免疫活性CHB患者与早期无效的HBeAg血清转化（高病毒血症的HBeAg血清转化，小于40岁）的患者进行了逻辑分析，发现rs3820998（TANK） ，rs2621377（HLA-DOB），rs3130215（HLA-DPB2），rs2255336（KLRK1）和rs11614913（MIR-196A2）与延迟的自发性HBeAg血清转化密切相关。使用多变量分析，我们确定高血清HBV DNA水平（OR = 1.66，95％CI = 1.33-2.08），rs3820998（CA，OR = 3.37，95％CI = 1.24-9.12），rs2621377（TC，OR = 4.96） ，95％CI == 1.85-13.3），rs2255336（TT，OR == 0.09、95％CI == 0.01-0.86）和rs11614913（TT，OR == 2.53、95％CI == 1.05-6.11）是以下5个独立的危险因素延迟自发性HBeAg血清转化。相反，在接受核苷酸（t）ide类似物治疗后，rs3820998杂合的CA变异体反而成为3年内治疗诱导的HBeAg血清转化的唯一独立的有利因素（OR = 0.21，95％CI = 0.06-0.78）。这些结果表明，在有或没有抗病毒治疗的情况下，具有免疫活性的CHB患者中，独特的免疫相关SNP在调节HBeAg状态中起着至关重要的作用。

版权所有©2020。由Elsevier B.V.发布。
关键字：

迟发性自发性HBeAg血清转换；早期无效的HBeAg血清转化；免疫活性慢性乙型肝炎；持久性HBeAg血清阳性；单核苷酸多态性

PMID：
    32004619
DOI：
    10.1016 / j.antiviral.2020.104719