在慢性感染的HBsAg和抗HBs合并感染的患者中，乙型肝炎病毒“

StephenW

Clin Res Hepatol Gastroenterol. 2019 Oct 14. pii: S2210-7401(19)30189-5. doi: 10.1016/j.clinre.2019.08.005. [Epub ahead of print]
Characteristics of amino acid substitutions within the "a" determinant region of hepatitis B virus in chronically infected patients with coexisting HBsAg and anti-HBs.
Hou W1, Huo Z2, Du Y3, Wang C4, Syn WK5.
Author information

1
    Tianjin Second People's Hospital and Tianjin Institute of Hepatology, Tianjin, China; Division of Gastroenterology and Hepatology, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA. Electronic address: [email protected].
2
    Tianjin Second People's Hospital and Tianjin Institute of Hepatology, Tianjin, China.
3
    Department of Biomedical Engineering, School of Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Tsinghua University, Beijing, China.
4
    Division of Gastroenterology and Hepatology, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA.
5
    Division of Gastroenterology and Hepatology, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA; Section of Gastroenterology, Ralph H Johnson Veterans Affairs Medical Center, Charleston, SC, USA; Department of Physiology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Spain. Electronic address: [email protected].

Abstract
OBJECTIVES:

Simultaneous positivity for both hepatitis B surface antigen (HBsAg) and antibodies to HBsAg (anti-HBs) is an atypical serological profile in chronic hepatitis B (CHB) patients. The exact mechanisms underlying the uncommon profile remains unclear. The aim of this study was to analyze the characteristics of amino acid substitutions within the "a" determinant region in a large cohort of CHB patients with coexistence of HBsAg and anti-HBs.
METHODS:

In total 8687 CHB patients, of which 505 had coexisting HBsAg and anti-HBs, were enrolled in this study. Mutations within the "a" determinant region in 131 HBsAg+/anti-HBs+ patients and 150 age and gender matched HBsAg+/anti-HBs- patients were determined by direct sequencing and the characteristics of amino acid substitutions were analyzed.
RESULTS:

The prevalence of coexistence of HBsAg and anti-HBs in the CHB patients was 5.81%. Compared to the control subjects, there were more amino acid substitutions in HBsAg+/anti-HBs+ patients (30.5% vs. 12.7%, P<0.001), especially within the first loop of the "a" determinant region. The most frequent amino acid substitution was located at position s126 and the predominant substitution was sI126T in HBsAg+/anti-HBs+ patients with genotype C. The frequency of additional N-glycosylation sites in HBsAg+/anti-HBs+ patients and the control subjects was 3.8% and 0.6%, respectively.
CONCLUSIONS:

The accumulation and diversity of amino acid variations within "a" determinant region might contribute to the coexistence of HBsAg and anti-HBs. These findings extend understanding of the genetic mechanism of this atypical serological profile in CHB patients.

Copyright © 2019 Elsevier Masson SAS. All rights reserved.
KEYWORDS:

Amino acid substitution; Anti-HBs; Chronic hepatitis B; HBsAg; “a” determinant region

PMID:
    31624004
DOI:
    10.1016/j.clinre.2019.08.005

StephenW

Clin Res Hepatol胃肠酸。 2019年10月14日.pii：S2210-7401（19）30189-5。 doi：10.1016 / j.clinre.2019.08.005。 [Epub提前发布]
在慢性感染的HBsAg和抗HBs合并感染的患者中，乙型肝炎病毒“ a”决定簇区域内的氨基酸取代特征。
侯W1，霍Z2，杜Y3，王C4，Syn WK5。
作者信息

1个
天津市第二人民医院和天津市肝病研究所，天津；美国南卡罗来纳州医科大学，胃肠病学和肝病学系，医学系。电子地址：[email protected]。
2
天津市第二人民医院和天津市肝病研究所，天津。
3
清华大学医学院生物医学工程系，传染病诊治协同创新中心，北京。
4
美国南卡罗来纳州医科大学，胃肠病学和肝病学系，医学系。
5
美国南卡罗来纳州医科大学医学院胃肠病学和肝病学系；美国南卡罗来纳州查尔斯顿，拉尔夫·H·约翰逊退伍军人事务医疗中心消化内科；西班牙巴斯克大学（UPV / EHU），医学和护理学院生理学系。电子地址：[email protected]。

抽象
目标：

慢性乙型肝炎（CHB）患者的乙型肝炎表面抗原（HBsAg）和抗HBsAg抗体（抗HBs）同时呈阳性。罕见的概况背后的确切机制仍不清楚。这项研究的目的是分析大量HBsAg和抗HBs共存的CHB患者队列中“ a”决定簇区域内的氨基酸取代特征。
方法：

本研究共纳入8687名CHB患者，其中505名同时存在HBsAg和抗HBs。通过直接测序确定131名HBsAg + /抗-HBs +患者和150名年龄和性别匹配的HBsAg + /抗-HBs患者“ a”决定簇内的突变，并分析氨基酸取代的特征。
结果：

CHB患者中HBsAg和抗HBs并存的患病率为5.81％。与对照组相比，HBsAg + /抗-HBs +患者的氨基酸取代更多（30.5％vs. 12.7％，P <0.001），尤其是在“ a”决定簇区域的第一个环内。在基因型C的HBsAg + /抗HBs +患者中，最频繁的氨基酸替换位于s126位置，主要替换为sI126T。HBsAg+ /抗HBs +患者和对照组的其他N-糖基化位点频率为3.8％和0.6％分别。
结论：

“ a”决定簇区域内氨基酸变异的积累和多样性可能有助于HBsAg和抗HBs的共存。这些发现扩展了对CHB患者这种非典型血清学特征的遗传机制的了解。

版权所有©2019 Elsevier Masson SAS。版权所有。
关键字：

氨基酸取代；抗HBs；慢性乙型肝炎；乙肝表面抗原“ a”行列式区域

PMID：
31624004
DOI：
10.1016 / j.clinre.2019.08.005