分析低水平 HBsAg 的慢性无症状 HBV 携带者的临床特征和 S 基因序列。

Analysis of clinical characteristics and S gene sequences in chronic asymptomatic HBV carriers with low-level HBsAg.

机构信息

Faculty of Graduate Studies, Bengbu Medical College, Bengbu 233000, PR China; Department of Clinical Research, The 117th Hospital of PLA, Hangzhou 310013, PR China; Faculty of Graduate Studies, Jiangsu University, Zhenjiang 212013, PR China.

Department of Laboratory Medicine, Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, PR China; Faculty of Graduate Studies, Jiangsu University, Zhenjiang 212013, PR China.

出版信息

Clin Res Hepatol Gastroenterol. 2019 Apr;43(2):179-189. doi: 10.1016/j.clinre.2018.08.015. Epub 2018 Oct 4.

DOI:10.1016/j.clinre.2018.08.015

PMID:30293895

Abstract

BACKGROUND

During the natural hepatitis B virus (HBV) infection process, some infected subjects are characterized by a sustained low serum HBV surface antigen (HBsAg) expression level. Most members in this population are chronic asymptomatic HBV carriers (ASCs). To elucidate the mechanism underlying low-level HBsAg expression in ASCs, we sequenced the HBV S gene in these patients to reveal specific sequence characteristics.

METHODS

Overall, 1308 cases of chronic ASCs were grouped according to their HBsAg serum expression levels (10 IU/mL). The clinical characteristics of the population were analysed in detail. The HBV S gene was sequenced from 276 ASC cases with low-level HBsAg expression. Additionally, 100 of 1032 ASC cases with high-level HBsAg expression were randomly selected for HBV S gene sequencing based on age matching according to the low-level HBsAg group. A comparative analysis was conducted with the HBV S gene sequences from ASCs with low HBsAg expression and the HBV reference S gene sequences from ASCs with high HBsAg expression.

RESULTS

The population with low-level HBsAg expression displayed the following primary clinical characteristics: mostly chronic asymptomatic HBV carriers, older age (mean age 55.09 years), HBsAg/anti-HBe/anti-HBc (core) positivity as the main serological pattern (97.1%), low HBV DNA replication (1.32 ± 1.60 log IU/mL), a low HBV-DNA positive rate (45.65%) and primarily genotype B (82.54%) and serotype adw (84.13%). The comparative analysis of the HBV S gene sequences from ASCs with low-level HBsAg showed significant mutations (including co-mutations) on both sides of the main hydrophilic region (MHR).

CONCLUSION

Significant mutations in multiple regions and at multiple sites (including co-mutations) on both sides of the MHR may be one cause of the low HBsAg expression level in this population.

摘要

背景

在自然发生的乙型肝炎病毒（HBV）感染过程中，一些受感染的个体表现为持续低水平的血清 HBV 表面抗原（HBsAg）表达。该人群中的大多数成员为慢性无症状 HBV 携带者（ASCs）。为了阐明 ASCs 中低水平 HBsAg 表达的机制，我们对这些患者的 HBV S 基因进行了测序，以揭示特定的序列特征。

方法

根据 HBsAg 血清表达水平（10IU/ml），将 1308 例慢性 ASC 患者分为两组。详细分析了人群的临床特征。对 276 例低 HBsAg 表达的 ASC 病例的 HBV S 基因进行了测序。此外，根据低 HBsAg 组，根据年龄匹配随机选择了 1032 例高 HBsAg 表达的 ASC 病例中的 100 例进行 HBV S 基因测序。对低 HBsAg 表达的 ASC 的 HBV S 基因序列与高 HBsAg 表达的 ASC 的 HBV 参考 S 基因序列进行了比较分析。

结果

低 HBsAg 表达人群的主要临床特征为：主要为慢性无症状 HBV 携带者，年龄较大（平均年龄 55.09 岁），HBsAg/抗-HBe/抗-HBc（核心）阳性为主要血清学模式（97.1%），HBV DNA 复制水平较低（1.32±1.60logIU/ml），HBV-DNA 阳性率较低（45.65%），主要基因型为 B（82.54%）和血清型 adw（84.13%）。对低 HBsAg 表达的 ASC 的 HBV S 基因序列进行比较分析显示，主要亲水区域（MHR）两侧的多个区域和多个位点（包括共突变）存在显著突变。