Front Immunol:中国南方河源市隐匿性乙型肝炎病毒感染献血者中发现的高频显著HBV突变

2022-07-01 从医路漫漫 MedSci原创

OBI被定义为在窗口期(WP)之外,血浆和/或肝脏中存在非常低水平的HBV DNA,伴有检测不到的乙型肝炎表面抗原(HBsAg),有或没有乙型肝炎核心抗原抗体(抗-HBc)或乙型肝炎表面抗体

背景及目的:尽管在过去十年中,由于实施了更合适的筛查方法,如HBsAg ELISA结合核酸检测(NAT ),输血传播的HBV感染显著减少,但隐匿性乙型肝炎病毒感染(OBI)仍然是血液安全的主要威胁。OBI被定义为在窗口期(WP)之外,血浆和/或肝脏中存在非常低水平的HBV DNA,伴有检测不到的乙型肝炎表面抗原(HBsAg),有或没有乙型肝炎核心抗原抗体(抗-HBc)或乙型肝炎表面抗体(抗-HBs)。OBI可以通过输血传播,在某些情况下,当宿主免疫功能下降或受到抑制时,它也可以发展为HBV感染。这可能导致慢性肝损伤以及乙肝相关肝硬化和肝细胞癌的发展。先前的研究表明,即使使用ID NAT,中国志愿献血者中OBI的患病率也远高于邻近的亚洲国家和西方国家,特别是自2015年以来MP NAT已在中国全国范围内实施。中国献血者中OBIs的高患病率可能对血液安全构成潜在威胁。河源是中国广东省东北部的一个中等城市,约有300万居民。自2016年1月1日起,河源市血液中心在对所有献血者进行HBsAg、抗-HCV和抗-HIV两轮ELISA筛查的同时,对HBV DNA、HCV RNA和HIV RNA进行了MP8格式的核酸检测。在常规筛查过程中,发现了一些HBsAg-/HBV DNA+的献血者。为了确保血液安全,尤其是在HBV高流行国家,如中国,需要进一步澄清这些献血者在OBIs流行率、DNA突变和临床结果方面的不一致结果。

在目前的研究中,我们对从HBsAg-/HBV DNA+ (OBI)献血者中扩增的HBV DNA片段进行了HBV DNA突变分析。确定了可能影响HBsAg检测的各种显著突变。这些突变可能影响HBsAg检测,导致可能潜在地危及血液安全的OBIs。此外,我们进行了为期3年的随访研究,以进一步分析这些OBIs的临床结果。我们后续研究的结果表明,大多数OBIs仍然是病毒载量波动或较低的OBIs。因此,更高灵敏度的HBV ID NAT推荐用于献血者筛查,以进一步降低来自具有OBIs的献血者的传播风险。

方法:用HBsAg ELISA和HBV MP8 NAT对河源市献血者进行筛查。本研究收集了带有HBsAg-/HBV DNA+的捐献物。通过各种DNA扩增试验,包括定量PCR (qPCR)和巢式PCR,扩增基本核心和前核心启动子区(BCP/PC),进一步分析HBV DNA的分子特征。通过高容量核酸提取从HBV DNA中分离出HBsAg (S)区。通过与HBV参考序列比较,鉴定出显著的突变。对OBIs供体的临床结果进行了近3年的随访。

结果:来自44,592名捐献者(0.15%)的70名obi参与了本次研究。从44/70 OBIs中获得HBV序列,基因型分析显示42/44 (95.2%) OBIs为基因型B,2/ 44 (4.8%)为基因型c。有趣的是,突变分析显示在基因型B OBIs中观察到影响HBsAg检测的HBV DNA的各种突变,包括M133L/T、F134L、P142L、V168A、R169H、S174N、L175S和V177A。在基因型C的OBIs中发现了两个显著的突变,T47K和L53S。随访研究表明,3/31 (9.7%)的OBIs转变为HBsAg+慢性感染,而1/ 31 (3.2%)的HBV DNA检测不到(归类为恢复),27/31 (87.1%)仍为OBIs。

表1在患有OBIs的当地献血者中,MHR和B基因型MHR外的显著突变。

表2  31名OBI和1名WP捐献者的随访分析。

结论:河源地区有OBIs的献血者中存在多种影响HBsAg检测的显著突变。随访研究表明,大多数OBIs仍然是病毒载量波动或较低的OBIs。为进一步降低OBIs的传播风险,建议对献血者进行更高灵敏度的HBV ID NAT筛查。

原文出处: Ye X,  Liu L,  Chen L, et al.High-Frequency Notable HBV Mutations Identified in Blood Donors With Occult Hepatitis B Infection From Heyuan City of Southern China.Front Immunol 2022;13

 

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    2022-08-15 klivis
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    2022-07-01 ms5000000518166734

    学习学习学习学习学习学习学习学习学习学习学习学习学习学习学习学习学习学习学习学习学习学习学习学习学习

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