北美慢性乙型肝炎患者未接受抗病毒治疗的乙型肝炎抗病毒

StephenW

J Viral Hepat. 2017 Jun 5. doi: 10.1111/jvh.12732. [Epub ahead of print]
Prevalence of Hepatitis B Antiviral Drug Resistance Variants in North American Patients with Chronic Hepatitis B Not Receiving Antiviral Treatment.Lok AS1, Ganova-Raeva L2, Cloonan Y3, Punkova L2, Lin HS3, Lee WM4, Ghany MG5; Hepatitis B Research Network (HBRN).
Author information
1University of Michigan, Ann Arbor, MI.2Centers for Disease Control and Prevention, Division of Viral Hepatitis Laboratory Branch, Atlanta, GA.3Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA.4University of Texas Southwestern Medical Center, Dallas, TX.5Liver Diseases Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD.

AbstractAntiviral drug resistance HBV variants (HBV-DR) occur spontaneously in chronic hepatitis B (CHB) patients and after exposure to nucleos(t)ide analogues (NUCs). We determined the prevalence of HBV-DR variants among participants of the Hepatitis B Research Network (HBRN) Cohort Study conducted at 21 sites in the United States (US) and Canada. Samples obtained from 1342 CHB participants aged ≥18 years, and who were currently not receiving NUCs, were tested for HBV-DR variants by Sanger sequencing. In addition, next generation sequencing (NGS) was used to characterize HBV-DR variants from 66 participants with and 66 participants with no prior NUC exposure matched for HBV genotype and HBV DNA level. Half the participants were men, 75% Asian, 26% HBeAg-positive. Primary HBV-DR variants were detected by Sanger sequencing in 16 (1.2%) participants: 2/142 (1.4%) with and 14/1200 (1.2%) without prior NUC exposure; only 1 of these 16 had a secondary variant. In total, 23 (1.7%) participants had secondary variants, including 1 with prior NUC experience. In the subset of 132 participants, NGS detected HBV-DR variants in a higher proportion of participants: primary variants in 18 (13.6%) [8 (12.1%) with, and 10 (15.2%) without prior NUC therapy], and secondary variants in 10 (7.6%) participants. Based on Sanger sequencing, prevalence of primary HBV-DR variants is low (1.2%) among adults with CHB in US/Canada. The similar low prevalence of HBV-DR variants in participants with and without NUC treatment suggests transmission of these variants is uncommon. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

KEYWORDS: Sanger sequencing; antiviral treatment; hepatitis B virus; next generation sequencing; nucleos(t)ide analogues

PMID:28581155DOI:10.1111/jvh.12732

StephenW

J病毒肝2017年6月5日。doi：10.1111 / jvh.12732。 [提前印刷]
北美慢性乙型肝炎患者未接受抗病毒治疗的乙型肝炎抗病毒药物耐药性变异流行率。
Lok AS1，Ganova-Raeva L2，Cloonan Y3，Punkova L2，Lin HS3，Lee WM4，Ghany MG5;乙肝研究网络（HBRN）。
作者信息

1
    密歇根大学，安娜堡，MI。
2
    疾病控制与预防中心，病毒性肝炎实验室分部，亚特兰大，GA。
3
    匹兹堡大学流行病学系，匹兹堡，宾夕法尼亚州。
4
    得克萨斯大学西南医学中心，达拉斯，德克萨斯州。
五
    国家糖尿病研究所，国家卫生研究院，消化和肾脏疾病分会，贝塞斯达，MD。

抽象

抗病毒药物耐药性HBV变异体（HBV-DR）在慢性乙型肝炎（CHB）患者和暴露于核心（t）ide类似物（NUCs）后自发发生。我们确定了在美国（美国）和加拿大的21个地点进行的乙型肝炎研究网络（HBRN）队列研究的参与者中HBV-DR变体的患病率。通过Sanger测序对来自1342位年龄≥18岁的CHB参与者和目前未接受NUCs的样品进行HBV-DR变体的检测。此外，下一代测序（NGS）用于表征来自66名参与者的HBV-DR变体，并且66名参与者没有先前的NUC暴露匹配HBV基因型和HBV DNA水平。一半的参与者是男性，75％为亚洲人，26％为HBeAg阳性。在16例（1.2％）参与者中，通过Sanger测序检测到原发性HBV-DR变体：2/142（1.4％）和14/1200（1.2％），未经NUC暴露;这16个中只有1个具有次要变体。共有23名（1.7％）参加者有次要变种，其中1名具有先前的NUC经验。在132个参与者的子集中，NGS检测到HBV-DR变体在较高比例的受试者中：18例（13.6％）[8（12.1％）]和10例（15.2％）未发生NUC治疗的原发性变异10名（7.6％）参与者的变体。基于Sanger测序，在美国/加拿大的CHB成年人中HBV-DR变体的HBV-DR变异率低（1.2％）。在具有和不具有NUC治疗的参与者中HBV-DR变体的相似低发生率表明这些变体的传播是不常见的。本文受版权保护。版权所有。

本文受版权保护。版权所有。
关键词：

桑格测序;抗病毒治疗;乙型肝炎病毒;下一代测序;核苷（t）ide类似物

结论：
    28581155
DOI：
    10.1111 / jvh.12732