Prevalence of hepatitis B antiviral drug resistance variants in North American patients with chronic hepatitis B not receiving antiviral treatment
Prevalence of hepatitis B antiviral drug resistance variants in North American patients with chronic hepatitis B not receiving antiviral treatment
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DOI：
10.1111/jvh.12732
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发表时间：
2017-11-01
影响因子：
2.5
通讯作者：
Ghany, M. G.
中科院分区：
文献类型：
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作者：
Lok, A. S.;Ganova-Raeva, L.;Ghany, M. G.
慢性乙型病毒性肝炎(CHB)患者暴露于核糖核酸(T)类似物(NUCs)后，会自发产生抗病毒耐药的乙肝病毒(HBVDR)变异株。我们确定了在美国和加拿大21个地点进行的乙肝研究网络(HBRN)队列研究参与者中的乙肝病毒-DR变异体的流行率。从1342名年龄为18岁、目前没有接受免疫接种的慢性乙肝患者身上获得的样本，通过Sanger测序进行了乙肝病毒-DR变异的检测。此外，下一代测序(NGS)被用来表征66名参与者和66名既往没有暴露于NUC的参与者的HBVDR变异，这些参与者与HBV型和HBVDNA水平相匹配。一半的参与者是男性，75%的亚洲人，26%的HBeAg阳性。通过Sanger测序，在16名(1.2%)参与者中检测到主要的HBVDR变异：2/142(1.4%)有既往NUC暴露，14/1200(1.2%)未接触NUC；这16人中只有1人有次级变异。总体而言，23名参与者(1.7%)有继发性变异，包括1名既往有NUC经验的参与者。在132名参与者中，NGS在更高比例的参与者中检测到了乙肝病毒-DR变异：18名(13.6%)(8名[12.1%]接受过NUC治疗，10名[15.2%]未接受过NUC治疗)和10名(7.6%)参与者的次级变异。根据桑格测序，在美国和加拿大的慢性乙肝成人中，主要的乙肝病毒-DR变异体的流行率很低(1.2%)。接受NUC治疗和不接受NUC治疗的参与者中，乙肝病毒-DR变异的低流行率相似，这表明这些变异的传播并不常见。
Antiviral drug resistance hepatitis B virus (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.