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Prevalence of Hepatitis B Antiviral Drug Resistance Variants in North American Patients with Chronic Hepatitis B Not Receiving Antiviral Treatment

机译:北美未接受抗病毒治疗的慢性乙型肝炎患者中乙型肝炎抗病毒药物耐药性的发生率

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摘要

Antiviral 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.
机译:抗病毒药物抗性HBV变异体(HBV-DR)在慢性乙型肝炎(CHB)患者中自发出现,并暴露于核苷酸(t)ide类似物(NUCs)之后。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)队列研究参与者中HBV-DR变异的患病率。从S342≥18岁的CHB参与者(目前未接受NUC)获得的样本通过Sanger测序进行了HBV-DR变异检测。此外,使用下一代测序(NGS)来表征来自66位参与者的HBV-DR变异体,以及66位参与者先前没有NUC暴露与HBV基因型和HBV DNA水平相匹配的参与者。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%)参与者中检测到了主要的HBV-DR变体:2/142名(1.4%)患儿和14/1200名(1.2%)无NUC暴露;这16个中只有1个具有次要变体。总共有23名(1.7%)参与者患有继发性变体,其中1名具有NUC先前的经历。在132名参与者的子集中,NGS在更高比例的参与者中检测到HBV-DR变体:18例(13.6%)的原发性变种[8(12.1%),未接受NUC治疗的有10例(15.2%)],以及继发性10位参与者(7.6%)的变体形式。根据Sanger测序,在美国/加拿大,患有CHB的成年人中原发性HBV-DR变异的患病率较低(1.2%)。在接受和不接受NUC治疗的受试者中,HBV-DR变异的患病率相似,这表明这些变异的传播并不常见。

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