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肝胆相照论坛 论坛 学术讨论& HBV English 中国慢性乙型肝炎患者未接受核苷类似物的潜在耐药相关变 ...
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中国慢性乙型肝炎患者未接受核苷类似物的潜在耐药相关变 [复制链接]

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发表于 2020-8-10 17:46 |只看该作者 |倒序浏览 |打印
Prevalence of Potential Resistance Related Variants Among Chinese Chronic Hepatitis B Patients Not Receiving Nucleos(T)ide Analogues
Fuchu Qian  1   2 , Weihua Zou  3 , Fang Jin  1   2 , Dongli Li  1   2 , Yujuan Shen  4
Affiliations
Affiliations

    1
    Department of Precision Medicine, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, People's Republic of China.
    2
    Huzhou Key Laboratory of Molecular Medicine, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, People's Republic of China.
    3
    Department of Laboratory Medicine, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, People's Republic of China.
    4
    Department of Infectious Diseases, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, People's Republic of China.

    PMID: 32765014 PMCID: PMC7381783 DOI: 10.2147/IDR.S249476

Free PMC article
Abstract

Background and aims: Potential drug resistance (DR) related variants in the hepatitis B virus (HBV) reverse transcriptase (RT) region may be associated with the effectiveness of antiviral drugs and disease progression. The aim of this study was to investigate the prevalence and clinical characteristics of potential DR-related variants in Chinese CHB patients not receiving nucleos(t)ide analogues (NAs).

Patients and methods: Two hundred and six untreated CHB patients from Huzhou Central Hospital in eastern China were recruited for this study. The serum DNA was extracted and the HBV RT region was amplified using nest polymerase chain reaction (nest-PCR). The 42 potential DR-related variants were analyzed by direct sequencing.

Results: Among these CHB patients, HBV genotype B and genotype C were identified in 121 (58.7%) and 85 (41.3%) patients, respectively. Potential DR-related variants were detected in 42.7% (88/206) of patients. Primary and secondary DR variants were found in 7.3% (15/206) of patients, including rtL80I/V, rtI169T, rtV173L rtL180M, rtA181T/V, rtM204I/V, and rtN236T. The variants at rt53, rt82, rt221, rt233, rt237, and rt256 were specific for genotype B, and those at rt38, rt84, rt126, rt139, rt153, rt191, rt214, rt238, and rt242 were specific for genotype C. Moreover, the variation frequency in the A-B interdomain (3.96%) was significantly higher than that in the functional domains (1.17%) and non-A-B interdomains (1.11%). Multivariate logistic regression analysis showed that lower HBV-DNA load (<106 IU/mL) was an independent factor associated with potential DR-related variants in untreated CHB patients (P <0.05).

Conclusion: Potential DR-related variants were frequent and complex in untreated Chinese CHB patients. Furthermore, the variants may contribute to decreased serum HBV-DNA loads. However, the effects of potential DR-related variants on the antiviral therapy and liver disease progression require further study.

Keywords: Hepatitis B virus; potential; resistance; reverse transcriptase; variants.

© 2020 Qian et al.

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发表于 2020-8-10 17:46 |只看该作者
中国慢性乙型肝炎患者未接受核苷类似物的潜在耐药相关变异的患病率
府初1 2,邹伟华3,方进1 2,李东立1 2,沉玉娟4
隶属关系
隶属关系

    1个
    湖州大学附属湖州中央医院湖州市中心医院精密医学科,中华人民共和国湖州。
    2
    湖州大学附属中心医院湖州市中心医院湖州分子医学重点实验室,中华人民共和国湖州。
    3
    湖州大学附属湖州市中心医院湖州中心医院检验科,中华人民共和国湖州。
    4
    湖州大学附属湖州市中心医院湖州市中心医院感染科,中华人民共和国湖州。

    PMID:32765014 PMCID:PMC7381783 DOI:10.2147 / IDR.S249476

免费PMC文章
抽象

背景和目的:乙型肝炎病毒(HBV)逆转录酶(RT)区域中潜在的耐药性(DR)相关变异可能与抗病毒药物的有效性和疾病进展有关。这项研究的目的是调查未接受核苷酸类似物(NAs)的中国CHB患者中潜在的DR相关变异的患病率和临床特征。

患者和方法:招募了来自中国东部湖州市中心医院的206名未经治疗的CHB患者进行此项研究。提取血清DNA,并使用巢式聚合酶链反应(巢式PCR)扩增HBV RT区。通过直接测序分析了42种潜在的DR相关变体。

结果:在这些CHB患者中,分别有121(58.7%)和85(41.3%)患者被确定为HBV基因型B和C基因型。在42.7%(88/206)的患者中检测到了潜在的DR相关变异。在7.3%(15/206)的患者中发现了原发性和继发性DR变异,包括rtL80I / V,rtI169T,rtV173L rtL180M,rtA181T / V,rtM204I / V和rtN236T。 rt53,rt82,rt221,rt233,rt237和rt256的变异体是基因型B特有的,而rt38,rt84,rt126,rt139,rt153,rt191,rt214,rt238和rt242的变异体是C型。 AB域之间的变化频率(3.96%)显着高于功能域(1.17%)和非AB域之间的变化频率(1.11%)。多变量logistic回归分析显示,未治疗的CHB患者中较低的HBV-DNA负荷(<106 IU / mL)是与潜在的DR相关变异相关的独立因素(P <0.05)。

结论:未经治疗的中国CHB患者潜在的DR相关变异频繁且复杂。此外,这些变体可能有助于降低血清HBV-DNA负荷。但是,潜在的DR相关变体对抗病毒治疗和肝病进展的影响需要进一步研究。

关键词:乙型肝炎病毒;潜在;抵抗性;逆转录酶变体。

©2020 Qian等人。

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才高八斗

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发表于 2020-8-10 17:47 |只看该作者
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