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越南慢性 HBV 感染治疗失败患者乙型肝炎病毒逆转录酶序列中的耐药突变。

Resistant mutations within the hepatitis B virus reverse transcriptase sequence in treatment failure patients with chronic HBV infection in Vietnam.

机构信息

Department of Viology and Parasitology, National Hospital for Tropical Diseases, Hanoi, Vietnam; Department of Infectious Diseases, Hanoi Medical University, Hanoi, Vietnam.

Department of Microbiology and Molecular Diagnostic, National Hospital for Tropical Diseases, Hanoi, Vietnam.

出版信息

J Glob Antimicrob Resist. 2023 Jun;33:35-41. doi: 10.1016/j.jgar.2023.02.013. Epub 2023 Feb 26.

Abstract

OBJECTIVES

We conducted this study to describe whether mutations in the gene coding for the enzyme reverse transcriptase (RT) were related to drugs used in the treatment of hepatitis B in Vietnam.

METHODS

Patients receiving antiretroviral therapy with evidence of treatment failure were included in the study. The RT fragment was cloned using the polymerase chain reaction technique after being extracted from patients' blood samples. The nucleotide sequences were analysed using Sanger method. The HBV drug resistance database contains mutations associated to resistance to existing HBV therapies. Medical records were accessed to collect information on patient parameters, such as treatment, viral load, biochemistry, and blood count.

RESULTS

Resistance mutations to lamivudine, telbivudine, and entecavir were found in the highest proportion (75-91.7%) of HBV samples from patients who had failed antiretroviral therapy. Only 20.8% of HBV strains had mutations exhibiting adefovir resistance, while none had mutations conferring tenofovir resistance. M204I/V, L180M, and L80I are frequent variants linked with resistance to lamivudine, telbivudine, and entecavir. In contrast, the A181L/T/V mutation was detected predominantly in tenofovir-resistant HBV strains. Following the drug resistance mutation test, patients achieved the greatest virological response after 24 weeks of therapy with tenofovir and entecavir at a daily dose of one tablet.

CONCLUSION

Lamivudine, telbivudine, and entecavir were all highly resistant to the RT enzyme modifications in 24 treatment failure patients, with M204I/V, L180M, and L80I being the most prevalent mutations. Tenofovir resistance mutations have not been found in Vietnam.

摘要

目的

本研究旨在描述乙型肝炎病毒(HBV)逆转录酶(RT)编码基因的突变是否与越南抗乙型肝炎病毒治疗药物的使用相关。

方法

本研究纳入了接受抗逆转录病毒治疗但治疗失败的患者。从患者的血液样本中提取 RT 片段后,使用聚合酶链反应技术进行克隆。使用 Sanger 法对核苷酸序列进行分析。HBV 耐药数据库包含与现有 HBV 治疗耐药相关的突变。查阅病历,收集患者参数信息,如治疗、病毒载量、生化和血常规。

结果

在抗逆转录病毒治疗失败的患者的 HBV 样本中,发现了对拉米夫定、替比夫定和恩替卡韦耐药的突变,占比最高(75-91.7%)。仅有 20.8%的 HBV 株具有阿德福韦耐药突变,而无一株具有替诺福韦耐药突变。M204I/V、L180M 和 L80I 是与拉米夫定、替比夫定和恩替卡韦耐药相关的常见变异体。相比之下,A181L/T/V 突变主要存在于对替诺福韦耐药的 HBV 株中。耐药突变检测后,24 例治疗失败的患者接受替诺福韦和恩替卡韦(每日一片)治疗 24 周后,获得了最大的病毒学应答。

结论

在 24 例治疗失败的患者中,拉米夫定、替比夫定和恩替卡韦均对 RT 酶修饰高度耐药,M204I/V、L180M 和 L80I 是最常见的突变。在越南尚未发现替诺福韦耐药突变。

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