乙肝耐药全基因测序分析研究  

Whole gene sequencing of drug resistance on nucleoside(acid)analog anti-HBV

作　　者：姜静 万浩 李徐图 谢文英 蒋丽琳 杨瑞生 张平 孟冬梅 JIANG Jing;WAN Hao;LI Xutu;XIE Wenying;JIANG Lilin;YANG Ruisheng;ZHANG Ping;MENG Dongmei(Infection Marketing Department,Wuhan Kindstar Diagnostics Co.,Ltd.,Wuhan,Hubei 430000,China)

机构地区：[1]武汉康圣达医学检验所有限公司营销感染市场部,湖北省武汉市430000

出　　处：《中国医学工程》2020年第11期25-28,共4页China Medical Engineering

摘　　要：目的探讨接受核苷(酸)类药物抗病毒治疗的慢性乙型肝炎患者的耐药突变连锁模式。方法采用nest-PCR及测序方法对经抗病毒药物治疗的慢乙肝患者进行全基因测序,分析了126例样本的测序结果。结果126例样本的检测结果,发现发生耐药突变的74例。经过分析,其中发生耐药位点连锁突变的为49例(66.2%),连锁模式达36种。M204I位点突变13例;M204V位点单点突变或连锁突变共34例,M204V连锁M180L再联合其他位点突变的达30例,其中M180L+M204V+S202G为12例,占40%(12/30)。其中也发现可能对恩替卡韦耐药的L180M+M204V+A181G/C的突变。结论抗病毒治疗的慢性乙型肝炎患者中广泛存在多个耐药位点,随着临床用药,其他新的耐药突变模式也陆续出现。提示在接受核苷(酸)类药物抗病毒治疗前,在治疗过程中的合适时间点检测耐药相关变异位点,可为临床慢性乙型肝炎的抗病毒治疗提供重要参考。【Objective】To investigate the mutant linkage pattern of chronic hepatitis B patients receiving nucleoside(acid)antiviral therapy.【Methods】The whole gene was sequenced by nest-PCR and sequencing.The results of 126 samples were analyzed.【Results】The results of 126 samples showed that 74 of them had drug-resistant mutations.Through analysis,49 cases(66.2%)of them had linkage mutations of drug resistance sites,with 36 linkage patterns.A total of 34 M204 V single point mutations or linkage mutations,including 13 M204 I mutations,and up to 30 M180 L+M204 V linkage mutations combined with other mutations.M180 L+M204 V+S202 G were 12 cases,accounting for 40%(12/30).Mutations in L180 M+M204 V+A181 G/C that might be resistant to entecavir were also found.【Conclusion】There are many new drug resistance sites in patients with chronic hepatitis B treated with antiviral therapy.It is suggested that the detection of drug-resistant mutation sites before antiviral treatment with nucleoside(acid)drugs and at the appropriate time point during the treatment process can provide important reference for antiviral treatment of chronic hepatitis B.

关 键 词：乙型肝炎病毒 核苷(酸)类似物 耐药连锁突变 

分 类 号：R512.62[医药卫生—内科学]