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目的探讨慢性乙型肝炎(慢乙肝)患者经核苷(酸)类药物抗病毒治疗的耐药突变连锁模式。方法采用平行等位基因特异性序列检测技术(parallel allele-specific sequencing,PASS)对106例经核苷(酸)类药物抗病毒治疗的慢乙肝患者进行13个耐药位点的检测,并分析其耐药突变连锁模式。结果 90例检测到发生耐药突变,其中76.7%(69例)发生耐药位点连锁突变,连锁模式达39种。最主要的2个连锁突变模式为M204V+L180M和M204V+L180M+V173L,所占比例分别为58.0%(40例)和46.4%(32例),其次是M204I+L80I和M204V+V173L,所占比例分别为17.4%(12例)和15.9%(11例)。结论经核苷(酸)类药物抗病毒治疗的慢乙肝患者中广泛存在多个耐药位点的连锁突变,以拉米夫定相关耐药位点的连锁模式最常见。
Objective To investigate the drug-resistant mutation chain model of nucleoside (acid) drugs in patients with chronic hepatitis B (chronic hepatitis B). Methods Totally 13 drug-resistant loci were detected in 106 patients with chronic hepatitis B treated with nucleoside (antiviral) drugs by parallel allele-specific sequencing (PASS) Its drug-resistant mutation chain mode. Results 90 cases of drug-resistant mutations were detected, of which 76.7% (69 cases) of the drug-resistant loci were found to be linked mutation and the linkage pattern reached 39 kinds. The two main linkage mutations were M204V + L180M and M204V + L180M + V173L, accounting for 58.0% (40 cases) and 46.4% (32 cases), followed by M204I + L80I and M204V + V173L, respectively The proportions were 17.4% (12 cases) and 15.9% (11 cases), respectively. Conclusions There are many linkage mutations of multiple drug resistance sites in patients with chronic hepatitis B treated with nucleoside (antiviral) antiviral therapy. The linkage mode with lamivudine related resistance sites is the most common.