核苷（酸）类药物治疗慢性乙型肝炎的耐药突变分析

摘要/Abstract

摘要： 目的分析核苷（酸）类药物治疗慢性乙肝诱导HBV基因耐药的变异特征。方法通过常规PCR和DNA反向斑点杂交相结合的DNA芯片技术对211例服用核苷（酸）类药物治疗慢性乙肝的耐药患者和195例未治疗的慢性乙肝患者进行HBV DNA基因分型和耐药位点检测,分析核苷（酸）类药物耐药突变规律。结果 406例患者中B基因型占61％,C基因型占31％,C基因型耐药突变发生率（65%）显著高于B基因型（46%）,差异有统计学意义（P<0.001）。rtM204I为最常见的耐药突变位点（43%）,rtM204V、rtL180M、rtM250V、rtA181T/V、rtN236T、rtM250L常与其它耐药位点相伴出现,rtT184S/A/I/L、rtS202G、rtM/V207I仅以多耐药模式存在。C基因型更容易发生公共耐药通路突变,耐药通路突变与患者的HBeAg状态无相关性。结论深圳地区HBV基因型以B型为主,C基因型较B基因型有更高的耐药突变发生率,且更容易发生公共耐药通路突变。

关键词: HBV, 耐药, 突变, 基因型

Abstract: Objective To clarify the characteristics of HBV resistance mutant induced by treatment of chronic hepatitis B with nucleos(t)ide analogues (NAs).Methods HBV DNA genotyping and drug resistance mutant detection were performed in 211 patients with chronic hepatitis B (CHB) treated with NAs and 195 NA-naïve patients with CHB via DNA chip technology which combines routine PCR and DNA reverse spot hybridization, and the characteristics of NAs resistance mutation was analyzed.Result sAmong the 406 samples, 61% were genotype B, 31% were genotype C, and the mutation rate of genotype C(65%) was significantly higher than that of genotype B(46%) (P<0.001). rtM204I was the most common resistance mutation site (43%). rtM204V, rtL180M, rtM250V, rtA181T/V, rtN236T and rtM250L were often accompanied by other resistance sites. RtT184S/A/I/L, rtS202G, rtM/V207I existed only in the multi-site resistance pattern.The genotype C was more prone to mutation in the shared pathway, and the mutation of the resistance pathways had no correlation with the patients’ HBeAg status.Conclusion The HBV genotypes in Shenzhen are mainly genotype B. Genotype C has a higher incidence of resistance mutation than genotype B, and is more likely to mutate in the shared pathway.

Key words: HBV, Drug resistance, Mutation, Genotype

陈洪涛, 何桂蓉, 杨智, 麦润章, 吴诗品. 核苷（酸）类药物治疗慢性乙型肝炎的耐药突变分析[J]. 新发传染病电子杂志, 2019, 4(1): 24-27.

CHEN Hong-tao, HE Gui-rong, YANG Zhi, MAI Run-zhang, WU Shi-pin. Investigation into drug-resistant mutations in the treatment of chronic hepatitis B with nucleos(t)ide analogues[J]. Electronic Journal of Emerging Infectious Diseases, 2019, 4(1): 24-27.

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核苷（酸）类药物治疗慢性乙型肝炎的耐药突变分析

Investigation into drug-resistant mutations in the treatment of chronic hepatitis B with nucleos(t)ide analogues

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