乙型肝炎病毒核苷（酸）类似物耐药研究进展

doi:10.3877/cma.j.issn.1674-1358.2018.01.001

核苷（酸）类似物耐药问题是慢性乙型肝炎抗病毒治疗中的重要问题之一。随着核苷（酸）类似物耐药研究的不断进展，耐药检测新技术逐渐被研发，对病毒变异的机制了解更加精确且全面。核苷（酸）类似物新的可疑耐药位点不断被提出，但这些位点的临床意义尚待进一步明确。尤其是慢性乙型肝炎患者应用核苷（酸）类似物抗病毒治疗的过程即是病毒与机体相互作用的过程逐渐被认知，在此过程中病毒准种及全基因组序列存在动态演变。核苷（酸）类似物耐药仅为此相互作用过程的表现之一，应将核苷（酸）类似物耐药放在机体免疫与病毒相互作用的整体背景下进行研究。

关键词: 肝炎、乙型、慢性, 肝炎病毒、乙型, 耐药

Nucleos(t)ide analogues resistance is still one of the most important questions in management of patients with chronic hepatitis B. New techniques to detecting resistant mutations were developed, showing the resistance more precisely and comprehensively. New possible variants related to nucleos(t)ide analogues resistance were identified, but the clinical significance still need to be verified. The researches on nucleos(t)ide analogues resistance as one of the manifestations in dynamic interaction between HBV and host immunity during nucleos(t)ide analogues therapy were realized. And nucleos(t)ide analogues resistance in the background of virus-host interaction should be understanded.

Key words: Chronic hepatitis B, Hepatitis B virus, Resistance

表1 已获得广泛认可的NAs耐药位点与部分尚处于研究阶段的NAs耐药位点

NAs种类	耐药变异	对该变异的认识现状
LAM	rtM204V/I ± rtL180M	广泛认可的耐药变异^[1,23]
	rtA181T	广泛认可的耐药变异^[1,23]
	L80I	待确认的补偿变异^[24]
	rtS117F	待确认的补偿变异^[25]
	rtL229	待确认的补偿变异^[26]
	rtM204Q	待确认的耐药变异^[27]
	rtQ267H	待确认的补偿变异^[29]
	rtL269	待确认的补偿变异^[30]
ADV	rtA181T/V	广泛认可的耐药变异^[1,23]
	rtN236T	广泛认可的耐药变异^[1,23]
	rtA181S	待确认的耐药变异^[28]
	rtQ215H	有争议的耐药变异^[31,32]
	rtI233V	有争议的耐药变异^{[33,34,35,36,37]}
LdT	rtM204V/I ± rtL180M	广泛认可的耐药变异^[1,23]
	rtA181T	广泛认可的耐药变异^[1,23]
ETV	rtM204V/I ± rtL180M基础上 + rtI169、rtT184、rtS202或rtM250任一个或多个位点变异	广泛认可的耐药变异^[1,23]
	rtI163V	待确认的耐药变异^[38]
	rtA186T	待确认的耐药变异^[38]
TDF	rtA194T	待确认的耐药变异^[39]
	rtP177G	待确认的耐药变异^[40]
	rtF249A	待确认的耐药变异^[40]
	rtA181T + rtN236T	待确认的耐药变异^[41]

表1 已获得广泛认可的NAs耐药位点与部分尚处于研究阶段的NAs耐药位点

NAs种类	耐药变异	对该变异的认识现状
LAM	rtM204V/I ± rtL180M	广泛认可的耐药变异^[1,23]
	rtA181T	广泛认可的耐药变异^[1,23]
	L80I	待确认的补偿变异^[24]
	rtS117F	待确认的补偿变异^[25]
	rtL229	待确认的补偿变异^[26]
	rtM204Q	待确认的耐药变异^[27]
	rtQ267H	待确认的补偿变异^[29]
	rtL269	待确认的补偿变异^[30]
ADV	rtA181T/V	广泛认可的耐药变异^[1,23]
	rtN236T	广泛认可的耐药变异^[1,23]
	rtA181S	待确认的耐药变异^[28]
	rtQ215H	有争议的耐药变异^[31,32]
	rtI233V	有争议的耐药变异^{[33,34,35,36,37]}
LdT	rtM204V/I ± rtL180M	广泛认可的耐药变异^[1,23]
	rtA181T	广泛认可的耐药变异^[1,23]
ETV	rtM204V/I ± rtL180M基础上 + rtI169、rtT184、rtS202或rtM250任一个或多个位点变异	广泛认可的耐药变异^[1,23]
	rtI163V	待确认的耐药变异^[38]
	rtA186T	待确认的耐药变异^[38]
TDF	rtA194T	待确认的耐药变异^[39]
	rtP177G	待确认的耐药变异^[40]
	rtF249A	待确认的耐药变异^[40]
	rtA181T + rtN236T	待确认的耐药变异^[41]

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Progress in hepatitis B virus resistance to nucleos(t)ide analogues

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Progress in hepatitis B virus resistance to nucleos(t)ide analogues