拉米夫定耐药乙型肝炎患者HBV多聚酶区基因突变的检测

Identification of gene mutations at HBV polymerase region in patients with lamivudine-resistant hepatitis B

目的:探讨拉米夫定(LAM)耐药乙型肝炎患者的乙肝病毒(HBV)多聚酶区基因突变特点。方法:收集94例接受LAM治疗且耐药的慢性乙型肝炎患者和50例非耐药的患者的血清,采用PCR产物直接测序法检测HBV多聚酶区序列耐药变异。结果:94例诊断为耐药的患者中,80例患者检测到LAM相关的HBV多聚酶区基因突变,其中单位点rtM204I突变占30.0%(24/80),rtLl80M+rtM204V为25.0%(20/80),rtLl80M+rtM204I为22.5%(18/80),rtVl73L+rtV180M+rtM204V为8.8%(7/80),而50例非耐药的患者中只有2例HBV多聚酶区基因突变。结论:LAM耐药相关的HBV聚合酶基因突变类型复杂多样,需要对多个相关位点进行检测,以便尽早发现耐药毒株,调整治疗方案。

Objective： To investigate the gene mutation patterns at hepatitis B virus（HBV） polymerase region in patients with lamivudine-resistant hepatitis B. Methods： The serum samples from 94 hepatitis B patients who underwent lamivudine treatment and developed resistance and another 50 hepatitis B patients without lamivudine resistance were collected.The resistant mutations at HBV polymerase gene region were detected by direct sequencing of PCR products. Results： Of the 94 lamivudine-resistant patients,80 cases were found with lamivudine-resistant mutations at HBV polymerase gene region,among which the single mutation at RtM204I was 30.4%（24/80）,and the alliance mutation of rtLl80M＋rtM204V was 25.0%（20/80）,rtLl80M ＋ rtM204I was 22.5%（18/80） and rtVl73L ＋ rtV180M ＋ rtM204V was 8.3%（7/80）,respectively.Only 2 cases of the 50 non-resistant patients had the HBV polymerase gene mutations. Conclusion： The lamivudine resistance-related mutations at HBV polymerase gene region are diverse and complex.Thus,multi-loci detection should be performed so as to find the drug resistance strains early and then adjust treatment plan accordingly.