论文部分内容阅读
目的分析大样本慢性乙型肝炎患者HBV反转录酶基因上的多位点核苷(酸)类似物的耐药相关突变情况及其临床意义。方法提取1 121例患者血清HBV DNA,采用巢式PCR方法扩增HBV反转录酶(RT)基因,对PCR产物进行DNA双向测序,对12个位点上的耐药相关突变进行检测,并结合临床资料进行分析。结果检出拉米夫定(LAM)耐药突变228例,阿德福韦(ADV)耐药突变32例,恩替卡韦(ETV)耐药突变13例,替比夫定(L-dT)耐药突变4例。多药耐药5例。LAM耐药突变中以M204V和M204I最常见,前者通常伴随L180 M突变,后者常单独出现;ADV耐药突变中以N236T±A181位碱基替换为主;ETV耐药突变发生在LAM耐药基础上,以T184位碱基替换为主;L-dT的耐药突变为M204I。结论用基因序列测定法检测HBV RT基因多位点耐药相关突变,有助于临床及时发现乙肝患者是否存在HBV基因耐药,合理进行抗病毒治疗。
OBJECTIVE: To analyze the resistance-related mutations in multi-site nucleoside (acid) analogues of HBV reverse transcriptase gene in patients with chronic hepatitis B and their clinical significance. Methods Serum HBV DNA was extracted from 121 cases of patients. HBV reverse transcriptase (RT) gene was amplified by nested PCR. The products of PCR were bi-directionally sequenced and the resistance-related mutations in 12 sites were detected. Combined with clinical data analysis. Results 228 cases of LAM resistance mutation, 32 cases of adefovir dipivoxil resistance mutation, 13 cases of ETV resistance mutation and L-dT drug resistance were detected. Mutation in 4 cases. Multidrug resistance in 5 cases. LAM resistance mutations in the most common M204V and M204I, the former usually accompanied by L180 M mutation, the latter often appear alone; ADV resistance mutations to N236T ± A181 base replacement; ETV resistance mutations in LAM resistance Based on the T184 base replacement; L-dT resistance mutation M204I. Conclusion Detection of HBV RT gene multi-site drug-resistance-related mutations using gene sequence analysis is helpful to discover whether there is HBV drug resistance in HBV patients in a timely manner and to conduct antiviral therapy reasonably.