拉米夫定联合阿德福韦酯治疗前后乙型肝炎病毒的全基因组序列分析

目的探究拉米夫定治疗反弹后联合阿德福韦酯治疗前后乙型肝炎全基因组序列变化。方法分别提取服用拉米夫定治疗24周反弹后和阿德福韦酯辅助治疗24周后的患者2份血清病毒核酸，用聚合酶链反应扩增核酸后进行全基因组测序分析。结果测序结果显示，共计有29个氨基酸发生了突变，其中，S区突变点有5个（17．2％），C区突变点有12个（41．3％），P区突变点有6个（20．6％），X区突变点有6个（20．6％），其中P区与拉米夫定的相关位点173和204位点发生了突变翻转，但服用阿德福韦后出现了与之相关的突变位点（181、214、236和237位点）。结论核苷酸药物的使用和HBV基因耐药突变密切相关，定期检测HBV基因突变对于合理使用核苷酸药物具有重要意义。

The whole genome sequence of HBV before and after Lamivudine combined with adefovir dipivoxil therapy in chronic hepatitis B patients

Objective To observe the variation of Hepatitis B Virus(HBV) genome before and after treatment of adefovir dipivoxil for rebounded load of HBV after treatment of Lamivudine.Method HBV DNA was extracted from the sera of chronic hepatitis B patients,with one serum sample taken from patients who received Lamivudine for 24 weeks,and the other sample taken from the same patients who then received adefovir dipivoxil for 24 weeks.The whole genome of HBV DNA was sequenced after amplification by polymerase chain reaction.Result By comparing the two whole genome sequences of HBV DNA,we found 29 mutations of amino acids,including 5 in S gene(17.2%),12 in C gene(41.3%),6 in P gene(20.6%),and 6 in X gene(20.6%).In P gene,two amino acids sites’(173 and 204) mutations were related to Lamivudine,but the other four sites’(181,214,236 and 237) mutations were related to adefovir dipivoxil.Conclusion Use of nucleotide analogues is related to drug resistance-associated mutation in HBV genomes.Detection for DNA mutation of HBV genome at regular intervals is significant for reasonable use of nucleotide analogues.