摘要
目的 探讨江苏徐州地区经核苷类似物治疗疗效不佳的慢性乙型肝炎患者HBV耐药基因突变分布特征.方法 收集2010年8月～2013年5月在我院就诊的门诊及住院慢性乙型肝炎患者血清标本621份,均为经核苷类似物治疗3个月以上且血清HBV DNA阳性者,采用核酸扩增技术结合荧光标记探针杂交方法对乙型肝炎病毒DNA进行定量检测,其产物通过测序分析进行耐药突变的检测,率的比较采用x2检验.结果 621例患者HBV耐药总变异检出率为75.8％（471/621）,其中拉米夫定、阿德福韦酯、替比夫定和恩替卡韦分别为88.9％ （144/162）、53.7％（108/201）、89.0％（47/53）和88.0％ （22/25）,服用过2种或者2种以上抗病毒药物者为83.3％（150/180）,以上5组间变异率总检出率比较差异有统计学意义（P＜0.05）,其中阿德福韦酯组与其他各组分别比较差异均有统计学意义（P＜0.05）,其他各组两两比较差异均无统计学意义（P＜0.05）.耐药变异病例数构成比服用过2种或者2种以上抗病毒药物者（31.8％）最高,拉米夫定、阿德福韦酯、替比夫定和恩替卡韦分别为30.6％、22.9％、10.0％和4.7％,以上5组构成比比较总差异有统计学意义（P＜0.05）.除拉米夫定组与服用过2种或者2种以上抗病毒药物组之间差异无统计学意义（P＞0.05）,其他各组两两比较差异均有统计学意义（P＜0.05）.比较各位点变异率,所检测的25个位点的总差异有统计学意义（P＜0.05）,204位点耐药突变率最高（243例次,39.1％）,其次是180位点（184例次,29.6％）、181位点（123例次,19.8％）,这3个位点两两比较或者分别与其他各位点比较差异均有统计学意义（P＜0.05）.结论 204位点、180位点、181位点耐药突变检出率高,恩替卡韦及替比夫定经治患者较少进行HBV耐药突变检测.
Objective To explore the distributional characteristics of HBV resistance mutation in chronic hepatitis B patients treated with nucleoside analogue in Xuzhou. Methods Six hundred and twen- ty-one chronic hepatitis B patients with positive HBV DNA received nucleoside analogue treatment, and their clinical data were analysed. Results Resistance mutations were found in 471 of 621 patients, the mutation rate was 75.8%. The mutation rate of lamivudine was 88.9% （ 144/162 ） , adefovir Dipivoxil was 53.7% （ 108/201 ）, telbivudine was 89.0% （47/53）, entecavir was 88.0% （ 22/25 ）, and the mutation rate of those who had received two or more nucleoside analogues was 83.3% （150/180） （P 〈 0.05）. The constituent ratios of resistance mutation cases in two or more nucleoside analogues, amivudine, telbivudine and entecavir were 31.8% ,30.6% , 10.0% and 4.7% respectively（ P 〈 0.05 ）. Mutation rate was the highest at codon 204（243,39.1% ）,followed at codon 180（ 184,29.6% ） and codon 181 （123,19.8%） （P 〈 O. 05）. Conclusion Mutations were higher at codon 204, codon 180, and codon 181 than other codons. Less detection of resistance mutation is proceeded in patients treated with entecavir and telbivudine.
出处
《临床内科杂志》
CAS
2014年第2期88-91,共4页
Journal of Clinical Internal Medicine
关键词
乙型肝炎
核苷类似物
耐药
突变
Hepatitis B
Nucleoside analogue
Drug resistance
Mutation
