江苏徐州地区核苷类似物疗效不佳的慢性乙型肝炎621例血清乙型肝炎病毒耐药突变分析

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.

Mutation analysis of HBV resistance in 621 patients with chronic hepatitis B after the treatment of nucleoside analogue in Xuzhou

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.