HBV基因型与耐药变异的关系

Relationship between HBV genotypes and drug-resistance mutations

目的探讨乙型肝炎病毒（HBV）基因型与核苷（酸）类似物耐药变异的关系。方法湖南省衡阳地区122例慢性乙型肝炎患者接受拉米夫定治疗（100mg／d）48-96周，发生耐药变异者改用阿德福韦酯治疗（10mg／d）96周。采用直接测序法进行HBV基因分型，同时检测拉米夫定、阿德福韦酯和恩替卡韦耐药变异位点。结果122例慢性乙型肝炎患者中，B基因型86例（70．49%），C基因型24例（19．67％），未分型12例（9．84％）。42例检出拉米夫定变异株，其中B基因型32例，C基因型10例，B、C基因型拉米夫定耐药变异率分别为37．21％（32／86）和41．67％（10／24），差异无显著性（x^2=0．16，P=0．69）；42例经阿德福韦酯治疗48周和96周的变异发生率分别为0．00％（0／42）和2．38％（1／42），B、C基因型阿德福韦酯耐药变异率分别为3．13％（1／32）和0．00％（0／10）。拉米夫定耐药变异类型主要为rtM204V＋rtL180M（35．71％）和rtM204I（38．10％）；B、C基因型比较，拉米夫定耐药变异类型差异无显著性（x^2=17．44，P=0．23）。结论湖南省衡阳地区HBV基因型以B型为主，C型次之；HBV基因型对拉米夫定耐药变异发生率及变异类型无明显影响。

Objective To study the relationship between HBV genotypes and nucieolide analogues drug-resistance mutations. Methods One hundred and twenty-two patients with chronic hepatitis B were treated with lamivudine 100mg/d for 48-96 weeks, patients who developed lamivudine-resistance mutations used adefovir dipivoxil 10mg/d for 96 weeks instead of lamivudine. HBV genotypes, lamivudine, adefovir dipivoxil and entecavir resistance mutations were determined by DNA sequencing. Results Among 122 cases, 86 （70. 490/6o） were genotype B, 24 （19. 67%） were genotype C, and 12（9. 84%） were not classified. 42 lamivudine-resistance mutants （32 mutants of genotype B, and 10 mutants of genotype C） were found in 122 cases. The incidence of mutations was 37. 21%（32/ 86） and 41.67 % （10/24） in HBV genotypes B and C, respectively, there was no significant difference between the two （X^2 = 0. 16,P = 0. 69）. The incidence of mutations was 0. 00%（0/42） and 2. 38%（1/42） in 42 patients treated with adefovir dipivoxil for 48 and 96 weeks, respectively, the incidence of adefovir dipivoxil mutations was 3. 13% （1/32） and 0. 00%（0/10） in genotypes B and C, respectively. The main types of lamivudine-resistance mutations were rtM204V ＋ rtL180M（35.71%） and rtM204I（38.10 % ） ; Lamivudine-resistance mutation types showed no significant difference between HBV genotypes B and C（x^2（2 = 17. 44, P = 0. 23）. Conclusion HBV genotype B is the most prevalent, and genotype C is the second in Hengyang of Hunan. HBV genotypes have no obvious influence on the incidences and types of mutation during lamivudine therapy.