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作 者:蒋孝华[1] 李小芬[1] 蔡亚平[2] 李红梅[1]
机构地区:[1]南华大学附属第一医院,湖南衡阳421001 [2]南华大学流行病学教研室,湖南衡阳421001
出 处:《中国感染控制杂志》2009年第3期160-163,共4页Chinese Journal of Infection Control
基 金:湖南省自然科学联合基金项目(07JJ6165)
摘 要: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.
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