慢性乙型肝炎患者阿德福韦酯治疗出现病毒学突破的耐药分析  

Genotype resistance profile in patients with chronic hepatitis B who underwent virological breakthrough during adefovir dipivoxil treatment

作　　者：杨松[1] 邢卉春[1] 王琦[2] 王笑梅[1] 欧蔚妮[1] 段英[1] 李贲[1] 李玥[1] 刘顺爱[2] 成军[1,2] 

机构地区：[1]首都医科大学附属北京地坛医院肝病中心,北京100015 [2]首都医科大学附属北京地坛医院传染病研究所,北京100015

出　　处：《中华实验和临床感染病杂志（电子版）》2014年第3期94-97,共4页Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition)

基　　金：中国肝炎防治基金会光辉基金资助项目(No.GHF20100207);北京市优秀人才培养资助D类项目(No.2012D003034000030);首都卫生发展科研专项项目(No.首发2011-2017-02)

摘　　要：目的明确临床实际工作中阿德福韦酯(ADV)治疗出现病毒学突破患者基因型耐药情况并对耐药相关因素进行分析。方法收集ADV治疗出现病毒学突破患者的血清样本及临床资料,应用PCR产物直接测序法联合焦磷酸测序法进行基因型耐药检测;分析基因型耐药与患者抗病毒治疗经过、基线HBV DNA载量等因素的相关性;并进一步分析rtA181T变异患者的病毒学及生化学指标变化。结果共收集106例ADV治疗出现病毒学突破患者,共检出基因型耐药45例,耐药位点67个;既往LAM等经治换用ADV患者ADV耐药检出率显著高于ADV初治患者(χ2=6.584,P=0.010);rtA181T耐药变异患者HBV DNA较最低值升高水平显著高于不包含rtA181T变异患者(t=566.000,P=0.014);包含rtA181T变异患者生化学突破率显著高于不包含rtA181T变异患者(χ2=5.140,P=0.023)。结论本组患者数据提示ADV治疗出现病毒学突破患者基因型耐药发生率约为40%,rtA181位点变异多于rtN236位点变异,rtA181T变异虽抑制耐药株病毒复制,但导致患者出现生化学突破几率并未减少。ObjectiveTo investigatethe genotype resistance proifle in patients with real-life chronic hepatitis B who underwent virological breakthrough during adefovirdipivoxil（ADV）treatment and clinical factors related toADV resistance.Methods Theclinical data and serum samples were collected from CHB patients who underwent virological breakthrough duringADV treatment. PCR products direct-sequencing and pyrosequencing were used for detectingADV genotype resistance. Correlation between resistance and treatment history, baseline HBV DNA level etc were analyzed, respectively. Virological and biochemical features of rtA181T resistance were analyzed.Results Total of106 CHB patients were enrolled andADV genotype resistance were found in 45patents while 67ADV resistance mutations were identified. Less resistance were identiifed inADVna？ve patients than that in patients who took lamivudine/ADV sequential therapy （χ2= 6.584,P = 0.010）.ADV resistant patients carrying rtA181T mutation had lower level HBV DNA rise from nadir than patients without rtA181T mutation （t= 566.000,P=0.014）.More patients with rtA181T mutation underwent biochemical breakthrough than patients without rtA181T mutation （χ2= 5.140, P = 0.023）.ConclusionsAbout 40%ADV treated patients who underwent virological breakthrough were identiifed asADV genotype resistance. RtA181 resistance mutation was more common than rtN236 forADV resistance. RtA181T mutation may inhibit HBV replication and cause no less biochemical breakthrough than otherADV resistance mutations.

关 键 词：阿德福韦酯 耐药 肝炎 乙型 慢性 焦磷酸测序 ADEFOVIR dipivoxil (ADV) 

分 类 号：R512.62[医药卫生—内科学]