摘要
目的明确临床实际工作中ADV治疗≥48周未获病毒学应答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≥48周未获病毒学应答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、HBV DNA载量等因素的相关性。结果共收集104例ADV治疗≥48周未获病毒学应答患者,共检出基因型耐药22例,耐药位点25个;耐药变异以rt A181T变异为主(60%)。既往LAM经治换用ADV患者ADV耐药检出率显著高于ADV初治患者(χ2=5.448,P=0.020);本组患者中能否检出ADV耐药变异与患者ADV治疗时间(t=1 212.5,P=0.647)、送检耐药时HBV DNA载量(t=1.648,P=0.102)以及应用ADV治疗病毒下降速度(t=1 135.5,P=0.877)无显著相关性。结论 ADV治疗≥48周未获病毒学应答患者ADV基因型耐药检出率为21.15%,其中以rt A181T位点变异为主;提示对于ADV长期治疗应答不理想的患者,即使未出现病毒学突破,也应酌情考虑进行耐药检测。
Objective To investigate the genotype resistance profile in real-life patients with chronic hepatitis B who got suboptimal response after≥48 weeks adefovir dipivoxil （ADV） treatment and clinical factors related to ADV resistance. Methods The clinical data and serum samples were collected from patients with CHB who got suboptimal response after≥48 weeks for ADV treatment. The genotype resistance of ADV was detected by PCR products direct-sequencing and pyrosequencing. Correlation between resistance and treatment history, HBV DNA level, etc were analyzed, respectively. Results Total of 104 patients with CHB were enrolled and ADV genotype resistance were found in 22/104 patents. There were 25 （60%） ADV resistance mutations were identiifed and rtA181T was the most common resistant mutation. Less resistance were identiifed in ADV na？ve patients than patients who took lamivudine/ADV sequential therapy （χ2=5.448, P=0.020）. ADV resistant positive was not signiifcantly related to ADV treatment duration （t=1 212.5, P=0.647）, HBV DNA level when detecting （t=1.648, P=0.102） and ratio of HBV DNA decline during treatment （t = 1 135.5, P = 0.877）. Conclusions About 21.15%ADV treated patients who got suboptimal response after≥48 weeks ADV treatment were identiifed as ADV genotype resistance. RtA181T was the most common resistant mutation. Patients got suboptimal response after long-term ADV treatment should consider drug resistance analysis even without virological breakthrough.
出处
《中华实验和临床感染病杂志（电子版）》
CAS
2015年第1期10-13,共4页
Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition)
基金
"十二五"国家科技重大专项项目(No.20122X10004904)
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)
关键词
阿德福韦酯
耐药
肝炎
乙型
慢性
焦磷酸测序
Adefovir dipivoxil
Resistance
Chronic hepatitis B
Pyrosequencing
