拉米夫定抗乙型肝炎病毒感染中YMDD变异类型及时间研究  

Types and emergence time of YMDD motif mutation in hepatitis B virus polymerase gene during lamivndine treatmenttreatment

作　　者：梁伟峰[1] 沈月洪[1] 赵年丰[1] 杨丹红[2] 谢远军[3] 

机构地区：[1]浙江大学医学院附属第一医院感染科,杭州310003 [2]浙江大学医学院附属邵逸夫医院 [3]浙江中医学院针炙推拿系

出　　处：《中华肝脏病杂志》2003年第5期302-304,共3页Chinese Journal of Hepatology

基　　金：浙江省卫生厅科研基金(2000A096)

摘　　要：目的 研究拉米夫定抗乙型肝炎病毒(HBV)感染中P基因发生YMDD变异的类型和出现时间。方法 取拉米夫定治疗过程中HBV DNA由阴性再次转为阳性33例患者及HBV DNA始终保持阳性达一年或一年以上2例患者的血清,经PCR扩增HBV的P基因,对扩增产物进行测序及用3个限制性内切酶分析HBVP基因的YMDD变异。 结果 14例出现YMDD变异,其中6例YVDD变异,4例YIDD变异,3例YI/VDD混合变异,1例YI/MDD变异。变异出现时间平均为(11.07±3.65)个月,最短5个月,最长7个月。其中YIDD为(10.00±1.41)个月,YVDD为(11.67±4.41)个月,YI/VDD为(13.33±3.31)个月,三种变异类型的出现时间差异无显著性(F=0.543,P>0.05)。3例YMDD变异后拉米夫定加量至200mg/d,未能消除变异病毒。 结论 拉米夫定抗HBV感染后变异有多种形式,包括YIDD、YVDD、YI/VDD、YI/MDD。变异发生时间一般在治疗后(11.07±3.65)个月。变异类型与用药时间无关。Objective To study the types and emergence time of YMDD motif mutation in hepatitis B virus (HBV) polymerase gene during lamivudine treatment. Methods The serum samples were collected from 33 patients with HBV DNA rebounding and 2 non-responders after at least one year lamivudine treatment. HBV polymerase gene was amplificated by PCR, then the products were detected by restriction fragment length polymorphism (RFLP) and by direct sequence analysis. Results The variants with YMDD mutation were 14 out of the 35 patients. Mutation patterns detected in these patients included four YIDD, six YVDD, three YI/VDD and one YI/MDD. The mean emergence time of YMDD variants was 1 1.07 ± 3.65 months after the treatment, and the earliest one and the latest one occurred 5 months and 17 months after the treatment respectively. The emergence times of YIDD, YVDD, YI/VDD were (10.00 ± 1.41) months, (11.67 ± 4.41) months and (13.33 ± 3.31) months respectively, which had no statistical significance (F = 0.543, P < 0.05). Three patients treated with lamivudine 200 mg every day after the mutation were followed up for 6 months, whose HBV variants had not vanished. Conclusions There are many kinds of HBV variants after lamivudine treatment, including YIDD , YVDD, YI/VDD and YI/MDD. The emergence time of variants is quite variable between different types and the mean time is (11.07 ± 3.65) months after treatment, and there is no relationship between the type of YMDD mutation and the time of lamivudine administration.

关 键 词：拉米夫定 乙型肝炎病毒感染 YMDD 变异类型 时间 研究 

分 类 号：R512.62[医药卫生—内科学]