YMDD变异阴性拉米夫定耐药的慢性乙型肝炎病毒感染临床研究  

Clinical study on negative mutation of YMDD in Lamivudine-resistant patients with chronic hepatitis B virus infection

作　　者：刘俊[1] 王丹华[2] 喻成波[3] 张秋芬[1] 叶玲玲[1] 

机构地区：[1]浙江省磐安县人民医院内二科,浙江磐安县322399 [2]浙江省磐安县人民医院内一科,浙江磐安县322399 [3]浙江大学医学院附属第一医院感染科,浙江杭州310003

出　　处：《中华医院感染学杂志》2015年第20期4685-4687,共3页Chinese Journal of Nosocomiology

基　　金：浙江省科技厅计划基金资助项目(201426)

摘　　要：目的探讨慢性乙型肝炎病毒（HBV）感染患者发生YMDD变异阴性拉米夫定耐药的机制,总结有效治疗方法,为提高其生存概率积累经验。方法选取医院2011年1月-2014年9月107例拉米夫定耐药的慢性HBV感染患者为研究对象,回顾性分析不同因素与拉米夫定耐药的慢性HBV感染患者YMDD变异阴性关系,将24例YMDD变异阴性拉米夫定耐药的慢性HBV感染患者采用随机数字法分为对照组12例及观察组12例,比较两组患者治疗前后肝功能各项指标及HBV-DNA水平。结果年龄≤25岁、服药时间≤2年、体质量指数〉25kg/m2、无合并症等可能是拉米夫定耐药的慢性HBV患者YMDD变异阴性主要原因;两组患者继续治疗前各项肝功能指标及HBV-DNA水平比较差异均无统计学意义,继续治疗24周后,观察组ALT、AST、GGT、ALP、HBV-DNA的血清水平显著低于对照组,差异有统计学意义（P〈0.05）;24例YMDD变异阴性患者均成功测序,有效序列长度为819bp（nt193-1012）,核苷酸变异率在0.79%～1.68%,氨基酸变异率在0.62%～2.04%,未发现rtL80V/I、rtL82M、rtF166L、rtV173L和rtA200V变异。结论 YMDD变异阴性慢性乙型肝炎病毒感染患者发生耐药的原因与HBV RT区基因变异无关,临床上应加强YMDD变异阴性患者的耐药检测,同时耐药的出现并非停止治疗的指标。OBJECTIVE To study the negative mutation of YMDD in Lamivudine‐resistant patients with chronic hepatitis B virus infection so as to conclude effective therapy and gather experience for improving survival rate . METHODS Totally 107 Lamivudine‐resistant patients with chronic hepatitis B virus infection were selected from Jan .2011 to Sep .2014 as study objects .Relation between different factors and negative mutation of YMDD in Lamivudine‐resistant patients with chronic hepatitis B virus infection were retrospectively analyzed .Among them , 24 Lamivudine‐resistant and YMDD negative patients with chronic hepatitis B virus infection were randomly divid‐ed into control group with 12 cases and observation group with 12 cases .All the indexes of liver function and HBV DNA level were compared between the two groups of patients before and after treatments .RESULTS Research found that age less than 25 years old ,medicine taking time less than 2 years ,BMI over 25 kg/m2 ,and complica‐tions were possible reasons of negative YMSS in Lamivudine‐resistant patients with chronic hepatitis B virus infec‐tion .Liver function and HBV‐DNA levels were similar in the two groups before treatments .After 24 weeks of treatments ,levels of ALT ,AST ,GGT ,ALP ,and HBV‐SNA in observation group were significantly lower than those of the control group （P〈0 .05） .All 24 negative mutation of YMDD patients were successfully sequenced , and the effective length of the sequence was 819bp （nt193‐1012） ,nucleotide mutation rate was between 0 .79% -1 .68% ,amino acid mutation rate was between 0 .62% -2 .04% .No mutation of rtL80V/I ,rtL82M ,rtF166L , rtV173L and rtA200V was found .CONCLUSION The negative mutation of YMDD in Lamivudine‐resistant patients with chronic hepatitis B virus infection was irrelevant to genovariation in RT section of HBV .Drug resistance should be examined in Lamivudine‐resistant and YMDD negative patients with chronic hepatitis B virus infection . And meanwhile ,treatments should not simply

关 键 词：YMDD变异阴性 拉米夫定 慢性乙型肝炎 发生机制 治疗 

分 类 号：R978.1[医药卫生—药品]