慢性乙型肝炎替比夫定相关耐药突变15例回顾性分析  

Telbivudine-resistant mutation in patients with chronic hepatitis B:a retrospective study of 15 cases

作　　者：杨芳[1] 王磊 

机构地区：[1]山东大学医学院,济南250012 [2]第二医院感染肝病科,济南250033

出　　处：《山东大学学报（医学版）》2011年第4期129-132,共4页Journal of Shandong University:Health Sciences

摘　　要：目的研究慢性乙型肝炎(CHB)患者替比夫定(LdT)相关耐药的HBV聚合酶基因突变模式及临床特点。方法对LdT治疗中病毒学突破的HBeAg阳性CHB,经焦磷酸测序法证实为LdT耐药突变的15例患者进行回顾性分析。结果共检出4个耐药突变位点呈5种模式,分别为rtM204I 9例,rtM204I+rtL180M 3例,rtM204I+rtV173L、rtM204I+rtV173L+rtL180M和rtM204I+rtV173L+rtA181V各1例。治疗24周时患者血清HBV-DNA均<104拷贝/mL,其中60%(9/15)的患者<103拷贝/mL;耐药突变发生于用药后40～111周,均未出现HBeAg血清学转换。结论 rtM204I是LdT耐药的主要突变模式,对未出现HBeAg血清学转换的患者,即使在24周HBV-DNA<103拷贝/mL,仍需关注其耐药突变。Objective To study mutation patterns of telbivudine（LdT）-resistant in the HBV P gene and clinical features in patients with chronic hepatitis B（CHB）.Methods 15 patients with hepatitis B e antigen（HBeAg）-positive CHB that had a virological breakthrough and LdT-resistent mutation confirmed by the pyro-sequencing method were retrospectively analyzed.Results 5 mutation patterns at 4 sites of LdT-resistant were detected,rtM204I in 9 cases,rtM204I＋rtL180M in 3 cases,and rtM204I＋rtV173L,rtM204I＋rtV173L＋rtL180M and rtM204I＋rtV173L＋rtA181V in each 1 case.Serum HBV-DNA levels of all the 15 patients were below 104 copies/mL after 24 weeks of LdT treatment,60%（9/15） of which were below 103copies/mL.Resistant mutations were detected from 40 to 111 weeks and all patients failed to take on HBeAg sero-conversion.Conclusions RtM204I is the main mutation pattern of LdT-resistance.Resistant mutation should still be of concern for patients who fail to take on HBeAg sero-conversion even if serum HBV-DNA is below 103 copies/mL at week 24.

关 键 词：肝炎 乙型 慢性 突变 替比夫定 焦磷酸测序 

分 类 号：R512.62[医药卫生—内科学]