替比夫定抗病毒治疗不同时间慢性乙型肝炎患者HBV P基因RT区序列突变模式及耐药率的改变

目的：通过研究替比夫定治疗不同时间慢性乙型肝炎患者HBV P基因RT区序列突变模式及耐药率的改变，探讨替比夫定的主要耐药变异模式及耐药率。方法：应用重组克隆测序检测法检测47例接受替比夫定治疗1、2、5年的慢性乙型肝炎患者HBV P基因区序列。结果：应用替比夫定治疗1年者有2例（4.26%）出现常见变异位点，P基因区突变模式均为rtM204I；治疗2年者有10例（21.28%）出现变异位点，9例突变模式为rtM204I，1例突变模式为rtL180M+rtM204I；治疗5年者有24例（51.06%）检测到替比夫定常见变异位点，16例（66.7%）变异模式为rtM204I、4例（16.7%）为rtL180M+rtM204I,另外还有rtL181V+rtM204I、rtM204V、rtM204I+rtN238H、rtL180M +rtM204I+rtD263E各1例。结论:替比夫定的主要耐药变异模式为rtM204I和rtL180M+rtM204I。替比夫定治疗1、2、5年的耐药率分别为4.26%、21.28%和51.06%。提示替比夫定的5年耐药率明显低于拉米夫定的4年耐药率，但替比夫定的耐药率高于阿德福韦酯。

Changes of HBV P gene RT region mutation model and drug-resistant rate in patients with chronic hepatitis B treated with telbivudime for different time

Objective Through the study on HBV P gene sequences of RT resistance mutation patterns and drug resistence of telbivudine in treating with the chronic HBV infeceted patients to discuss the main resistance mutation patterns and drug resistence of telbivudine.Methods The recombinant clone sequencing assay was used to detect HBV P gene sequence in 47 patients who received telbivudine treatment for 1 year,2 years,and 5 years.Results In the patients received telbivudine treatment for one year,2 cases(4.26%)had common variable sites,P gene region of mutation patterns was rtM204I;for 2 years,10 cases(21.28%)had variable sites,9 cases of mutation model rtM204I,1 case mutation model rtL180M + rtM204I;for 5 years,24 cases(51.06%)had common variable sites variation patterns,16 cases(66.7%)of rtM204I,4 cases(16.7%)of rtL180M + rtM204I.There were also rtL181V + rtM204I,rtM204V,rtM204I + rtN238H,rtL180M + rtM204I + rtD263E each 1 case.Conclusion The main telbivudine resistance mutation models are rtM204I and rtL180M + rtM204I.The resistance rates of telbivudine treatment for 1,2,5 years are 4.26%,21.28%,and 51.06%,respectively.And the 5-year resistance rate is significantly lower than that of the 4-year resistance rate of lamivudine,but the resistance rate of telbivudine is higher than that of adefovir.