拉米夫定耐药患者乙型肝炎病毒多聚酶区变异分析及恩替卡韦治疗观察  

The mutation analysis of the reverse transcriptase domain and enticavir for treatment in lamivudine-resistant chronic hepatitis B patients

作　　者：高得勇[1] 刘亮明[1] 王迎迎[1] 徐国荣[1] 汪妍妍 俞小燕[1] 

机构地区：[1]上海交通大学附属第一人民医院松江分院感染科,上海201600

出　　处：《泰山医学院学报》2011年第3期169-172,共4页Journal of Taishan Medical College

摘　　要：目的观察拉米夫定耐药的慢性乙型肝炎患者多聚酶区耐药基因突变的分布,以及恩替卡韦治疗拉米夫定失效患者的疗效。方法采用PCR产物直接测序法对45例出现拉米夫定变异的慢性乙肝患者血清进行检测(HBV)P区基因RT区序列耐药变异;应用恩替卡韦1 mg/d进行治疗,分别在治疗前、治疗后12周、24周、36周、48周检测肝功能(ALT)、HBV-DNA水平、HBV血清标志物的变化;以初始应用恩替卡韦0.5 mg/d治疗的慢性乙型肝炎患者作为对照研究。结果 45例拉米夫定耐药患者中32例(71%)出现YMDD变异,19例(42%)发生rtL180M+rtM204V联合变异;LAM耐药患者经恩替卡韦治疗48周后有88.9%出现血清ALT复常和血清HBV DNA转阴,与对照组相比无显著差异(P>0.05);其中30例HBeAg阳性的LAM耐药患者中有3例发生HBeAg/抗-HBe血清转换率,明显低于对照组(P<0.05);治疗过程中HBV DNA均值的变化也明显低于对照组(P<0.05)。结论拉米夫定耐药患者HBV P区基因变异呈现多样性,恩替卡韦1 mg/d治疗拉米夫定耐药的慢性乙型肝炎患者有效。Objective： To explore the characteristics of mutaition in HBV polymerase（P） gene reverse transcriptase region（RT region） and characterize the therapeutic efficacy of entecavir in lamivudine-resistant chronic hepatitis B（CHB） patients.Methods： This study involved 45 CHB patients who had received lamivudine treatment and developed clinical resistance to lamivudine.Direct sequencing of HBV reverse transcriptase region which was amplified by PCR was used to detect lamivudine genotypic resistance.Patients of CHB who had received lamivudine treatment and developed lamivudine resistance before switched to entecavir（1.0mg/d,monotherapy 48 weeks）.Virological and serologic response and laboratory data of liver function of each patient enrolled were monitored every 12 weeks.As the control,a total of 30 chronic HBV infected patients in our hospital were treated with entecavir 0.5mg per day.Results： The major and the combined mutations including YMDD and rtL180M＋rtM204V were detected in 45 lamivudine resistant patients,accounting for 71% and 42% respectively.Of the 45 lamivudine refractory CHB patients,40 had normal ALT levels（40IU/L） and undetectability in HBV DNA level（103 copies/ml） after 48 weeks of entecavir therapy with a dose of 1.0mg/d.There was no statistical significance between lamivudine refractory CHB patients and the controls after the entecavir treatment.Three of thirty HBeAg positive patients（10%） achieved HBeAg serconversion in 48 weeks.The percentage of HBeAg serconversion was significantly lower than that of the controls（P0.05）.HBV DNA was decreased significantly more slowly than that of the controls during the process of entecavir treatment（P0.01）.Conclusion： The major mutation forms of lamivudine-resistant is rtM204V/I through the analysis of the multiple sites at HBV P gene RT region.Entecavir therapy with a dosage of 1.0mg/d is effective in treating lamivudine-resistant chronic hepatitis B（CHB） patients.

关 键 词：慢性乙型肝炎 拉米夫定耐药 变异 恩替卡韦 

分 类 号：R512.62[医药卫生—内科学]