替诺福韦酯挽救治疗HBV DNA聚合酶区204位点突变的经治慢性乙型肝炎患者疗效及安全性分析

目的探讨应用替诺福韦酯(TDF)挽救治疗HBV DNA聚合酶区204位点突变的经治的慢性乙型肝炎(CHB)患者的疗效及安全性。方法 2013年8月～2015年12月我院诊治的CHB患者87例,纳入患者均为曾接受拉米夫定(LAM)或阿德福韦酯(ADV)治疗6个月以上,血清HBV DNA阴转后又复阳,且经检测出现rtl204v耐药者,43例接受恩替卡韦(ETV)治疗,另44例接受TDF治疗,观察疗效,并使用流式细胞仪检测外周血CD4^+T淋巴细胞计数,常规计算内生肌酐清除率(Crcl)。结果在治疗24 w、48 w和72 w时,TDF治疗组血清HBV DNA阴转率分别为63.6%、79.6%和95.5%,显著高于ETV治疗组【分别为35.6%、55.6%和82.2%,P<0.05】,血清ALT复常率分别为84.1%、90.9%和93.2%,而ETV治疗组则分别为65.1%(P<0.05)、83.7%和90.7%;TDF治疗组外周血CD4+T细胞计数分别为(481.5±232.4)/μl、(536.5±297.5)/μl和(566.5±321.6)/μl,与ETV治疗组比,无显著性差异【分别为(475.3±229.3)/μl、(565.8±255.9)/μl和(565.1±256.5)/μl,P<0.05】;Crcl分别为(101.2±40.1)ml/min、(104.3±26.8) ml/min和(98.7±21.5) ml/min,与ETV治疗组比,无显著性差异【分别为(105.2±42.6)ml/min、(102.5±30.6) ml/min和(99.6±26.8) ml/min,P<0.05】。结论 TDF和ETV挽救治疗对核苷(酸)类治疗耐药的经治CHB患者均有良好的疗效,但似乎TDF起效更快,而ETV用量较大,不应列为首选。

Efficacy and safety of tenofovir disoproxil fumarate and entecavir in the treatment of chronic hepatitis B patients with viral DNA polymerase 204 site mutation infection

Objectiv To explore the efficacy and safety of tenofovir disoproxil fumarate（TDF） and entecavir （ETV） in the treatment of chronic hepatitis B （CHB） patients with viral DNA polymerase 204 site mutation infection. Methods 87 CHB patients with HBV polymerase 204 site mutation infection due to resistance to lamivudine or adefovir therapy were recruited in this study between August of 2013 and September 2015,and 44 patients received TDF and 43 received ETV treatment. The peripheral CD4⁺T lymphocyte counts were detected by FCM,and creatinine clearance （Crcl） was calculated based on serum creatinine levels. Results At the end of 24 w,48 w and 72 w treatment,serum HBV DNA loss in TDF-treated patients were 63.6%,79.6% and 95.5%,significantly higher than 35.6%,55.6% and 82.2%,respectively,in ETV-treated patients（P<0.05）,and serum ALT normalization rates were 84.1%,90.9% and 93.2%,while they were 65.1%（P<0.05）,83.7% and 90.7% in ETV-treated patients;the peripheral blood CD4⁺T cell counts were （481.5±232.4）/μl,（536.5±297.5）/μl and （566.5±321.6）/μl,no significantly different as compared to （475.3±229.3）/μl,（565.8±255.9）/μl and （565.1± 256.5）/μl in ETV-treated patients （P<0.05）;the Crcl levels were （101.2±40.1） ml/min,（104.3±26.8） ml/min and （98.7±21.5） ml/min,also without significantly different as compared to （105.2±42.6） ml/min,（102.5±30.6） ml/min and （99.6±26.8） ml/min in ETV-treated patients（P<0.05）. Conclusion TDF might be the priority option in dealing with CHB patients with HBV mutant infection for rescue therapy as it works early,convenient and safe.