在加上阿德福韦联合恩替卡韦治疗抢救延迟减少阿德福韦耐

StephenW

Int J Med Sci           2015; 12(5):416-422.  doi:10.7150/ijms.11687

Research Paper

Delayed Reduction of Hepatitis B Viral Load and Dynamics of Adefovir-Resistant Variants during Adefovir plus Entecavir Combination Rescue Therapy      

Yang Wang1, Shuang Liu1, Yu Chen1, Sujun Zheng1, Li Zhou1, Fengmin Lu2, Zhongping Duan1

         

1. Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China.
2. Department of Microbiology & Infectious Disease Center, Peking University Health Science Center, Beijing, China.

How to cite this article:
Wang Y, Liu S, Chen Y, Zheng S, Zhou L, Lu F, Duan Z. Delayed Reduction of Hepatitis B Viral Load and Dynamics of Adefovir-Resistant Variants during Adefovir plus Entecavir Combination Rescue Therapy. Int J Med Sci 2015; 12(5):416-422. doi:10.7150/ijms.11687. Available from  http://www.medsci.org/v12p0416.htm
AbstractObjective: Entecavir (ETV) added to adefovir (ADV) is recommended in the consensus for management of patients with ADV resistance. However, little attention has been focused on the delayed reduction of HBV DNA and dynamics of ADV-resistant variants during ADV-ETV combination rescue therapy in the clinical setting. We characterized the dynamics of viral load and resistant variants in nucleos(t)ide analogues (NAs)-naïve chronic hepatitis B (CHB) patients during antiviral treatment with ADV monotherapy followed by ADV-ETV combination therapy.
Methods: A cohort of 55 CHB patients was enrolled in this study. Three NAs-naïve patients developed ADV-resistant variants during 24-33 months of ADV monotherapy, and then switched to ADV-ETV combination therapy. Thirty-five serial serum samples from these three patients were regularly collected during treatment. Ten mutants associated with commonly used antiviral drugs were detected by pyrosequencing.
Results: HBV DNA decreased to the lowest level during ADV monotherapy at 6-18 months, with a decrease of 0.95-5.51 log10 copies/mL, whereas rtA181V or rtN236T gradually increased with extended therapy. HBV DNA decreased to below the detectable level during ADV-ETV combination therapy at 21-24 months, with a decrease of 4.19-4.65 log10 copies/mL. Resistant rtA181V and rtN236T were undetectable after 21-24 months of combination therapy. Moreover, no LAM-resistant rtM204I/V or ETV-resistant variants were detected during the 27-36 months of combination therapy.
Conclusion: Although ADV-resistant variants were suppressed, viral load reduction was delayed during ADV-ETV combination rescue therapy in patients with ADV-resistant HBV. The quantification of resistant variants by pyrosequencing may facilitate monitoring of antiviral therapy.
Keywords: adefovir, entecavir, hepatitis B virus, rescue therapy, resistance

StephenW

诠释J医学科学2015年; 12（5）：416-422。 DOI：10.7150 / ijms.11687

研究论文
在加上阿德福韦联合恩替卡韦治疗抢救延迟减少阿德福韦耐药变异的乙肝病毒载量和动力学

杨旺1，爽Liu1，玉臣1，苏俊Zheng1，李Zhou1，丰民LU2，中平Duan1通讯地址

1.人工肝中心，北京佑安医院，首都医科大学，北京100069，中国。
微生物学和传染病中心，北京大学医学部，北京，中国2部。
如何引用这​​篇文章：
王勇，刘S，陈Y，郑S，周升，吕男，段Z.阿德福韦，恩替卡韦加结合抢救治疗过程中减少延迟的阿德福韦耐药变异乙肝病毒载量和动力学。诠释J医学科学2015年; 12（5）：416-422。 DOI：10.7150 / ijms.11687。可从http://www.medsci.org/v12p0416.htm
抽象

目的：恩替卡韦（ETV）加入到阿德福韦（ADV）被推荐为患者ADV耐药性管理的共识。然而，很少关注一直集中在中ADV-ETV联合抢救治疗在临床上的延迟降低HBV DNA和ADV耐药变异动态。我们的特点病毒载量和抗性变异的动态，核苷（酸）类似物（NAS）-naïve慢性乙型肝炎（CHB）患者在与ADV单药治疗后跟ADV-ETV联合用药抗病毒治疗。

方法：对55例慢性乙型肝炎患者的队列被纳入研究。三NAS-初治患者在24-33个月的ADV单药治疗的开发ADV耐药变异，然后切换到ADV-ETV联合治疗。治疗期间定期收集从三个患者三十五个系列血清样本。与十大常用抗病毒药物相关的突变体是由焦磷酸测序法检测。

结果：HBV DNA降低到最低水平期间ADV单一疗法在6-18个月，以减少0.95-5.51 log10拷贝/毫升，而rtA181V或rtN236T延长治疗逐渐增加。 HBV DNA的减少到低于期间ADV-ETV组合疗法可检测的水平在21-24个月内，以减少4.19-4.65 log10拷贝/毫升。耐rtA181V和rtN236T为21-24个月的联合治疗后检测不到。此外，在27-36个月的联合治疗中没有检测到LAM耐药rtM204I / V或ETV抗性变体。

结论：虽然ADV耐药变异被抑制，病毒载量下降是在ADV-ETV联合抢救治疗的患者ADV耐药HBV延迟。耐药变异焦磷酸测序的量化可以方便监控抗病毒治疗。

关键词：阿德福韦，恩替卡韦，乙肝病毒，抢救治疗，抗

StephenW

http://www.medsci.org/v12p0416.htm

君看一叶舟

北京佑安医院和北京大学的研究成果，阿德耐药后，阿德联合恩替任然保持病毒下降的疗效，可以在治疗中量化检测