Molecular characterization of a novel entecavir mutation pattern isolated from a

StephenW

  http://www.sciencedirect.com/science/article/pii/S138665321100429X
Journal of Clinical Virology
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doi:10.1016/j.jcv.2011.10.011 | How to Cite or Link Using DOI

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Molecular characterization of a novel entecavir mutation pattern isolated from a multi-drug refractory patient with chronic hepatitis B infection
Ersin Karataylia, Senem C. Karataylia, Kubilay Cinarb, Selma Gokahmetogluc, Kadri Güvend, Ramazan Idilmanb, Cihan Yurdaydina, b, A. Mithat Bozdayia, b, ,

a	Ankara University, Institute of Hepatology, Ankara, Turkey

b	Ankara University, School of Medicine, Department of Gastroenterology, Ankara, Turkey

c	Erciyes University School of Medicine Department of Microbiology, Kayseri, Turkey

d	Erciyes University School of Medicine Department of Gastroenterology, Kayseri, Turkey

Received 11 August 2011; revised 14 October 2011; Accepted 18 October 2011. Available online 9 November 2011.


Abstract
Background

Prolonged antiviral treatment results in selection and accumulation of resistant strains in quasispecies pool in hepatitis B virus (HBV) infection.

Objectives

The aim of this study was to characterise a novel HBV pattern which shows resistance to lamivudine, adefovir dipivoxil and entecavir using in vitro phenoyping assay.

Study design

A male 36 years old patient diagnosed with anti HBe-positive chronic hepatitis B (CHB) had received lamivudine treatment for 7 years following an initial unsuccessfull interferon treatment. The therapy had been switched to adefovir and then to entecavir when breakthrough occcured during each treatment. This led only to a temporary HBV DNA decline which soon was followed by viral breakthrough despite the lack of known entecavir resistance mutations. Patient died after 9 months of entecavir treatment from liver failure. A total of 434 clones from 6 different serum samples were analysed retrospectively. HBV genomes bearing mutation patterns suggestive of antiviral resistance were analysed by in vitro phenotyping assay.

Results

Dominance of a clone carrying L80LV, L91I, M204I, S219A, N238D, Y245H changes was detected in the last serum sample of the patient just before his death. This pattern displayed 30.4 fold resistance to entecavir when compared with the wild type HBV by in vitro phenotyping assay.

Conclusion

A novel mutation pattern showing a high degree of resistance to entecavir was documented. In this pattern, the S219A and Y245H mutations mainly seem to contribute to the emergence of ETV resistance.

StephenW

摘要
背景

长期在在乙型肝炎病毒（HBV）感染的游泳池准种的选择和耐药菌株的积累的抗病毒治疗的结果。
目标

本研究的目的是描述一种新的HBV耐拉米夫定，阿德福韦和恩替卡韦体外phenoyping实验使用的模式显示。
研究设计

收到一位男36岁病人的诊断与抗HBe阳性的慢性乙型肝炎（CHB）拉米夫定治疗7年以下的初始干扰素治疗失败。该疗法已改用阿德福韦和恩替卡韦突破在每次治疗occcured时。这只会导致一个临时的HBV - DNA下降很快被病毒突破，尽管缺乏已知的恩替卡韦耐药突变。恩替卡韦治疗肝功能衰竭的9个月后，病人死亡。共有来自6个不同的血清标本434克隆进行回顾性分析。轴承暗示抗病毒药物耐药性的突变模式的乙肝病毒基因组进行了分析，在体外分型检测。
结果

携带L80LV，L91I，M204I，S219A，N238D克隆的领导地位，Y245H的变化是在病人的血清样品，只是生前的最后中检测到。这种模式显示30.4耐折恩替卡韦，与野生型HBV相比，在体外分型检测。
结论

一个新突变的格局，显示出高度的阻力恩替卡韦记录。在这种模式中，S219A和Y245H突变主要似乎有助于ETV耐药性的出现。

lyq2003526

文章引用了一个病例。 干扰失败 转拉米7年 耐药 ，再转阿德，再转恩替，最后肝功能衰竭 挂了。。

StephenW

回复 lyq2003526 的帖子

This is a warning that an accumulation of mutations can have serious adverse consequence. Therefore we should not use drugs with low resistance barriers.