对核苷/核苷酸类似物治疗中国慢性乙型肝炎患者乙肝病毒耐

StephenW

Profile of hepatitis B virus resistance mutations against nucleoside/nucleotide analogue treatment in Chinese patients with chronic hepatitis B

Jun Lei, Ying Wang, Li-Li Wang, Shao-Jun Zhang, Wei Chen, Zhi-Gang Bai and Lv-Ye Xu   

Jun Lei1
Email: [email protected]
Ying Wang1
Email: [email protected]
Li-Li Wang1
Email: [email protected]
Shao-Jun Zhang1
Email: [email protected]
Wei Chen1
Email: [email protected]
Zhi-Gang Bai1
Email: [email protected]
Lv-Ye Xu1*
* Corresponding author
Email: [email protected]
1 Department of Infectious Diseases, Wuhan Neurologist Hospital and General
Hospital of The Yangtze River Shipping, Wuhan, China
Virology Journal 2013, 10:313 doi:10.1186/1743-422X-10-313
Published: 25 October 2013
Abstract (provisional)

Aim: Antiviral drug-resistant HBV mutants are complex and currently partly understood. This study was performed to analyze the profile of hepatitis B virus (HBV) resistance mutations against nucleos(t)ide analogues (NAs) in patients with chronic hepatitis B (CHB).
Methods

This was a population-based cross-sectional study. Serum samples of 179 patients with virological breakthrough undergoing different NAs treatment were obtained between January 2008 and December 2012. The HBV reverse transcriptase region was sequenced and the following NAs-resistant changes including rtL80, rtI169, rtV173, rtL180, rtA181, rtT184, rtA194, rtS202, rtM204, rtN236 and rtM250 were analyzed.
Results

In this cohort, 21.2% (38/179) were genotypes B and 78.8% (141/179) were genotypes C; and 89.4% (160/179) of them detected NAs-resistant mutations. The prevalence of HBV mutations at rtM204 was 93.0% (106/114) in patients with lamivudine (LAM) or telbivudine (LdT)-based therapies, and that of rtN236 mutations was 76.1% (35/46) in patients with adefovir dipivoxil (ADV)-based therapies. Among LAM/LdT based therapies, HBV rtM204I was significantly associated with HBV rtL80I/V mutations [rtM204I+rtL80I/V (50.0%, 32/64) vs. rtM204V+rtL80I/V (27.3%,9/33), P=0.032]; while the HBV rtM204V mutations was significantly associated with HBV rtL180M mutations [rtM204V+rtL180M (100%, 33/33) vs. rtM204I+rtL180M (60.9%, 39/64), P<0.001]. Additionally, HBV rtA181 mutations were observed in 19.3% (22/114) of patients with LAM/LdT-based therapy and 23.9% (11/46) of patients with ADV-based therapy.
Conclusions

Majority of virological breakthrough is associated with NAs-resistant HBV, and the mutation patterns of NAs-resistant HBV are complicated in real clinical practice.

StephenW

雷军鹰王，王李，张韶君，魏晨，白智刚，徐吕晔

君磊
电子邮件： [email protected]
英Wang1
电子邮件： [email protected]
丽丽Wang1
电子邮件： [email protected]
邵俊张心
电子邮件： [email protected]
魏晨1
电子邮件： [email protected]的
志刚BAI1
电子邮件： [email protected]
吕叶旭*
*通讯作者
电子邮件： [email protected]
1传染科，武汉的神经学家医院和一般
医院，武汉，中国长江航运
病毒学杂志2013 ， 10:313 DOI ： 10.1186/1743-422X-10-313
发布时间： 2013年10月25日
摘要（临时）

目的：抗病毒药物耐药HBV突变是复杂的，目前部分的理解。这项研究对核苷（酸）类似物（NAS）在慢性乙型肝炎（ CHB ）患者进行分析B型肝炎病毒（HBV）耐药突变的档案。
方法

这是一个以人群为基础的横断面研究。血清样本179例接受不同NAS治疗的病毒学突破，获得2008年一月至2012年12月。 HBV逆转录酶区序列和分析包括以下NAS耐RTL80 rtI169 rtV173 rtL180 rtA181 rtT184 rtA194 rtS202 rtM204 rtN236和rtM250 。
结果

在这个群体中，21.2％ （38/ 179）基因型乙和78.8％ （141 / 179）的基因型Ç和89.4％ （160 /179） NAS耐药突变检测。 HBV突变rtM204的患病率分别为93.0％ （106/ 114）的患者与拉米夫定（ LAM ） ，替比夫定（LDT）为基础的疗法的rtN236突变率为76.1％ （35/ 46 ）患者用阿德福韦酯（ ADV）为基础的疗法。基于LAM / LDT的治疗方法当中， HBV rtM204I明显伴有HBV rtL80I / V突变[ rtM204I + rtL80I / V （ 50.0 ％， 32/64 ）与rtM204V + rtL80I / V （27.3％ ， 9 /33） ，P = 0.032 ] ，而HBV rtM204V突变明显伴有HBV为rtL180M突变[ rtM204V +为rtL180M （100％， 33/33 ）与rtM204I +为rtL180M （60.9 ％ ，39/ 64 ） ，P < 0.001 ]。此外，观察在基于LAM / LDT治疗和ADV为基础的治疗的患者的23.9％ （11 /46）的患者的19.3％ （22 /114） ， HBV rtA181突变。
结论

病毒学突破多数是与NAS-抗HBV ，和NAS-抗HBV的突变模式在实际临床实践中复杂。