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学科主题: 基础医学
题名:
Profile of HBV antiviral resistance mutations with distinct evolutionary pathways against nucleoside/nucleotide analogue treatment among Chinese chronic hepatitis B patients
作者: Yang, Jing-Xian1; Liu, Bao-Ming1; Li, Xiao-Guang2; Yan, Chun-Hui1; Xu, Jie2; Sun, Xie-Wen3; Wang, Yu-Hua3; Jiao, Xiu-Juan3; Yan, Ling1; Dong, Jan-Ping4; Hou, Chun-Sheng5; Abuduheilili, Xiernayi6; Li, Tong1; Zhuang, Hui1
刊名: ANTIVIRAL THERAPY
发表日期: 2010
DOI: 10.3851/IMP1677
卷: 15, 期:8, 页:1171-1178
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Infectious Diseases ; Pharmacology & Pharmacy ; Virology
研究领域[WOS]: Infectious Diseases ; Pharmacology & Pharmacy ; Virology
关键词[WOS]: ADEFOVIR DIPIVOXIL ; ENTECAVIR RESISTANCE ; VIRUS POLYMERASE ; DRUG-RESISTANCE ; TREATMENT FAILURE ; IN-VITRO ; LAMIVUDINE ; TENOFOVIR ; THERAPY ; SUBSTITUTIONS
英文摘要:

Background: Antiviral drug-resistant HBV mutants under a variety of treatment protocols are complex and only partly understood. Here, a population-based cross-sectional study was performed to analyse the profile of resistance mutations in distinct evolutionary pathways refractory to different nucleoside/nucleotide analogues (NAs).

Methods: Serum samples of 199 chronic hepatitis B patients undergoing NA treatment from five hospitals in four northern cities of China were obtained between January 2007 and July 2009. The genotypic resistance of HBV in these samples was characterized. The full-length HBV reverse transcriptase region was amplified, sequenced and analysed with particular focus on the following NA-resistant changes: rtL80, rtI169, rtV173, rtL180, rtA181, rtT184, rtA194, rtS202, rtM204, rtN236 and rtM250.

Results: Among 199 HBV isolates, 30 (15.08%) and 169 (84.92%) were genotypes B and C, respectively, and 65 (32.66%) harboured NA-resistant mutations. The prevalence of mutations at rtM204 was 34.33% in 134 patients who had received or who had been exposed to lamivudine-based therapy. Five cases of rtN236 mutations were detected exclusively among 75 patients receiving adefovir-dipivoxil-based therapies. A total of 19 cases of multidrug resistance rtA181 mutations were observed in those with lamivudine-, adefovir-dipivoxil-or telbivudine-based treatment (186 cases), but not in those undergoing entecavir treatment (13 cases). Mutations were not found at rtI169, rtT184, rtA194 or rtS202. rtM204 mutations (27 rtM204I, 15 rtM204V and 5 rtM204I/V cases) were detected at the highest frequency among 65 mutants (72.30% [47/65]) and found to display 16 combination mutation patterns, in which rtM204I and rtM204V were significantly associated with rtL80I/V and rtL180M, respectively (P<0.01).

Conclusions: One-third of the studied population harboured NA-resistant HBV with complicated mutation patterns. Monitoring HBV genotypic resistance mutation markers and patterns is therefore shown to be beneficial for optimizing antiviral therapies and for avoiding clinical deterioration.

语种: 英语
所属项目编号: 2005CB523104 ; 2008ZX10002-004 ; 2009ZX10004-314
项目资助者: Chinese National Key Basic Research Project ; Major Science and Technology Special Project of China Eleventh Five-year Plan
WOS记录号: WOS:000287431200012
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/67694
Appears in Collections:基础医学院_病原生物学系_期刊论文

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作者单位: 1.Qinhuangdao Third Hosp, Dept Infect Dis, Qinhuangdao, Peoples R China
2.Beijing Haidian Hosp, Dept Infect Dis, Beijing, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Dept Microbiol, Beijing 100871, Peoples R China
4.Peking Univ, Hosp 3, Dept Infect Dis, Beijing 100871, Peoples R China
5.Shandong Jining Infect Dis Hosp, Dept Infect Dis, Jining, Peoples R China
6.Xinjiang Med Univ, Affiliated Hosp 1, Dept Infect Dis, Urumqi, Peoples R China

Recommended Citation:
Yang, Jing-Xian,Liu, Bao-Ming,Li, Xiao-Guang,et al. Profile of HBV antiviral resistance mutations with distinct evolutionary pathways against nucleoside/nucleotide analogue treatment among Chinese chronic hepatitis B patients[J]. ANTIVIRAL THERAPY,2010,15(8):1171-1178.
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