在核心启动子/前核苷酸在核心（t）ide治疗的前12周期间的核

StephenW

Infect Genet Evol. 2017 Jan 11. pii: S1567-1348(17)30012-6. doi: 10.1016/j.meegid.2017.01.009. [Epub ahead of print]
The nucleotide changes within HBV core promoter/precore during the first 12weeks of nucleos(t)ide treatment might be associated with a better virological response.Peng Y1, Li Y2, Hou J3, Sun J3, Su M2, Li Y2, Xiang K2, Yan L2, Zhuang H2, Li T4.
Author information

• 1Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; Department of Clinical Laboratory, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
• 2Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
• 3Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
• 4Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China. Electronic address: [email protected].
  

AbstractOBJECTIVES: We aimed to study the dynamic changes of hepatitis B virus (HBV) core promoter/precore (CP/preC) sequences during antiviral treatment and their associations with virological responses.
MATERIALS AND METHODS: The baseline and 12-week CP/preC sequences (nts 1655-2014) were obtained from 52 chronic hepatitis B patients with positive hepatitis B e antigen (HBeAg), who received a 104-week lamivudine and adefovir dipivoxil combination therapy. The mutations within the CP/preC were analyzed against genotype specific reference sequences. The nucleotide change rates in individuals during therapy were analyzed in a pairwise comparison manner.
RESULTS: There was no significant difference of the mutation rate at each nucleotide site between baseline and week 12 of treatment (P>0.05). The mutation rates of A1762T/G1764A and G1896A were found to decrease from 46.2% (24/52) at baseline to 36.5% (19/52) at week 12 (P=0.426) and from 28.8% (15/52) to 21.2% (11/52) (P=0.497), respectively. The nucleotide change rates varied from 0.0% - 7.8% in individuals [0.0% in Group 1 (N=26); 0.3% - 7.8% in Group 2 (N=26)] during the first 12-week treatment. HBV DNA levels in group 2 were significantly lower than those in group 1 throughout therapy (P<0.01) (e.g., 1.5±1.3log10 IU/ml vs. 2.6±1.0log10 IU/ml at week 104, P=0.001). At week 104 the rates of HBV DNA undetectable and HBeAg loss in group 2 were significantly higher than those in group 1 (P<0.05). Along with the increased nucleotide change rates, the rate of HBV DNA undetectable at week 104 tended to increase (odds ratio=0.323, 95% confidence interval=0.138-0.758, P<0.001).
CONCLUSION: Our findings suggested that the nucleotide changes within HBV CP/preC region during the first 12-week treatment might be associated with a better virological response.

Copyright © 2016. Published by Elsevier B.V.

KEYWORDS: Antiviral response; Core promoter; Hepatitis B virus; Mutation; Nucleotide change; Precore

PMID:28088502DOI:10.1016/j.meegid.2017.01.009

StephenW

感染Genet Evol。 2017 Jan 11. pii：S1567-1348（17）30012-6。 Doi：10.1016 / j.meegid.2017.01.009。 [打印前的电子版]
在核心启动子/前核苷酸在核心（t）ide治疗的前12周期间的核苷酸变化可能与更好的病毒学反应相关联。
Peng Y1，Li Y2，Hou J3，Sun J3，Su M2，Li Y2，Xiang K2，Yan L2，Zhuang H2，Li T4。
作者信息

北京大学基础医学院微生物与传染病中心北京大学健康科学中心北京100191;中山大学第一附属医院临床实验室广州510080。
北京大学基础医学院微生物与传染病中心北京大学健康科学中心北京100191。
南方医科大学南方医院传染病与肝病科，广州510515。
4北京大学健康科学中心基础医学科微生物与传染病中心北京100191。电子地址：[email protected]。

抽象
目标：

我们的目的是研究乙型肝炎病毒（HBV）核心启动子/前核（CP / preC）序列在抗病毒治疗期间的动态变化及其与病毒学应答的关联。
材料和方法：

基线和12周CP / preC序列（nts 1655-2014）获自52位接受104周拉米夫定和阿德福韦酯联合治疗的乙型肝炎阳性抗原（HBeAg）的52名慢性乙型肝炎患者。针对基因型特异性参考序列分析CPC / preC。以成对比较方式分析治疗期间个体的核苷酸变化率。
结果：

发现A1762T / G1764A和G1896A的突变率从基线时的46.2％（24/52）降至治疗的第12周（P> 0.05）。在治疗的基线和第12周之间，在每个核苷酸位点的突变率没有显着差异（P = 0.497）。核苷酸变化率在0.0％至7.8％（15/52）至21.2％（11/52）％之间变化。在个体中[组1中的0.0％（N = 26）在第2组（N = 26）中为0.3％-7.8％]。在治疗期间（例如，1.5±1.3log 10 IU / ml相对于在104周时为2.6±1.0log 10 IU / ml，P = 0.001），组2中的HBV DNA水平显着低于组1中的那些。在第104周，第2组中HBV DNA不可检测和HBeAg丢失的速率显着高于第1组（P <0.05）。随着核苷酸变化率的增加，在第104周时不可检测的HBV DNA的速率趋于增加（优势比= 0.323,95％置信区间= 0.138-0.758，P <0.001）。
结论：

我们的研究结果表明，在前12周治疗期间HBV CP / preC区域内的核苷酸变化可能与更好的病毒学应答相关。

版权所有©2016 Elsevier B.V.出版
关键词：

抗病毒反应;核心启动子;乙型肝炎病毒;突变;核苷酸变化; Precore

PMID：
28088502
DOI：
10.1016 / j.meegid.2017.01.009