EASL 2013:乙肝病毒准种和逆转录变种对恩替治疗的反应

StephenW

Abstract 779
     
EFFECTS OF HEPATITIS B VIRUS QUASISPECIES AND REVERSE TRANSCRIPTASE VARIANTS ON TREATMENT RESPONSIVENESS TO ENTECAVIR   

D. Wong1,2*, M. Kopaniszen1, J. Fung1,2, W.-K. Seto1, F.-Y. Huang1, C.-L. Lai1,2, M.-F. Yuen1,2
1Medicine, 2State Key Laboratory for Liver Research, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong S.A.R.. *[email protected]

Background and aims: Entecavir therapy reduces hepatitis B virus (HBV) DNA to an undetectable level in around 60 - 80 % of patients after 1 year of treatment, but HBV DNA may remain detectable in the remaining patients. We aimed to determine whether baseline HBV reverse transcriptase (rt) sequence polymorphisms and quasispecies complexity and diversity are associated with the differences in treatment response.
Methods: Pre-treatment HBV rt sequence from 305 entecavir-treated patients were determined by DNA sequencing. Sequencing data were associated with their virological outcome, as defined by optimal response (undetectable HBV DNA at year 1) or partial response (HBV DNA >60 copies/mL). Quasispecies complexity and diversity were determined using MEGA 5.0 software.
Results: Seventeen rt variants were more frequently detected in the partial responders (n = 64; 21%) than in the optimal responders (all P < 0.05). Multivariate analysis revealed that high baseline HBV DNA, hepatitis B e antigen (HBeAg)-positivity and rt124N were associated with partial entecavir response. Compared with the partial responders, the optimal responders had a higher quasispecies complexity at nucleotide and amino acid levels (P = 0.036 and 0.087, respectively) and higher quasispecies diversity, as reflected by a greater genetic distance at both nucleotide and amino acid levels (P = 0.019 and 0.032, respectively) and a greater number of synonymous substitutions per synonymous site (dS; P = 0.015) and number of non-synonymous substitutions per non-synonymous site (dN; P = 0.039).
Conclusions: High baseline HBV DNA, HBeAg-positivity and rt124N were associated with partial entecavir response at year 1. Baseline HBV quasispecies complexity and diversity were higher in the optimal responders than in the partial responders.


Assigned speakers:
Dr. Danny Wong, The University of Hong Kong, Queen Mary Hospital , Hong Kong , Hong Kong S.A.R.

Assigned in sessions:
26.04.2013, 09:00-18:00, Poster Session, P02-07c, Category 07c: Viral Hepatitis B & D: Clinical (therapy, new compounds, resistance), Poster Area

StephenW

背景和目的：降低恩替卡韦治疗乙型肝炎病毒（HBV）DNA检测不到的水平在大约60  -  80％的患者治疗1年后，但在余下的患者HBV DNA仍然检测。我们的目的是，以确定是否：基线HBV逆转录酶（RT）序列多态性和治疗反应的差异相关联的准种的复杂性和多样性。
通过DNA测序方法：从305恩替卡韦治疗的患者治疗前HBV RT序列测定。测序数据都与他们的病毒学结果，所定义的最佳响应（在1年不到HBV DNA）或部分缓解（HBV DNA> 60拷贝/ ml）。准种的复杂性和多样性的确定，采用MEGA 5.0软件。
结果：十七RT变种更频繁地检测部分应答组（n = 64，21％）比在最佳反应者（均P <0.05）。多因素分析显示，高基线HBV DNA，乙肝e抗原（HBeAg）阳性阳性和rt124N伴有局部恩替卡韦响应。的最佳反应的部分反应者相比，有较高的准种的复杂性在核苷酸和氨基酸水平（P = 0.036和0.087，分别）和更高的准种的多样性，所反映的更大的遗传距离在核苷酸和氨基酸水平（P分别= 0.019和0.032）和更大数量的每同义位点的同义替换（dS的，P = 0.015）和数量的每个非同义位点的非同义替换（dN的，P = 0.039）。
结论：高基线HBV DNA，e抗原阳性和rt124N在今年1伴有局部恩替卡韦响应。基线HBV准种的复杂性和多样性均高于最佳反应比部分应答。