YMDD突变和拉米夫定耐药患者的乙型肝炎病毒的病毒准种可能

StephenW

Exp Ther Med. 2019 Apr;17(4):2473-2484. doi: 10.3892/etm.2019.7255. Epub 2019 Feb 11.
Viral quasispecies of hepatitis B virus in patients with YMDD mutation and lamivudine resistance may not predict the efficacy of lamivudine/adefovir rescue therapy.
Wang C1,2, Yu S1, Zhang Y1, Zhang M3, Lv L3, Huang C4, Li X1, Li J4, Zhang Z1,4.
Author information

1
    Department of Infectious Diseases, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230601, P.R. China.
2
    Department of Infectious Diseases, The Affiliated Anqing Hospital of Anhui Medical University, Anqing, Anhui 246000, P.R. China.
3
    Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
4
    College of Pharmacy, Anhui Medical University, Hefei, Anhui 230022, P.R. China.

Abstract

The association between hepatitis B virus (HBV) quasispecies (QS) and the efficacy of nucleos(t)ide analog therapy is currently not well defined, particularly in the case of lamivudine (LAM)/adefovir (ADV) combination rescue therapy for patients with chronic HBV infection (CHB) presenting with LAM resistance. In the present study, 16 CHB patients with the rtM204I/V mutation in the tyrosine-methionine-aspartate-aspartate motif of the C domain of the polymerase gene who switched to LAM/ADV treatment due to LAM resistance were assessed. HBV DNA was isolated from these patients and the reverse transcriptase (RT) region was sequenced. The QS heterogeneity and distribution was analyzed, the mutation sites were recorded and the phylogenetic trees were constructed. The results indicated that QS heterogeneity and distribution in the RT and S regions were not significantly different between responders (RS) and non-RS (NRS) at baseline (P>0.05), except for the higher frequency of a dominant strain in the RT region at the nucleotide level in the RS group (P=0.039). In addition, in NRS, no significant difference in QS heterogeneity or distribution in these regions was identified at six months vs. the baseline. Furthermore, although in the non-responder group the frequency of the LAM resistance-associated mutations (rtM204V/I) decreased at 6 months compared with the baseline, it did not disappear in any of the patients after six months of treatment. Analysis of individual patients did not indicate any consistent selection of specific HBV mutants during LAM/ADV rescue therapy. In conclusion, the baseline HBV QS within the RT and S regions may not be a valid predictor of the response to LAM/ADV rescue treatment in CHB patients with LAM resistance.
KEYWORDS:

adefovir; hepatitis B virus; lamivudine; quasispecies; resistance mutation

PMID:
    30906435
PMCID:
    PMC6425149
DOI:
    10.3892/etm.2019.7255

StephenW

Exp Ther Med。 2019年4月; 17（4）：2473-2484。 doi：10.3892 / etm.2019.7255。 Epub 2019年2月11日。
YMDD突变和拉米夫定耐药患者的乙型肝炎病毒的病毒准种可能无法预测拉米夫定/阿德福韦挽救疗法的疗效。
Wang C1,2，Yu S1，Zhang Y1，Zhang M3，Lv L3，Huang C4，Li X1，Li J4，Zhang Z1,4。
作者信息

1
    安徽医科大学第二附属医院感染科，安徽合肥230601，中国。
2
    安徽医科大学附属安庆医院感染科，安徽安庆246000，中国。
3
    安徽医科大学第一附属医院检验科，安徽合肥230022，中国。
4
    安徽医科大学药学院，安徽合肥230022，中国。

抽象

乙型肝炎病毒（HBV）准种（QS）与核效应（t）类似物治疗之间的关联目前尚未明确界定，尤其是拉米夫定（LAM）/阿德福韦（ADV）联合抢救治疗患者的情况。慢性HBV感染（CHB）表现出LAM抗性。在本研究中，评估了16名CHB患者，其在聚合酶基因的C结构域的酪氨酸 - 蛋氨酸 - 天冬氨酸 - 天冬氨酸基序中具有rtM204I / V突变，其由于LAM抗性而转换为LAM / ADV治疗。从这些患者中分离HBV DNA，并对逆转录酶（RT）区域进行测序。分析了QS的异质性和分布，记录了突变位点，构建了系统发育树。结果表明，RT和S区的QS异质性和分布在基线时响应者（RS）和非RS（NRS）之间没有显着差异（P> 0.05），除了RT中显性菌株的较高频率。 RS组核苷酸水平的区域（P = 0.039）。此外，在NRS中，与基线相比，在6个月时未发现这些区域的QS异质性或分布存在显着差异。此外，尽管在非应答者组中，与基线相比，LAM抗性相关突变（rtM204V / I）的频率在6个月时降低，但在治疗6个月后，其在任何患者中均未消失。对个体患者的分析未表明在LAM / ADV挽救治疗期间任何一致的特定HBV突变体的选择。总之，RT和S区内的基线HBV QS可能不是LAM抗性CHB患者对LAM / ADV抢救治疗反应的有效预测因子。
关键词：

阿德福韦;乙型肝炎病毒;拉米夫定;准种;抗性突变

结论：
    30906435
PMCID：
    PMC6425149
DOI：
    10.3892 / etm.2019.7255

StephenW

www.spandidos-publications.com/etm/17/4/2473/download