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孕妇中既往存在的乙肝病毒聚合酶突变的高流行率并不限制抗病毒治疗的疗效。

High Prevalence of Preexisting HBV Polymerase Mutations in Pregnant Women Does Not Limit the Antiviral Therapy Efficacy.

作者信息

Wang Jing, Liu Jinfeng, Yu Qiang, Jin Li, Yao Naijuan, Yang Yuan, Yan Taotao, Hu Chunhua, He Yingli, Zhao Yingren, Chen Tianyan, Zheng Jie

机构信息

Department of Rheumatology, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.

Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.

出版信息

Can J Infect Dis Med Microbiol. 2021 Apr 19;2021:6653546. doi: 10.1155/2021/6653546. eCollection 2021.

Abstract

BACKGROUND

HBV-resistant mutants in treatment-naïve patients may lead to antiviral treatment failure. It is not clear if HBV mutants are present in pregnant women and about the influence of the preexisting mutants on the short-term antiviral therapy during pregnancy.

METHOD

We enrolled 73 pregnant women with high HBV DNA load and telbivudine (TBV) treatment during pregnancy in this retrospective study. The UDPS was used to detect the HBV mutations before and after the TBV treatment.

RESULTS

Before TBV treatment, the complexity of HBV quasispecies of all subjects was 0.40 ± 0.09; 41.1% (30/73) and 53.4% (39/73) subjects had rtM204I/V and rtN236 T/A detected, respectively; and 9.6% (7/73) patients had more than 20% frequency mutation of rtM204I/V, which was also similar with high frequency of rtN236 T/A mutation (41.1% vs. 53.4%, =0.136; frequencies >20%: 9.6% vs. 5.5%, =0.347). After TBV treatment, 71.2% (52/73) subjects had HBV DNA load ≥ 10 IU/mL at delivery. Among them, 75.0% of patients with rtM204I positive had HBV DNA load ≥10 IU/mL at delivery, which was comparable with the subjects without rtM204I (75.0% vs. 70.8%, =0.710). No changes were found in the frequencies and the complexity of HBV quasispecies of rtM204I mutation after the TVB treatment.

CONCLUSION

The prevalence of preexisting drug-resistant mutations among pregnant women was high using UPDS. However, the preexisting HBV mutation had limited influence on the efficacy of short-term TBV treatment, and TBV treatment during late pregnancy seemed not to increase the risk of emerging HBV-resistant mutants.

摘要

背景

初治患者中的乙肝病毒(HBV)耐药突变可能导致抗病毒治疗失败。目前尚不清楚孕妇中是否存在HBV突变,以及既往存在的突变对孕期短期抗病毒治疗的影响。

方法

在这项回顾性研究中,我们纳入了73例孕期HBV DNA载量高且接受替比夫定(TBV)治疗的孕妇。采用超深度测序(UDPS)检测TBV治疗前后的HBV突变。

结果

TBV治疗前,所有受试者的HBV准种复杂性为0.40±0.09;分别有41.1%(30/73)和53.4%(39/73)的受试者检测到rtM204I/V和rtN236T/A;9.6%(7/73)的患者rtM204I/V突变频率超过20%,rtN236T/A突变频率也与之相似(41.1%对53.4%,P=0.136;频率>20%:9.6%对5.5%,P=0.347)。TBV治疗后,71.2%(52/73)的受试者在分娩时HBV DNA载量≥10 IU/mL。其中,rtM204I阳性患者中有75.0%在分娩时HBV DNA载量≥10 IU/mL,与无rtM204I的受试者相当(75.0%对70.8%,P=0.710)。TVB治疗后,rtM204I突变的HBV准种频率和复杂性未发现变化。

结论

使用超深度测序法发现孕妇中既往耐药突变的发生率较高。然而,既往存在的HBV突变对短期TBV治疗疗效的影响有限,妊娠晚期的TBV治疗似乎不会增加出现HBV耐药突变的风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afa8/8079218/e9bf0772223b/CJIDMM2021-6653546.001.jpg

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