替诺福韦治疗和未治疗的慢性感染母亲及其免疫预防失败婴

StephenW

替诺福韦治疗和未治疗的慢性感染母亲及其免疫预防失败婴儿中乙型肝炎病毒的特征
Hong Yuan Hsu, Huey Ling Chen, Cheng Lun Chiang, Ming Wei Lai, Shu Chi Mu, Wan Hsin Wen, Shao Wen Cheng, Jen Jan Hu, Kai Chi Chang, Chien Nan Lee ... 显示更多
临床传染病，ciac539，https://doi.org/10.1093/cid/ciac539
发表：
2022 年 7 月 5 日
摘要
背景

孕晚期母体富马酸替诺福韦酯 (TDF) 治疗可减少乙型肝炎病毒 (HBV) 的母婴传播。我们调查了与母体 TDF 治疗相关的 HBV 突变及其在婴儿免疫预防失败 (IPF) 中的作用。
方法

通过巢式 PCR 和直接测序分析来自未处理 (n = 89) 和 TDF 处理 (n = 68)、高度病毒血症、慢性感染的母亲及其婴儿的血清样本的 HBV DNA。
结果

在分娩时，与未接受治疗的母亲相比，接受 TDF 治疗的母亲的 HBV DNA 滴度较低，基础核心启动子 (BCP) 基因突变的频率较高，但她们在 pre-S/S 和 pre-core/core 突变中的频率相似.携带表面“a”决定簇突变体的 14 名母亲没有将突变体传播给她们的免疫婴儿。在 13 名 IPF 婴儿中的 3 名中发现了这种突变体。 13 名母亲为野生型 HBsAg。在单变量分析中，母体 HBV DNA 滴度（优势比 [OR]：1.54；95% 置信区间 [CI]：1.02∼2.33；P = 0.039），基因型 C（OR：4.18；95% CI：1.28∼13.62；P = 0.018）和 pre-S1 野生型序列（OR：6.33；95% CI：1.85∼21.68；P = 0.003）与婴儿 IPF 相关。多变量分析显示母体基因型 C (OR: 3.71; 95% CI: 1.11-12.36; P = 0.033) 和 pre-S1 野生型 (OR: 6.34; 95% CI: 1.79-22.44; P = 0.004) 相关与母体病毒血症无关的婴儿 IPF。
结论

结论

除了分娩时高母体 HBV DNA 滴度外，母体基因型 C 和 pre-S1 野生型序列是婴儿 IPF 的潜在危险因素，而 BCP 突变则不是。携带“a”行列式突变体作为主要菌株的孕妇的后代似乎受到免疫预防的保护。

StephenW

Characterization of Hepatitis B Virus in Tenofovir-Treated and Untreated Chronically Infected Mothers and Their Immunoprophylaxis Failure Infants
Hong Yuan Hsu, Huey Ling Chen, Cheng Lun Chiang, Ming Wei Lai, Shu Chi Mu, Wan Hsin Wen, Shao Wen Cheng, Jen Jan Hu, Kai Chi Chang, Chien Nan Lee ... Show more
Clinical Infectious Diseases, ciac539, https://doi.org/10.1093/cid/ciac539
Published:
05 July 2022
Abstracts
Background

Maternal tenofovir disoproxil fumarate (TDF) therapy during late pregnancy can reduce mother-to-infant transmission of hepatitis B virus (HBV). We investigated HBV mutations associated with maternal TDF therapy and their role in infant immunonophylaxis failure (IPF).
Methods

Serum samples from untreated (n = 89) and TDF-treated (n = 68), highly-viremic, chronically infected mothers and their infants were analyzed for HBV DNA by nested-PCR and direct sequencing.
Results

At delivery, compared with untreated mothers, TDF-treated mothers had a lower HBV DNA titer and a higher frequency of basal core promoter (BCP) gene mutations, but they had similar frequencies in pre-S/S and pre-core/core mutations. The 14 mothers harboring surface “a” determinant mutants did not transmit the mutants to their immunized infants. Such mutants were found in 3 of 13 IPF infants; the 13 mothers had wild-type HBsAg. In univariable analysis, maternal HBV DNA titer (odds ratio [OR]: 1.54; 95% confidence intervals [CI]:1.02∼2.33; P = 0.039), genotype C (OR: 4.18; 95% CI: 1.28∼13.62; P = 0.018) and pre-S1 wild-type sequence (OR: 6.33; 95% CI: 1.85∼21.68; P = 0.003) at delivery were associated with infant IPF. Multivariable analyses showed that maternal genotype C (OR: 3.71; 95% CI: 1.11-12.36; P = 0.033) and pre-S1 wild-type (OR: 6.34; 95% CI: 1.79-22.44; P = 0.004) were associated with infant IPF independently of maternal viremia.
Conclusions

Conclusions

Along with high maternal HBV DNA titer at delivery, maternal genotype C and pre-S1 wild-type sequence were potential risk factors for infant IPF, while BCP mutations were not. The offspring of pregnant women harboring “a” determinant mutants as major strains seemed to be protected by immunoprophylaxis.