Characterization of Hepatitis B Virus in Tenofovir-Treated and Untreated Chronically Infected Mothers and Their Immunoprophylaxis Failure Infants

Abstract

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 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.

Tenofovir alafenamide or tenofovir disoproxil fumarate in pregnancy to prevent HBV transmission: Maternal ALT trajectory and infant outcomes

“…In another study, we identified maternal genotype C and pre-S1 wild-type sequence to be potential risk factors for infant prophylaxis failure. 33 In a previous study, we found that 5.2% of newborns in the maternal TDF group had detectable HBV DNA at birth, but only 1.74% developed HBV infection. 30 This suggests that some infants might still be exposed to HBV from maternal blood, underscoring the importance of timely neonatal immunization and an appropriate host immune response to vaccines in effectively clearing the virus.…”

“…The potential causes of prevention failure include intrauterine infection, the child's own immunity (host factors), and viral factors. In another study, we identified maternal genotype C and pre‐S1 wild‐type sequence to be potential risk factors for infant prophylaxis failure 33 . In a previous study, we found that 5.2% of newborns in the maternal TDF group had detectable HBV DNA at birth, but only 1.74% developed HBV infection 30 .…”

Phenotypes of peripheral CD4+ T helper cell subsets in pregnant women with HBeAg-negative chronic asymptomatic HBV carriers

“…Chronic asymptomatic HBV carriers (ASCs) with HBeAg-negative are predominant among chronic ASCs, including women of childbearing age, and can also develop a potential risk of high morbidity due to HBV-related fatal liver diseases, mostly hepatocellular carcinoma and cirrhosis ( Kumar et al., 2009 ; Organization, 2016 ; Cui et al., 2022 ; Lian et al., 2022 ; Wang and Chen, 2022 ). Previous reports indicated that the levels of serum HBV-DNA, viral antigens (HBsAg, HBeAg) and ALT were mostly normal or stable in chronic ASCs with/without HBeAg-negative status, including pregnancy ( Cheung et al., 2021 ; Hsu et al., 2022 ; Wang et al., 2022 ). Our results showed that low HBV-DNA and ALT levels were not significantly different among HC, PW, and PW with HBeAg-negative ASCs.…”

Who Is at Risk for New Hepatitis B Infections Among People With HIV?

“…The HBV-specific medications TDF and TAF can reduce the risk of HBV infection and prevent transmission, as demonstrated with mother-to-child transmission [ 12 , 13 ]. In a recent retrospective analysis among MSM, TDF and TAF were found to reduce the risk of new HBV infection [ 14 ].…”