HBV-infected Pregnant Women Research Articles

Association of hepatitis B virus and thyroid hormones during pregnancy.

This study aims to evaluate the correlation between serum thyroid hormone levels and hepatitis B virus (HBV) DNA and HBV genotypes in pregnant women with chronic hepatitis B. A total of 96 pregnant women with chronic HBV-infected pregnant women between January 2020 and December 2022 were selected as the observational study subjects. About 50 HBV-uninfected pregnant women during the same period were selected as the control group. Serum thyroid hormone levels at different stages of pregnancy, including free triiodothyronine (FT3), free thyroxine (FT4), thyroid stimulating hormone (TSH), thyroperoxidase antibody (TPOAb), and thyroglobulin antibody (TGAb), were compared between the 2 groups. Thyroid hormones levels were also compared between HBV-DNA-positive and HBV-DNA-negative women in the HBV-infected pregnancy group, and to determine the correlation between thyroid hormones levels and HBV-DNA load and HBV genotype in HBV-DNA-positive pregnant women. The TSH levels in mid and late pregnancy and TPOAb levels in early, mid, and late pregnancy of HBV-infected pregnant women were higher than those in the same period in HBV-uninfected pregnant women (P < .05). The TPOAb and TGAb levels in early, mid, and late pregnancy of HBV-DNA-positive pregnant women were higher than those in the same period in HBV-DNA-negative pregnant women (P < .05). The HBV-DNA load and FT3 or FT4 levels were negatively correlated (P < .05), and the HBV-DNA load and TGAb levels were positively correlated (P < .05). However, there was no statistical difference in thyroid hormone levels between different HBV genotypes (P > .05). The thyroid hormone levels will change in pregnant women infected with hepatitis B virus, and there is a certain correlation between HBV-DNA load and thyroid hormone levels. Therefore, timely monitoring of thyroid hormones and HBV-DNA load can provide early prevention and treatment for HBV infection in pregnant women, ensuring the health of pregnant women and fetuses.

The effect of intrahepatic cholestasis in pregnancy combined with different stages of hepatitis B virus infection on pregnancy outcomes: a retrospective study.

To investigate the impact of intrahepatic cholestasis of pregnancy (ICP) with hepatitis B virus (HBV) infection on pregnancy outcomes. We selected 512 pregnant women, collected the data including maternal demographics, main adverse pregnancy outcomes and maternal HBV infected markers HBeAg and HBV-DNA loads status, then have a comparative analysis. There were 319 solitary ICP patients without HBV infection (Group I) and 193 ICP patients with HBV infection. Of the latter, there were 118 cases with abnormal liver function(Group II) and 80 cases with normal liver function(Group III). All HBV-infected pregnant women with ICP were divided into hepatitis Be antigen (HBeAg)-positive group (102 cases) and HBeAg-negative group (91 cases), according to the level of the serum HBeAg status; and into high viral load group (92 cases), moderate viral load group (46 cases) and low viral load group (55 cases) according to the maternal HBV-DNA level. Group II had a higher level of serum total bile acids, transaminase, bilirubin as well as a higher percentage of premature delivery, neonatal intensive care unit (NICU) admission and meconium-stained amniotic fluid (MSAF) compared with the other two groups(P < 0.05), but there were no significant differences in the above indicators between the Group I and Group III. Among the HBV-infected patients with ICP, HBeAg-positive group had a higher level of serum transaminase, bilirubin and bile acid as well as earlier gestational weeks of delivery, lower birth weight of new-borns and a higher rate of NICU admission than HBeAg-negative group (P < 0.05). Those with a high viral load (HBV-DNA > 106IU/ml) had a higher level of transaminase, bilirubin, and bile acid as well as shorter gestational weeks of delivery, lower birth weight of new-borns and a higher rate of NICU admission compared with those with a low or moderate viral load (P < 0.05). HBV-infected pregnant women with ICP combined with abnormal liver function have more severe liver damage, a higher percentage of preterm birth and NICU admission. HBeAg-positive status and a high HBV-DNA load will increase the severity of conditions in HBV-infected pregnant women with ICP. HBV-infected patients with ICP who have abnormal liver function, HBeAg-positive or a high viral load should be treated more actively.

Altered TLR7 Expression-Mediated Immune Modulation Is Supportive of Persistent Replication and Intrauterine Transmission of HBV.

Hepatitis B Virus (HBV) is posing as a serious public health threat mainly due to its asymptomatic nature of infection in pregnancy and vertical transmission. Viral sensing toll-like receptors (TLR) and Interleukins (IL) are important molecules in providing an antiviral state. The study aimed to assess the role of TLR7-mediated immune modulation, which might have an impact in the intrauterine transmission of HBV leading to mother to child transmission of the virus. We investigated the expression pattern of TLR7, IL-3, and IL-6 by RT-PCR in the placentas of HBV-infected pregnant women to see their role in the intrauterine transmission of HBV. We further validated the expression of TLR7 in placentas using Immunohistochemistry. Expression analysis by RT-PCR of TLR7 revealed significant downregulation among the Cord blood (CB) HBV DNA positive and negative cases with mean ± standard deviation (SD) of 0.43 ± 0.22 (28) and 1.14 ± 0.57 (44) with p = 0.001. IL-3 and IL-6 expression revealed significant upregulation in the CB HBV DNA-positive cases with p = 0.001. Multinomial logistic regression analysis revealed that TLR7 and IL-3 fold change and mother HBeAg status are important predictors for HBV mother to child transmission. Immunohistochemistry revealed the decreased expression of TLR7 in CB HBV DNA-positive cases. This study reveals that the downregulation of TLR7 in the placenta along with CB HBV DNA-positive status may lead to intrauterine transmission of HBV, which may lead to vertical transmission of HBV.

Mother-to-Child Transmission of HBV Infection by Preventive Interventions in Southern Vietnam's Hospitals.

The World Health Organization (WHO) recommends tenofovir disoproxil fumarate (TDF) for pregnant women with hepatitis B virus (HBV) presenting with HBV DNA levels of 106 copies/mL or more to hinder mother-to-child transmission (MTCT). Moreover, it is suggested that neonates of HBV-infected mothers receive an HBV vaccine birth dose within 24 hours of birth to mitigate transmission risk. The study included 661 HBV-infected pregnant women and 316 infants from 3 hospitals in Southern Vietnam between October 2019 and November 2020. Infants were classified on the basis of their mothers' TDF prophylaxis into I-TDF (+) group (107 infants) whose mothers received TDF; I-TDF (-) group (56 infants) whose mothers missed TDF; and I-NTDF group (153 infants) whose mothers did not necessitate TDF. Almost all infants received an HBV vaccine birth dose with HBIG administered on the basis of parents' financial standing. MTCT was found in 2.2% of the cases. The respective MTCT rates for I-TDF (+), I-TDF (-), and I-NTDF groups were 2.8%, 5.4%, and 0.7%. Immune response rates to the HBV vaccination in the total cohort, I-TDF (+), I-TDF (-), and I-NTDF groups, were 88.6%, 87.9%, 85.7%, and 90.2%, respectively. Vaccinated infants exhibited a statistically lower risk of HBV infection postbirth (aRR = 0.1; 95% confidence interval, 0.0-0.6; P = .01). TDF can equate the MTCT risk in pregnant women with HBV DNA levels of 106 copies/mL or more to those with lower levels. Early administration of the HBV vaccine postbirth also effectively curtails MTCT. Thus, expanding TDF prophylaxis and vaccine coverage is pivotal to impede MTCT.

Comparison of the efficacy and safety of TAF, TDF, and LdT to prevent the transmission of hepatitis B in pregnant women: A retrospective study.

To compare the efficacy and safety of telbivudine (LdT), tenofovir alafenamide fumarate (TAF), and tenofovir disoproxil fumarate (TDF) for preventing hepatitis B transmission in immune-tolerant pregnant women with HBV infection. We conducted a retrospective cohort study involving women who had hepatitis B virus deoxyribonucleic acid (HBV DNA) ≥ 2 × 105 IU/mLand initiated LdT, TDF, or TAF to prevent mother-to-child transmission (MTCT). The primary endpoint was the safety of mothers and infants. The secondary endpoints were maternal HBV DNAreduction at delivery and MTCT rate. A total of 96 patients were enrolled in the study (LdT group, n = 36; TDF group, n = 35; TAF group, n = 25). All infants received hepatitis B virus immunoprophylaxis. The MTCT rate was 0%([0 of 25] vs. [0 of 35] vs. [0 of 36], p > .05). No severe liver function damage occurred in any of the mothers. Babies delivered in all groups had prenatal ultrasound screening abnormalities, but abnormality rates were not statistically significant between groups. The application of TDF, TAF, or LdT to immune-tolerant HBV-infected pregnant women in middle-late pregnancycan successfully interrupt MTCT of the HBV virus. However, for all three groups of pregnant women who delivered babies with abnormal prenatal ultrasound screening, an expanded sample size may be needed for further observation.

Real-world implementation of a multilevel interventions program to prevent mother-to-child transmission of HBV in China.

Reducing hepatitis B virus (HBV) mother-to-child transmission (MTCT) is a fundamental step toward the HBV elimination goal. The multicentred, multilevel SHIELD program aimed to use an intense intervention package to reduce HBV MTCT in China. This study was conducted in diverse health settings across China, encompassing 30,109 pregnant women from 178 hospitals, part of the interim analysis of stage II of the SHIELD program, and 8,642 pregnant women from 160 community-level health facilities in stage III of the SHIELD program. The study found that the overall MTCT rate was 0.23% (39 of 16,908; 95% confidence interval (CI): 0.16-0.32%) in stage II and 0.23% (12 of 5,290; 95% CI: 0.12-0.40%) in stage III. The MTCT rate was lower among participants who were compliant with the interventions (stage II: 0.16% (95% CI: 0.10-0.26%); stage III: 0.03% (95% CI: 0.00-0.19%)) than among those who were noncompliant (3.16% (95% CI: 1.94-4.85%); 1.91% (95% CI: 0.83-3.73%); P < 0.001). Our findings demonstrate that the comprehensive interventions among HBV-infected pregnant women were feasible and effective in dramatically reducing MTCT.

Simplified Criteria to Assess Long-Term Antiviral Treatment Indication in Chronic HBV-Infected Pregnant Women in Cambodia.

Pregnant women identified to carry hepatitis B surface antigen (HBsAg) should be linked to care for the determination of the need for long-term antiviral therapy (LTT). We assessed the performance of simplified criteria, free from HBV DNA quantification, to select women eligible for LTT using different international guidelines as a reference. A retrospective analysis of HBV-infected pregnant women enrolled in the phase 4 ANRS TA-PROHM study was conducted in Cambodia. Sensitivity, specificity, and AUROC were computed to compare three simplified criteria (TREAT-B, HBcrAg/ALT, and TA-PROHM) with the American (AASLD) and European (EASL) guidelines as a reference. An additional assessment was performed at 6 months postpartum. Of 651 HBsAg-positive women, 209 (32%) received peripartum antiviral prophylaxis using tenofovir disoproxil fumarate (TDF). During pregnancy, 9% and 12% of women were eligible for LTT according to AASLD and EASL guidelines, respectively; 21% and 24% of women were eligible for prophylactic TDF and 2% and 5% in those ineligible (p < 0.001). Using the AASLD guidelines, the AUROC of TREAT-B, HBcrAg/ALT, and TA-PROHM scores were 0.88 (95%CI, 0.85-0.90), 0.90 (95%CI, 0.87-0.92), and 0.76 (95%CI, 0.73-0.80), respectively. Using the EASL guidelines, the AUROCs were lower: 0.73 (95%CI, 0.69-0.76), 0.76 (95%CI, 0.73-0.80), and 0.71 (95%CI, 0.67-0.74), respectively. Among those ineligible for prophylactic TDF, only 2% to 6% present an indication for LTT at 24 weeks postpartum. Few pregnant women are eligible for LTT, and the use of simplified criteria could represent an efficient triage option in decentralized areas to identify those negative for whom there is no urgent indication for LTT and focus on those positive for whom other exams must be conducted to confirm LTT indication.

Hepatitis B virus genotypes associated with pregnant women in Northern Thailand

BackgroundMother-to-child transmission of hepatitis B virus (HBV) is the major route of transmission causing persistent infection. The prevalence of HBV infection and HBV genotypes found in different geographical areas varies from country to country. Therefore, this study was conducted to identify the HBV genotypes in HBV-infected pregnant women in Northern Thailand. MethodsStored blood samples that were collected from 145 HBsAg-positive pregnant women who gave birth at Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand from 2017 to 2020 were analyzed. The partial nucleotide sequence of the S gene of HBV was amplified by nested PCR and sequenced. All sequences were analyzed phylogenetically together with the reference strains to define the HBV genotypes. ResultsA total of 31 blood samples from 145 HBsAg-positive pregnant women were positive for HBV by nested PCR. The detected HBV strains were identified as presumptive subgenotypes C1 (77.4%; 24/31), B9 (9.7%; 3/31), C2 (3.2%; 1/31), B2 (3.2%; 1/31), B4 (3.2%; 1/31), and presumptive B4/C2 recombinant subgenotype (3.2%; 1/31). ConclusionsThe findings revealed that presumptive subgenotype C1 was the most common subgenotype circulating in pregnant women in Northern Thailand and accounted for 77.4% of cases, followed by presumptive subgenotypes B9, C2, B2, and B4. Furthermore, this study reported, for the first time in Thailand, the HBV genotypes and presumptive subgenotypes, particularly subgenotype B9 circulating in pregnant women.

'We are willing, but we have challenges': Qualitative enquiry on midwives' views on factors influencing the prevention of mother-to-child transmission of hepatitis B program.

Mother-to-child transmission of hepatitis B infection is one of the major routes of hepatitis B virus (HBV) infection in Africa. Amusingly, Africa is the only region yet to meet the World Health Organization's target of reducing the prevalence of HBV infection to less than 1% among children under 5 years of age by 2020. In Ghana, little has been documented about midwives' views on the factors impacting the successful implementation of mother-to-child transmission via HBV prevention programs. This study explored midwives' views on the challenges associated with the prevention of mother-to-child transmission of HBV infection in the La-Nkwantanang municipality. The study adopted an exploratory descriptive qualitative design and involved 14 midwives who were purposively recruited from a primary-level health facility in the La-Nkwantanang Municipality, Accra. Individual face-to-face interviews were conducted using an in-depth interview guide. The data were content analyzed using the six steps recommended by Braun and Clark. Three main themes, namely, health professional or midwife factors and patient and health facility factors, negatively impacted the prevention of maternal-to-child transmission program. The five subthemes identified in this study included lack of awareness, financial constraints, and unavailability of logistics and protocols. The study recognized that midwives face many challenges even though they have a strong desire to prevent vertical transmission of HBV. The implementation of a mother-to-child transmission program is negatively impacted by many intrinsic, client, and health facility factors. Midwives who act as major stakeholders need to be periodically trained on the components and protocols for managing pregnant women living with HBV. The necessary logistics and management protocols need to be urgently provided. The skills and education obtained from the training will empower midwives to be knowledgeable about how to deliver quality care and provide education and support for HBV-infected pregnant women. The provision of logistics needed for the successful implementation of the program could avert delays associated with the administration of the hepatitis B birth dose vaccine and immunoglobulin to exposed newborns.

HBeAg testing is better than quantitative HBsAg assay as an alternative to HBV DNA assay among HBV-infected pregnant women.

Using tenofovir disoproxil fumarate (TDF) is recommended in the 3rd trimester for pregnant women with HBV DNA ≥ 200,000 IU/mL to prevent mother-to-child transmission (MTCT) of hepatitis B virus (HBV). However, HBV DNA quantification is unavailable in many resource-limited areas worldwide, hence prophylaxis is often missed. The aim of this study was to determine whether HBeAg or qHBsAg is a better alternative to HBV DNA testing in HBV-infected pregnant women. In this prospective cohort study, pregnant women with HBV infection were recruited in 3 hospitals from October 2019 to November 2020. Socio-demographic and clinical data were collected. Blood samples were taken for qHBsAg and HBV DNA testing. HBeAg results were collected from the medical records of the participants who visited a doctor during the study. 465 pregnant women met the study criteria. 41.9% were HBeAg positive, 33.3% had high qHBsAg levels (> 104 IU/mL), 38.3% had high HBV DNA levels (≥ 200,000 IU/mL). Pregnant women with high qHBsAg levels were 27 times more likely to have high HBV DNA levels (aOR = 27.0, 95% CI: 11.1-65.5, p < 0.001). Participants who were HBeAg positive were 57.5 times more likely to have high HBV DNA levels (aOR = 57.5, 95% CI: 23.0-140.0, p < 0.001). The sensitivity of qHBsAg and HBeAg was 80% and 94%, respectively; and specificity was 95% and 90%, respectively. HBeAg testing should be considered over qHBsAg assay as an alternative to HBV DNA assay because of its technical simplicity, lower cost, and fewer missed treatments.

Traditional medicine consumption in postpartum for HBV-infected women enrolled in the ANRS 12345 TA PROHM study in Cambodia.

In Cambodia, traditional medicine was commonly described as being used by pregnant women at two time points: one month before birth and during early postpartum. The present study aims to describe traditional medicine consumption during postpartum phase for women enrolled in the TA PROHM study and to investigate the possible association between traditional medicine consumption and acute liver toxicity. An ethnobotanical survey was conducted in 2 groups of HBV-infected pregnant women (with and without postpartum hepatocellular injury) enrolled in the study. Hepatocellular injury was defined by having Alanine Aminotransferase (ALT) > 2.5 times the Upper Limit of Normal (ULN = 40 U/L) at the 6th week postpartum visit. Interviews were done using a standardized questionnaire. Plant samples were collected and later identified by two traditional healers. Chi-square test was used to find the association between hepatocellular injury and traditional medicine consumption or a specific plant species. In total, 75 women were enrolled and 52 (69.3%) used at least one traditional remedy composed of 123 different plants and 12 alcoholic macerations of porcupine stomach. Orally consuming at least one remedy with alcohol was significantly associated with hepatocellular injury (33% vs 13%, p = 0.034). Among the 123 plants species identified, four were found to be associated with hepatocellular injury, namely Amphineurion marginatum (Roxb.) D.J.Middleton [Apocynaceae] (p = 0.022), Selaginella tamariscina (P.Beauv.) Spring [Selaginellaceae] (p = 0.048), Mitragyna speciosa Korth. [Rubiaceae] (p = 0.099) and Tetracera indica (Christm. & Panz.) Merr. [Dilleniaceae] (p = 0.079). Consumption of traditional medicine in postpartum is a common practice for women enrolled in the TA PROHM study. Alcohol-based remedies may exacerbate the risk of acute hepatocellular injury in HBV-infected women already exposed to immune restoration. The complex mixtures of herbs need to be further evaluated by in vitro and in vivo studies.

Frequency of drug resistance and immune escape mutations in the hepatitis B virus genome detected in pregnant women in the Republic of Guinea

The aim of the work is to assess the prevalence of hepatitis B virus drug resistance mutations and immune escape mutations in pregnant women in the Republic of Guinea.&#x0D; Materials and methods. Blood plasma samples obtained from 480 pregnant women from different regions of the Republic of Guinea with laboratory-confirmed viral hepatitis B were studied. Nucleotide sequences for genotype identification and mutation detection were obtained using nested-PCR followed by Sanger sequencing, based on overlapping pairs of primers spanning the complete genome of the virus.&#x0D; Results and discussion. In the examined group, the viral genotype E was the most prevalent (92.92%) compared with subgenotypes A1 (1.67%), A3 (1.46%), D1 (0.63%), D2 (1.04%) and D3 (2.29%). Among the examined HBV-infected pregnant women, 188 (39.17%) had undetectable HBsAg. Drug resistance mutations were detected in 33 individuals, which amounted to 6.88%. The following mutations were found: S78T (27.27%), L80I (24.24%), S202I (15.15%), M204I/V (42.42%). The presence of polymorphic variants not described as drug resistant has also been shown in positions associated with the development of drug resistance to tenofovir, lamivudine, telbivudine and entecavir (L80F, S202I, M204R). When analyzing the MHR and the region of a determinant, mutations were detected in 318 (66.25%) of pregnant women. In 172 of them, which amounted to 54.09%, multiple mutations were found. The amino acid substitutions in 13 positions associated with HBsAg-negative hepatitis B and/or potentially affecting HBsAg antigenicity were identified.&#x0D; Conclusion. The high prevalence of immune escape and drug resistance mutations potentially associated with false-negative result of HBsAg screening, prophylaxis failure, and virological failure of therapy that has been identified among treatment naive pregnant women imposes a serious problem.

Informing a target product profile for rapid tests to identify HBV-infected pregnant women with high viral loads: a discrete choice experiment with African healthcare workers

BackgroundElimination of mother-to-child transmission of hepatitis B virus (HBV) requires infant immunoprophylaxis and antiviral prophylaxis for pregnant women with high viral loads. Since real-time polymerase chain reaction (RT-PCR), a gold standard for assessing antiviral eligibility, is neither accessible nor affordable for women living in low-income and middle-income countries (LMICs), rapid diagnostic tests (RDTs) detecting alternative HBV markers may be needed. To inform future development of the target product profile (TPP) for RDTs to identify highly viremic women, we used a discrete choice experiment (DCE) and elicited preference and trade-off of healthcare workers (HCW) in Africa between the following four attributes of fictional RDTs: price, time-to-result, diagnostic sensitivity, and specificity.MethodsThrough an online questionnaire survey, we asked participants to indicate their preferred test from a set of two RDTs in seven choice tasks with varying levels of the four attributes. We used mixed multinomial logit models to quantify the utility gain or loss generated by each attribute. We attempted to define minimal and optimal criteria for test attributes that can satisfy ≥ 70% and ≥ 90% of HCWs, respectively, as an alternative to RT-PCR.ResultsA total of 555 HCWs from 41 African countries participated. Increases in sensitivity and specificity generated significant utility and increases in cost and time-to-result generated significant disutility. The size of the coefficients for the highest attribute levels relative to the reference levels were in the following order: sensitivity (β = 3.749), cost (β = -2.550), specificity (β = 1.134), and time-to-result (β = -0.284). Doctors cared most about test sensitivity, while public health practitioners cared about cost and midwives about time-to-result. For an RDT with 95% specificity, costing 1 US$, and yielding results in 20 min, the minimally acceptable test sensitivity would be 82.5% and the optimally acceptable sensitivity would be 87.5%.ConclusionsAfrican HCWs would prefer an RDT with the following order of priority: higher sensitivity, lower cost, higher specificity, and shorter time-to-result. The development and optimization of RDTs that can meet the criteria are urgently needed to scale up the prevention of HBV mother-to-child transmission in LMICs.

Tenofovir alters the immune microenvironment of pregnant women with hepatitis B virus infection: Evidence from single-cell RNA sequencing.

Mother-to-child is the main route of the transmission of hepatitis B virus (HBV) infection. Tenofovir fumarate (TDF) antiviral treatment has become the most extensive choice worldwide. However, the effects of TDF treatment on the immune function of pregnant women remains unclear. Here we investigate the effect of TDF treatment on the immune microenvironment of pregnant women with HBV infection using single-cell RNA sequencing (scRNA-seq). Three HBV-infected pregnant women were treated with TDF and six samples were collected before and after the treatment. In total, 68,200 peripheral blood mononuclear cells (PBMCs) were extracted for 10×scRNA-seq. The cells were clustered using t-distributed stochastic neighbor embedding (t-SNE) and unbiased computational informatics analysis. The analysis identified four-cell subtypes, including T cells, monocytes, natural killer (NK) cells, and B cells, and unraveled the developmental trajectory and maturation of CD4+ T and CD8+ T cell subtypes. The cellular state and molecular features of the effector/memory T cells revealed a significant increase in the inflammatory state of CD4+ T cells and the cytotoxic characteristics of CD8+ T cells. Additionally, after TDF treatment, the monocytes showed a tendency for M1 polarization, and the cytotoxicity of NK cells was enhanced. Furthermore, the analysis of intercellular communication revealed the interaction of various subtypes of cells and the heterogeneous expression of key signal pathways. The findings of this study reveal significant differences in cellular subtypes and molecular characteristics of PBMCs of pregnant women with HBV infection before and after TDF treatment and demonstrate the recovery of immune response after treatment. These findings could help develop immune intervention measures to control HBV during pregnancy and the puerperium period.

FRI-191 - What is the most effective strategy to identify HBV-infected pregnant women eligible for antiviral prophylaxis in Burkina Faso? A modelling study on different testing strategies

FRI-191 - What is the most effective strategy to identify HBV-infected pregnant women eligible for antiviral prophylaxis in Burkina Faso? A modelling study on different testing strategies

Single-cell RNA sequencing reveals transcriptional profiles of monocytes in HBV-infected pregnant women during mid-pregnancy.

There is a growing body of evidence that innate immunity also plays an important role in the progression of hepatitis B virus (HBV) infection. However, there is less study on systematically elucidating the characteristics of innate immunity in HBV-infected pregnant women. We compared the features of peripheral blood mononuclear cells in three healthy pregnant women and three HBV-infected pregnant women by single-cell RNA sequencing. 10 DEGs were detected between groups and monocytes were the main expression source of most of the DEGs, which involved in the inflammatory response, apoptosis and immune regulation. Meanwhile, qPCR and ELISA were performed to verify above genes. Monocytes displayed immune response defect, reflecting poor ability of response to IFN. In addition, eight clusters were identified in monocytes. We identified molecular drivers in monocytes subpopulations.TNFSF10+ monocytes, MT1G+ monocytes and TUBB1+ monocytes were featured with different gene expression pattern and biological function.TNFSF10+ monocytes and MT1G+ monocytes were characterized by high levels of inflammation response.TNFSF10+ monocytes, MT1G+ monocytes and TUBB1+ monocytes showed decreased response to IFN. Our results dissects alterations in monocytes related to the immune response of HBV-infected pregnant women and provides a rich resource for fully understanding immunopathogenesis and developing effective preventing HBV intrauterine infection strategies.

Hepatitis B core-related antigen serum levels may be a predictor of acute flare of chronic hepatitis B among pregnant women in the immune-tolerant phase of chronic HBV infection after short-course antiviral therapy

ABSTRACT Background Studies have shown acute flares of chronic hepatitis B (CHB) might be related to immunologic changes that occur during pregnancy. However, the indicators for predicting acute flares of CHB among pregnant women still need further study. We aimed to distinguish the relevance between serum levels of HBcrAg and acute flares of CHB in pregnant women in the immune-tolerant phase of chronic HBV infection after short-course antiviral therapy. Methods A total of 172 chronic HBV-infected pregnant women who were judged to be in the immune-tolerant phase were recruited in our research. All patients received short-course antiviral therapy with TDF. The biochemical, serological, and virological parameters were measured using standard laboratory procedures. The serum levels of HBcrAg were tested by ELISA. Results Fifty-two (30.2%) out of 172 patients had acute flares of CHB. At postpartum week 12 (TDF cessation), serum HBcrAg (OR, 4.52; 95% CI, 2.58–7.92) and HBsAg (OR, 2.52; 95% CI, 1.13–5.65) were associated with acute flares of CHB. The serum HBcrAg levels were beneficial for confirmation of patients with acute flares of CHB, with an area under the ROC curve of 0.84 (95% CI, 0.78–0.91). Conclusions For pregnant women with chronic HBV infection in the immune-tolerant phase, serum HBcrAg and HBsAg levels at postpartum week 12 were associated with acute flares of CHB after short-course antiviral therapy with TDF. The serum HBcrAg level can correctly identify acute flares of CHB and may be a predictor of the need for continuing antiviral therapy after 12 weeks postpartum.

A retrospective study of hepatitis B vaccination in preterm birth and low birth weight infants born to hepatitis B surface antigen-positive mothers: Time to close the policy-practice gap

ABSTRACT National Immunization Program-version 2016 (ISIV-NIP-v2016) recommended a 4-dose hepatitis B vaccine (HepB) schedule for preterm birth (PTB) and low birth weight (LBW) infants born to HBsAg-positive mothers. However, the implementation of this immunization strategy in the past five years has not been fully evaluated in China. We reviewed the data of pregnant women and live-born infants from 24 hospitals between 2016 and 2021 in Lu’an, Anhui province, to estimate the prevalence of PTB, LBW, and hepatitis B virus (HBV) infected pregnant women. We analyzed the vaccination status of HepB and HBIG among PTB and LBW infants born to HBsAg-positive mothers. A total of 160 222 pregnant women and 159 613 live-born infants were included in this study. The estimated prevalence of PTB, LBW and HBV-infected pregnant women was 3.86% (range: 3.28%-5.10%), 2.77% (range: 2.12%-3.66%), and 3.27% (range: 3.03%-3.49%), respectively. We screened 340 PTB and LBW infants born to HBsAg-positive mothers between 2016 and 2020. We found that the coverage of HepB and HBIG among them was 100% and 99.39%. However, the timely vaccination rate of the HepB birth dose was only 78.59% and only four children (1.22%) received the 4-dose HepB as recommended by ISIV-NIP-v2016. The 4-dose of HepB for PTB and LBW infants born to HBsAg-positive mothers recommended by ISIV-NIP-v2016 was not fully implemented. A strong public health intervention should be taken to close the policy-practice gap in China in the future.

Impaired CD8+ T cells in term pregnancy decidua with chronic hepatitis B virus infection.

Hepatitis B virus (HBV) infection is more likely to develop a state of chronicity in early life, particularly mother-to-child transmission (MTCT) of HBV in the fetus during pregnancy. Till now, little is known about the impact of chronic HBV infection on the immune status of the maternal-fetus interface, and the immune profile of placental lymphocytes in MTCT of HBV is poorly understood. Thirteen term pregnant women with chronic HBV infection (HBV-PW) and thirteen normal pregnant women as healthy control (HC-PW) were enrolled. The profile of placental immune cells and paired peripheral blood were analyzed by flow cytometry and immunohistochemistry. Compared with HC-PW, the frequency of CD8+ T cells from the term placenta of HBV-PW was significantly reduced. These cells showed decreased expression of activation molecules CD69 and HLA-DR; thus, decidual CD8+ T cells from HBV-PW demonstrated hypofunctional signature as evidenced by significantly reduced production of IFN-γ, as well as compromised ability of degranulation and proliferation. These findings supported that hypoactivated decidual CD8+ T cells might possess compromised ability in chronically HBV-infected term pregnant women. Our study provides robust evidence for the necessity and importance of antiviral intervention in HBV-PW to prevent MTCT of HBV.

Hepatitis B Virus Infection and Increased Risk of Gestational Diabetes Regardless of Liver Function Status: A Xiamen Area Population-Based Study.

Background & Aims: Hepatitis B virus (HBV) infection is a significant cause of liver function damage. However, previous studies on HBV mainly aimed at ordinary people, and there is a lack of consensus on the relationship between HBV infection and gestational diabetes mellitus (GDM) and whether HBV-infected pregnant women should undergo antiviral treatment. In addition, systematic studies on the impact of HBV infection on GDM have rarely been studied directly. Therefore, the overall goal of this study was to pursue the association between HBV infection, liver function, and GDM using Xiamen area gestational big data. Methods: Using the Xiamen Primary Health Information System-maternal and child health information system, the data on participants (138,867 in total) expected confinement between 2008 and 2018 were included. Using univariate and multivariate logistic regressions, we constructed models to determine the role of HBV infection and liver function status in GDM. In addition, an analysis of variance tests was performed to study whether the relationship between HBsAg and GDM differed in the normal liver function and the abnormal liver function subgroups. Results: HBsAg's positive status showed a substantial correlation with GDM onset in univariate and multivariate logistic regressions (p < 0.001). Subgroup analysis among HBsAg, liver function, and GDM suggests that both HBsAg and liver function affect the onset of GDM and have the highest prevalence of both abnormalities. Furthermore, ANOVA was used to investigate the association of HBsAg positive (p < 0.001), abnormal liver function (p < 0.001), and their interaction (p = 0.302) on the onset of GDM. This result showed that HBsAg is an independent factor of GDM pathogenesis, regardless of liver function status. Conclusion: HBsAg and liver function are independent factors in GDM. Therefore, regarding these results, while clinicians consider the traditional risk factors of GDM, it is necessary to consider the HBV infection status. Conducting a dietary intervention for HBsAg-positive pregnant women at the early stage of pregnancy is conducive to reducing the adverse effects.