BackgroundThe main transmission route of the hepatitis B virus (HBV) is mother to child transmission and contributes significantly to chronic HBV infection. Even though immunoprophylaxis with hepatitis B immunoglobulin (HBIG) and hepatitis B vaccine is administrated to neonates whose mothers are hepatitis B surface antigen (HBsAg) positive, about 10% of the neonates suffer from HBV infection in their early life.ObjectivesTo survey chronic HBV infection among pregnant women and their infants and analyze the reason for immunoprophylaxis failure.MethodsSerum HBsAg was tested in all pregnant women. HBVDNA and other serum HBV markers including hepatitis B e antigen (HBeAg), hepatitis B core antibody (anti-HBc) and hepatitis B surface antibody (anti-HBs) were tested among HBsAg positive pregnant women. All infants whose mothers were HBsAg positive were vaccinated with a standard immunoprophylaxis. Serum HBV markers and HBVDNA were tested among these infants at 7 months of age. HBV genotypes were analyzed among the infants and pregnant women who were HBVDNA positive.ResultsThe prevalence of HBsAg, anti-HBc and anti-HBs among 4,536 pregnant women was 5.49%, 29.65% and 58.55%, respectively. The prevalence of HBsAg, anti-HBc and anti-HBs among pregnant women older than 20 years of age was significantly different compared to pregnant women younger than 20 years of age (4.54, 5.69 and 0.61 times, prevalence older vs. younger, respectively. P<0.05, 0.01, 0.05, respectively). Among 249 HBsAg positive pregnant women, 167 (67.07%) were HBeAg positive, 204 (81.93%) were HBVDNA positive and only 37 (14.86%) had HBVDNA >107 IU/ml. Among the infants whose mothers were HBsAg positive, 214 (85.94%) infants were anti-HBs positive. There were 12 (4.82%) infants who were HBsAg and HBVDNA positive, and all 12 of these infants mothers were HBeAg positive and had HBVDNA >107 IU/ml. Genotypes B and C were present among 165 pregnant women and genotype C was present in 85 pregnant women. There were 12 infants who were HBsAg positive and had the same HBV genotypes as their mothers. There was a significant difference in genotypes between the pregnant women whose infants were infected with HBV compared to those without HBV infection (P < 0.05).ConclusionsThere was a significant decline in HBsAg prevalence among pregnant women and their infants in Shenyang. Genotype C might be a risk factor for mother to child transmission of HBV.

Summary Background Data on tenofovir alafenamide fumarate (TAF) for preventing mother‐to‐child transmission of hepatitis B virus (HBV) are lacking. Aims To investigate the efficacy and safety of TAF therapy for preventing hepatitis B mother‐to‐child transmission. Methods Mothers with chronic HBV infection, positive for hepatitis B e‐antigen and with HBV DNA >200 000 IU/mL received TAF for preventing mother‐to‐child transmission were enrolled retrospectively from multiple centres with data collection on mother‐infant dyads up to postpartum week 24‐28. Primary measurements were the mother‐to‐child transmission rate and infants' malformation rate. Secondary assessments included maternal HBV DNA reduction at delivery, and maternal or infant adverse events during follow up. Results Among 71 mothers enrolled, the mean (±SD) age was 30.3 (±2.2) years. TAF was initiated during the second or third trimester and continued to delivery with a mean (±SD) duration of 12.8 (±4.0) weeks. At delivery, 85.9% (61/71) of the mothers achieved HBV DNA <200 000 IU/L. Seventy‐three infants (two sets of twins) were born from mothers treated with TAF and none had congenital defects or malformations. All infants received HBV immunoglobulin and vaccine at birth with additional HBV vaccinations at one and six months. At age 24‐28 weeks, all infants had negative hepatitis B surface antigen and undetectable levels of HBV DNA (<100 IU/mL). Body weight, height, and head circumferences were comparable to national standards for physical development. No severe adverse effects were reported in either mothers or infants. Conclusions TAF for highly viraemic mothers effectively prevented mother‐to‐child transmission of hepatitis B. There were no safety concerns for either mothers or infants with 24‐28 weeks of follow up.

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Preventing hepatitis B virus (HBV) mother-to-child transmission (MTCT) is the key to controlling the prevalence of chronic HBV infection. Adequate awareness of hepatitis B in hepatitis B s antigen (HBsAg) positive pregnant women may be helpful to reduce HBV MTCT.The aim of this study was to explore HBV seroprevalence among pregnant women and investigate the level of hepatitis B awareness among HBsAg positive pregnant women.HBV serum biomarkers were tested among pregnant women visiting Shengjing Hospital of China Medical University. HBsAg-positive pregnant women received a HBV DNA test and completed a questionnaire. The different HBV DNA loads were interpreted as follows: 20 to < 2 × 10 IU/mL was low viral load, 2 × 10 to < 2 × 10 IU/mL was intermediate viral load and ≥2 × 10 IU/mL was high viral load. The pregnant women with high viral load were treated with telbivudine (LdT). HBV DNA at different times was tested. The rate of HBV MTCT was confirmed at 28 weeks postpartum.HBsAg prevalence among pregnant women was 3.1% (441/14314). There was significant difference in comparing HBsAg prevalence in different age groups (χ = 13.86, P < .01). Among 441 HBsAg-positive pregnant women, 151 (34.2%) were hepatitis B e antigen (HBeAg) positive and 112 (25.4%) had high viral load. After 4 weeks of treatment, the average HBV DNA load of 66 cases with high viral load was (5.0 ± 0.8) log10 IU/mL. The average HBV DNA load at 4 weeks postpartum rebounded to (7.9 ± 1.0) log10 IU/mL, which was not significantly different from that at baseline (t = 1.23, P = .22). At 28 weeks postpartum, the rate of HBV MTCT in the treatment group was significantly lower than that in the observation group (0% vs 12.2%; P = .02). Only 23.4% of pregnant women knew their HBV status before gestation and 17.7% of pregnant women knew the HBV status before delivery. However, only 21.3% of pregnant women realized to need antiviral treatment to prevent MTCT.The pregnant women in Shenyang had a low HBsAg prevalence. Antiviral treatment for pregnant women with high viral load can effectively reduce the rate of HBV MTCT. HBV screening and education among HBsAg-positive pregnant women should be strengthened.

Nucleos(t)ide analogues (NAs) have been widely used for the treatment of chronic hepatitis B (CHB). Because viral DNA polymerase lacks proofreading function (3′ exonuclease activity), theoretically, the incorporated NAs would irreversibly terminate viral DNA synthesis. This study explored the natures of nascent hepatitis B virus (HBV) DNA and infectivity of progeny virions produced under NA treatment. HBV infectivity was determined by infection of HepG2‐NTCP cells and primary human hepatocytes (PHHs). Biochemical properties of HBV DNA in the progeny virions were investigated by qPCR, northern blotting, or Southern blotting hybridization, sucrose gradient centrifugation, and in vitro endogenous DNA polymerase assay. Progeny HBV virions produced under NA treatment were mainly not infectious to HepG2‐NTCP cells or PHHs. Biochemical analysis revealed that under NA treatment, HBV DNA in nucleaocapsids or virions were predominantly short minus‐strand DNA with irreversible termination. This finding was supported by the observation of first disappearance of relaxed circular DNA and then the proportional decline of HBV‐DNA levels corresponding to the regions of PreC/C, S, and X genes in serial sera of patients receiving NA treatment. Conclusion: HBV virions produced under NA treatment are predominantly replication deficient because the viral genomes are truncated and elongation of DNA chains is irreversibly terminated. Clinically, our results suggest that the viral loads of CHB patients under NA therapy vary with the different regions of genome being detected by qPCR assays. Our findings also imply that NA prevention of perinatal and sexual HBV transmission as well as infection of transplanted livers works not only by reducing viral loads, but also by producing noninfectious virions.

We previously identified that miR-130a downregulates HCV replication through two independent pathways: restoration of host immune responses and regulation of pyruvate metabolism. In this study, we further sought to explore host antiviral target genes regulated by miR-130a. We performed a RT² Profiler™ PCR array to identify the host antiviral genes regulated by miR-130a. The putative binding sites between miR-130a and its downregulated genes were predicted by miRanda. miR-130a and predicted target genes were over-expressed or knocked down by siRNA or CRISPR/Cas9 gRNA. Selected gene mRNAs and their proteins, together with HCV replication in JFH1 HCV-infected Huh7.5.1 cells were monitored by qRT-PCR and Western blot. We identified 32 genes that were significantly differentially expressed more than 1.5-fold following miR-130a overexpression, 28 of which were upregulated and 4 downregulated. We found that ATG5, a target gene for miR-130a, significantly upregulated HCV replication and downregulated interferon stimulated gene expression. miR-130a downregulated ATG5 expression and its conjugation complex with ATG12. ATG5 and ATG5-ATG12 complex affected interferon stimulated gene (ISG) such as MX1 and OAS3 expression and subsequently HCV replication. We concluded that miR-130a regulates host antiviral response and HCV replication through targeting ATG5 via the ATG5-dependent autophagy pathway.

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