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The new research of intrauterine transmission of HBV includes intrauterine dominant infection and occult infection. Intrauterine dominant infection of HBV is the traditional intrauterine infection. Although intrauterine infection of HBV has been studied for decades, the intervention effects on HBV infection are very limited. As a result, mother to child transmission has become the main route of the transmission of HBV. With the development of science and technology, people’s understand of intrauterine occult infection of HBV has been deepened, and the definition of intrauterine transmission of HBV has been further completed and expanded. The study of intrauterine occult infection of HBV will play an important role in prevention and control of hepatitis B in China through filling in a gap in the field of prevention and control of vertical transmission of HBV, exploring new research perspective and providing guideline for related decision-making.
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Objective@#To investigate the current status and influence factors of HBV intrauterine transmission (BIT) in HBsAg-positive parturients and understand the outcome of HBV transmission and response to hepatitis B vaccine immunization in children in Xi’an.@*Methods@#An epidemiological survey was conducted in 341 HBsAg-positive parturients who gave birth in Northwest Women and Children Hospital of Shaanxi Province from January 2015 to January 2018. Serological tests were performed by using venous blood from 344 newborns within 24 hours after birth and at the age of 1 year old. A nested case-control study was conducted to analyze the infection rates of intrauterine dominate HBV infection (DBI) and intrauterine occult HBV infection (OBI) in BIT and their influencing factors in newborns. The epidemiological survey was conducted to collect the information about the outcome of HBV transmission and the positive rate of HBsAb in children at high-risk from August 2016 to October 2018.@*Results@#The BIT rate was 46.51%(160/344) in HBsAg-positive parturients, the DBI rate was 8.14% (28/344), the OBI rate was 38.37% (132/344), and the odds ratio of DBI and BIT in neonates of HBeAg-positive parturients were respectively 2.60 (95%CI: 1.19-5.70) and 2.21 (95%CI: 1.36-3.61) times higher than that of HBeAg-negative parturients. The odds ratio of BIT in neonates with maternal peripheral blood HBV DNA load ≥200, ≥103 and>106 copies/ml were 1.99 (95%CI: 1.29-3.08), 1.73 (95%CI: 1.11-2.69) and 2.33 (95%CI: 1.33-4.10) times higher than those in neonates with maternal peripheral blood HBV DNA<200,<103, and ≤106 copies/ml respectively. The incidence of DBI in neonates of parturients with placenta previa was 14.07 times higher than that of parturients without placenta previa (95%CI: 1.23-160.76). The incidence of BIT in neonates of parturients who received no hepatitis B immunoglobulin during pregnancy was 1.60 times higher than that in neonates of those who received hepatitis B immunoglobulin (95%CI: 1.02-2.53). Follow-up results showed that HBsAg negative conversion was found in 9 of 14 children with DBI, and 24.17%(22/91) of children had OBI. The overall rate of immune response to hepatitis B vaccine was 69.23%(63/91). The immune response rate in children with OBI was only 59.09%(13/22).@*Conclusion@#Newborns of HBsAg-positive parturients had high rate of OBI and lower rate of immune response to hepatitis B vaccine detected in follow-up, indicating a gap in hepatitis B prevention and control. HBV monitoring and intervention in HBsAg-positive women of childbearing age and hepatitis B antibody monitoring in children at high-risk are important measures to control infection source and protect susceptible population.
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Objective@#To explore the role of TLR 9 in intrauterine transmission of hepatitis B virus (HBV) through blood pathway and placenta.@*Methods@#Epidemiological investigation was carried out in 290 HBsAg positive parturients and 45 normal parturients (control group) in Northwest Women and Children Hospital of Shaanxi Province. Enzyme-linked immunosorbent assay (ELISA) was used to detect five serological makers of hepatitis B and TLR 9 levels in peripheral blood of pregnant women and newborns. HBV DNA was detected by real-time fluorescence quantitative PCR. Detection of TLR 9 expression in placenta by immunohistochemical method. A case-control study was conducted to analyze the difference of TLR 9 levels in placenta and peripheral blood of HBsAg- positive pregnant women with intrauterine transmission of HBV.@*Results@#The incidence of dominant HBV infection (DBI), occult HBV infection (OBI) and intrauterine transmission of HBV were 9.28% (27/291), 40.21% (117/291) and 49.48% (144/291) respectively. (1) The level of TLR 9 in peripheral blood of HBsAg-positive parturients, non-HBV intrauterine transmission (NBIT) group and OBI group were significantly lower than that of control group (P<0.001). The level of TLR 9 in DBI group was significantly higher than those in NBIT group and OBI group (P=0.000). (2) The TLR 9 level in HBeAg-negative group was significantly lower than that in HBeAg-positive parturients in OBI group (P=0.01). (3) With the increased severity of intrauterine transmission of HBV in each HBV DNA load group, the TLR 9 level in maternal peripheral blood increased significantly (P<0.05). (4) With the increased severity of intrauterine transmission of HBV, the levels of TLR 9 increased significantly in antiviral therapy, immunoglobulin injection and non-hepatitis B vaccine groups (P<0.05). (5) The expression of TLR 9 in placenta tissues with DBI group was significantly higher than that in OBI group and NBIT group (P<0.05).@*Conclusions@#HBV can inhibit the secretion of TLR 9 in parturient to some extent, but HBeAg can stimulate the secretion of TLR 9. However, with the increased severity of intrauterine transmission of HBV, the level of TLR 9 in parturients is increased by intra-group cross-differentiation. Therefore, TLR 9 is not an independent marker for screening and grouping, but it can be used as an reference indicator for the monitoring and management of HBsAg-positive parturients.
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Objective@#To investigate the expression of IL-18 in peripheral blood of HBsAg positive parturients in intrauterine transmission of HBV.@*Methods@#A case-control study was conducted in 282 HBsAg positive parturients and 43 health parturients (control group) in Northwest Women and Children Hospital of Shaanxi Province. Enzyme-linked immunosorbent assay (ELISA) was used to detect five serological makers of hepatitis B, real time PCR was used to detect HBV DNA, and flow liquid chip method was used to detect IL-18 levels in peripheral blood of parturients and newborns.@*Results@#The incidence of dominant HBV infection (DBI), occult HBV infection (OBI) and intrauterine transmission of HBV were 8.42% (24/285), 40.00% (114/285) and 48.42% (138/285), respectively. The level of IL-18 in peripheral blood of HBsAg-negative parturients were significantly lower than those of HBsAg-positive parturients (P=0.001), non-HBV intrauterine transmission (NBIT) group (P=0.001) and OBI group (P<0.001). The level of IL-18 in HBeAg negative group was significantly lower than that in HBeAg positive group (P=0.023). When HBV DNA load was ≥103 copies/ml, the level of IL-18 was significantly higher than that in HBsAg-negative group (P<0.01). With the increase of HBV DNA load in maternal blood, the level of IL-18 increased (P=0.024). When HBV DNA load was 103-106 copies/ml, the level of IL-18 in DBI group was significantly lower than that in NBIT group (P=0.022), and increased with the increase of HBV DNA load in maternal blood (P=0.016). With the increased severity of intrauterine transmission of HBV, the level of IL-18 in non-hepatitis B vaccine group decreased significantly (P=0.044). The level of IL-18 in non-hepatitis B vaccine group and immunoglobulin injection group was significantly higher than that in NBIT group (P<0.05). Multivariate analysis showed that the linear relationship between maternal HBeAg status and maternal IL-18 levels had statistical significance (P=0.01).@*Conclusions@#IL-18 is a higher level balance regulator of Th1/Th2 immune network. Monitoring the level of IL-18 in HBsAg-positive parturients can be used not only for predicting the probability of DBI and OBI, but also as an intervention mean, especially for those who are HBeAg-positive and had HBV DNA load ≥103 copies/ml, to improve maternal cellular immune function, which is conducive to interrupting intrauterine transmission and providing a theoretical basis for the prevention and control of HBV intrauterine transmission.
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Objective@#To investigate the influence of IFN-γ and IL-12 levels in prenatal peripheral blood of HBsAg-positive parturients on intrauterine transmission of hepatitis B virus (HBV).@*Methods@#A case-control study was conducted in 282 HBsAg positive parturients and 43 health parturients (control group) in Northwest Women and Children Hospital of Shaanxi Province. Enzyme-linked immunosorbent assay (ELISA) was used to detect five serological makers of hepatitis B in peripheral blood of parturients. HBV DNA was detected by real-time fluorescence quantitative PCR. Detection of cytokines IFN-γ and IL-12 levels were conducted with liquid chip-based flow cytometry method. The serum levels of five serological markers of hepatitis B and HBV DNA in 285 newborns were detected within 24 hours after birth.@*Results@#The incidence of intrauterine dominant infection (DBI), occult infection (OBI) and intrauterine transmission of HBV in HBsAg positive parturients were 7.37% (21/285), 40.70% (116/285) and 48.07% (137/285), respectively. The level of IFN-γ in peripheral blood of HBsAg-negative parturients was significantly lower than those of HBsAg-positive parturients (t=-2.55, P=0.011), NBIT group (t=-2.54, P=0.012) and OBI group (t=-2.33, P=0.021). In HBV DNA load of 103-106 copies/ml group, the levels of IFN-γ in the DBI group were significantly lower than those in OBI group and NBIT group (P<0.01). The level of IFN-γ in maternal peripheral blood decreased significantly with the increased severity of intrauterine transmission of HBV (χ2=6.40, P=0.041). In the antiviral treatment group, the level of IL-12 in maternal peripheral blood decreased significantly with the increased severity of intrauterine transmission of HBV (χ2=8.90, P=0.012). Multivariate analysis showed that there was a significant linear relationship between maternal IFN-γ level and maternal age, placenta previa and hepatitis B vaccine injection (P<0.05). The linear relationship between the level of maternal IL-12 and the mode of rupture and hepatitis B vaccine injection had statistical significance (P<0.05).@*Conclusions@#HBV can stimulate the expression of IFN-γ and inhibit the secretion of IL-12 in pregnant and lying-in women, but the expression of IFN-γ in HBsAg-positive parturients showed intra-group differentiation, and the maternal level of IFN-γ will decrease in HBeAg-positive and high-HBV DNA loadstatus. Increasing the levels of IFN-γ and IL-12 in HBsAg-positive parturients is beneficial to block intrauterine transmission of HBV, especially DBI.