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Objective: To explore the relationship between the status of HBsAg-positive infection of mothers and the non/low-response to hepatitis B vaccine of their infants. Methods: A total of 225 pairs of mothers and their infants were recruited in our cohort from June 2011 to July 2013. Infants were given three doses of hepatitis B vaccine at hour 24, first month and month 6(t)h respectively and were followed up for one year after birth. HBV serological markers and HBV DNA in the peripheral blood of both mothers and infants were detected by Electro-chemiluminescence immunoassay and fluorescence quantitative Polymerase Chain Reaction. Results: Six HBV infection models were detected in HBsAg-positive mothers, and "HBsAg (+), HBeAg (+), anti-HBc (+)" (model one) and "HBsAg (+), anti-HBe (+), anti-HBc (+)" (model two) accounted for 92.5 % (208/225) of all the models. Rate of non/low-response to hepatitis B vaccine in infants born to mothers in model one was lower than those in model two, the differences are statistically significant ( χ (2)=4.80, P =0.029). The rate of non/low-response to hepatitis B vaccine in infants showed a downward trend with the rising of HBeAg level in their mothers ( χ (2)=4.86, P =0.028). Results from the unconditional logistic regression analysis showed that the HBeAg of the HBsAg-positive mothers was significantly correlated with the low risk of non/low-response to hepatitis B vaccine in infants ( OR =0.598, 95 %CI : 0.378-0.947). The positive rate of serum HBV DNA in HBsAg-positive mothers was 54.2 % , while the rate of non/low-response to hepatitis B vaccine in infants born to HBV DNA positive mothers was similar to those infants born to HBV DNA negative mothers ( χ (2)=0.22, P =0.640). Conclusions: "HBsAg (+), HBeAg (+), anti-HBc (+)" and "HBsAg (+), anti-HBe(+), anti-HBc (+)" were the common models seen in HBsAg-positive mothers, and the rate of non/low-response to hepatitis B vaccine was different between the two models. HBeAg of HBsAg-positive mothers might have positive effects on the immune response to hepatitis B vaccine in infants but the mechanisms remained not clear. HBV DNA of the HBsAg-positive mothers did not seem to be correlated with the immune response to hepatitis B vaccine in infants.

Objective: To investigate the influencing factors for non/low-response to hepatitis B vaccine in infants of HBsAg-positive mothers. Methods: A total of 286 HBsAg-positive pregnant women and their infants were recruited from the Third People's Hospital of Taiyuan during July 2011 to January 2013. The infants were immunized with hepatitis B vaccine according to the 0-1-6 month vaccination schedule and followed up for 12 months. The serum HBV DNA level of mothers, neonates and infants were detected by electro chemilum inescence immunoassay kits and fluorescene quantiative polymerase chain rection. Results: Among 286 infants, the rate of non/low-response to hepatitis B vaccine was 18.53 % (53/286). Non-conditional logistic regression analysis indicated that the mother's HBV DNA level ≥1×10(7) copies/ml ( OR =2.592, 95 %CI : 1.121-5.996) and natural birth ( OR =1.932, 95 %CI : 1.021-3.654) were the risk factors for non/low-response to hepatitis B vaccine, the risks were 2.592 times and 1.932 times higher compared with the infants whose mothers were HBV DNA negative and the infants whose mothers had cesarean delivery. There was no multiplicative or additive interaction between high HBV DNA load and natural birth ( OR =1.055, 95 %CI : 0.209-5.321), ( RERI =1.617, 95 %CI : -4.038-7.272; AP =0.364, 95 %CI : -0.527-1.225; SI =1.195, 95 %CI : 0.270-13.135). After stratified analysis of mother's HBV DNA level, delivery mode of mothers was not associated with non/low-response of their infants. Conclusion: The mother's load of HBV DNA≥1×10(7) copies/ml might be the factor for non/low-response to hepatitis B vaccine in infants of HBsAg positive mothers.

Objective: To explore the effect of interleukin-6 (IL-6) and Interleukin-12 (IL-12) on immune response to hepatitis B vaccination in infants of HBsAg-positive mothers. Methods: A total of 91 neonates whose mothers were HBsAg-positive were included and followed up for 12 months. HBV DNA and HBV serological markers in the peripheral blood of the neonates and infants were detected with fluorescence quantitative polymerase chain reaction (FQ-PCR) and chemiluminescence immunoassay (CLIA), and the levels of IL-6 and IL-12 in the peripheral blood of the neonates and infants were detected with enzyme-linked immunosorbent assay (ELISA). Results: The non-/hypo-response rate to hepatitis B vaccination was 35.16 % (32/91) in the 91 infants. In the neonatal period and infantile period, the level of IL-6 in non-/hypo-response group was lower than that in high-response group, while the level of IL-12 was higher than that in high-response group, and there was significant difference ( P <0.01). From the neonatal period to the infantile period, the level of IL-6 increased, while the level of IL-12 descended in both groups, and there was significant difference ( P <0.01). Furthermore, the level of anti-HBs of infants was positively correlated with the level of IL-6 ( r(s) =0.70, 0.79, P <0.01), and was negatively correlated with the level of IL-12 ( r(s) =-0.71, -0.72, P <0.01) in the neonatal period and the infantile period. From the neonatal period to the infantile period, the increased level of IL-6 was positively associated with the level of anti-HBs ( r(s) = -0.74, P <0.01), while the decreased level of IL-12 was negatively associated with the level of anti-HBs ( r(s) =-0.42, P <0.01). The level of IL-6 was negatively correlated with the level of IL-12 in the neonatal period and the infantile period ( r(s) =-0.68, -0.70, P <0.01). Conclusions: IL-6 might promote the immune response to hepatitis B vaccination in infants whose mothers were HBsAg-positive, while IL-12 might inhibit the immune response. IL-6 and IL-12 would affect the immune response to hepatitis B vaccination in infants of HBsAg-positive mothers at the same time.

Objective: To explore the effect of telbivudine treatment in a prevention program on infants born to HBsAg-positive mothers with non-/hypo-responsiveness to hepatitis B vaccine. Methods: A retrospective cohort study with a total of 321 HBsAg-positive pregnant women and their infants enrolled, was conducted. The mothers were recruited from the Third People' s Hospital of Taiyuan, from July 2011 to January 2013. According to the situation of telbivudine intake in second and third trimesters of pregnancy, the participants were divided into two groups: with telbivudine-treated or as control. The neonates were followed up till the age of 12 months. Maternal, neonatal and infantile HBV-M together with HBV DNA in serum were measured using the electro-chemiluminescence immuno-assay (ECLIA) kits and fluorescence quantitative polymerase chain reaction (FQ-PCR) assay, respectively. Results: The rate of non-/hypo-response was 17.99%. After adjusting the potential confounding factors, the telbivudine treatment on HBsAg-positive mothers in the second and third trimesters of pregnancy seemed as the protective factor for non-/hypo-response to hepatitis B vaccine in infants (a RR =0.119, 95 % CI : 0.014-0.974). Levels of IFN-γ and IL-10 in telbivudine-treated group were higher than those in the controls (a RR =8.684, 95 %CI : 1.977-38.140; a RR =5.330, 95 % CI : 1.278-22.236). When the serum levels of IFN-γ and IL-10 in neonatal peripheral blood were higher than 228.47 pg/ml and 174.05 pg/ml respectively, the infants were less likely to be non-/hypo-responsive to the hepatitis B vaccine (a RR =0.300, 95 %CI : 0.105-0.857) (a RR = 0.104, 95 % CI : 0.030-0.354). Conclusion: Telbivudine treatment provided for the HBsAg-positive mothers in second and third trimesters of pregnancy were less likely to develop non-/low-responsive to hepatitis B vaccine in infants since IFN-γ and IL-10 might have played a vital role in this process.

Objective: A prospective study was conducted to explore the influence of neonatal modes of HBV marker (HBVM) on non-/hypo-response to hepatitis B vaccine in infants., Methods: From July 2011 to July 2013, a total of 386 pregnant women who showed serum HBsAg positive with their neonates at birth and another 227 infants at 12 months admitted in the Third People' s Hospital of Taiyuan in Shanxi province, China. All infants received hepatitis B vaccine with the 0-1-6 month schedule. Maternal, neonatal and infantile HBsAg, anti-HBs, HBeAg, anti-HBe and anti-HBc were measured by chemiluminescence-immunoassay. The neonatal/infantile PBMC TLR3 expression level and the quantities of T cell subsets, B cells, DCs were measured by Flow Cytometry. The neonatal/infantile Th1/Th2 cytokines were measured by ELISA., Results: Four types of common neonatal modes of HBVM appeared as " HBeAg(+) anti-HBe(+) " , "HBsAg(+)HBeAg (+) anti-HBe(+) " , "HBsAg(+) " and "HBVM(-)" , respectively. The overall rate of non-/hypo-response to hepatitis B vaccine in neonatal mode of " HBeAg(+) anti-HBe(+) " was 5.2%, lower than that seen in the other three types of mode (20.0%, 40.0% and 22.5%, respectively). The frequencies of circulating CD4(+) T cells and CD8(+) T cells were significantly different among four common modes of HBVM in infants. Meanwhile, the level of IL-6 in mode of " HBeAg(+) anti-HBe(+) " was higher than that in the mode of " HBVM(-)" at two points. There was a positive correlation appeared between the level of IL-6 and the level of anti-HBs. It was quite unlikely to show non-/hypo-response to hepatitis B vaccine, when neonates were at the level as IL-6> 1 112.0 pg/ml (OR=0.386, 95% CI: 0.266-0.561, P<0.001)., Conclusions: Neonates who were with the mode of " HBeAg (+) anti-HBe (+) " and high level of IL-6 showed a lower non-/hyporesponse rate on hepatitis B vaccine. It is necessary to further study the relationship between neonatal mode of HBVM and the immune status.