Objective To explore the relationship between hepatitis B virus (HBV) S gene variation,genetype and immunoprophylaxis failure to intrauterine infection of HBV.Methods The serum HBV DNA levels of 35 pairs of mother-infants were amplified and quantified by real-time fluorescent quantitative polymerase chain reaction (PCR).Thereafter,the sequences of HBV S gene were determined by sequencing and compared with Genbank standard sequence using DNASTAR software.Results HBV DNA levels of the 35 pairs of mother-infants were all above 1×106 copy/mL.Nucleotide diversity rates were 11.4% in the children and 17.1% in their mothers.The sequence homology between paired mother and infant was beyond 99.3%.The HBV genotype and serotype in 23 pairs of mother-infants was C and adr respectively,while that was B and adw in the other 12 pairs.The HBV genotype and serotype were identical between paired mothers and infants.Conclusions HBV S gene variation may not be a crucial factor for immune failure to HBV intrauterine infection in women with high level viremia.Genotyping could not predict and evaluate the risk of immunoprophylaxis failure to HBV intrauterine infection in neonates.

Objective:To compare the efficacy and safety of telbivudine (LDT) and tenofovir disoproxil fumarate (TDF) treatment during the second and third trimester in pregnant women with high viral load of hepatitis B virus (HBV).Methods:Totally 506 pregnancy women with HBV infection who received antiviral therapy during the second and third trimester of pregnancy in the obstetrical clinic of The Affiliated Nanjing Hospital of Nanjing University of Chinese Medicine from January 1, 2016 to December 31, 2018 were retrospectively enrolled, and the anti-viral efficacy and safety in mothers and neonates were evaluated. Pregnancy women were divided into TDF group and LDT group according the medications. The efficacies including decline and negative rate of HBV DNA, the vertical transmission (VT) rate, the normalization rate of liver function in mothers between the two groups were compared. The safeties including birth weight of neonates, congenital deformities and the rates of preterm between the two groups were also compared. Chi-square test, independent sample t test or rank sum test were used for statistical analysis. Results:There were 239 pregnant women in the LDT group and 267 in the TDF group. The maternal HBV DNA levels before treatment in the LDT and TDF groups were (7.83±0.75) lg IU/mL and (7.82±0.66) lg IU/mL, respectively, while the maternal HBV DNA levels prior to delivery were 2.91(1.20) lg IU/mL and 2.83(1.01) lg IU/mL, respectively. The normalization rates of alanine aminotransferase (ALT) of chronic hepatitis B (CHB) pregnant women prior to delivery in TDF group and LDT group were 95.00%(38/40) and 98.18%(54/55), respectively. There were all no significant differences between the two groups ( t=0.097, U=1.040 and χ2=0.767, respectively, all P>0.05). For CHB pregnant women, the HBV DNA negative rate at one month postpartum in TDF group was 85.45%(47/55) and that in LDT group was 82.50%(33/40). The normalization rate of ALT in TDF group was 94.55%(52/55), and that in LDT group was 92.50%(37/40). There were no significant differences between the two groups ( χ2=0.152 and 0.164, respectively, P=0.697 and 0.687, respectively). The VT rates were 0(0/262) in TDF group and 0.43%(1/231) in LDT group, which had no significant difference between the two groups ( χ2=1.127, P=0.288). Two patients in LDT group who continued taking LDT 11 months postpartum switched to TDF because of HBV rt204 mutation, and no one had virus mutation in TDF group. No significant increased in creatine kinase in LDT group, and no significant abnormal calcium and phosphorus metabolism in the TDF group. The preterm rate was 7.87%(21/267) in TDF group and 4.18%(10/239) in LDT group, but there was no significant difference between the two groups ( χ2=2.970, P=0.085). However, the birth weight of neonates in TDF group ((3 204.72±490.50) g) was lower than that in LDT group ((3 374.31±467.50) g), and the difference was statistically significant ( t=3.780, P<0.01). During the course of treatment, no pregnant women discontinued treatment due to drug intolerance, and no infants presented with drug-related birth defects. Safeties for mothers and neonates were both good. Conclusions:Both LDT and TDF treatment could reduce the VT rate in pregnant women with high HBV viral load. The safety is good for both mothers and neonates. However, for CHB pregnant women who continue antiviral therapy postpartum, TDF is superior to LDT because of lower virus mutation, thus to reduce the risk of drug resistance.

Objective:To investigate the characteristics of HBV-specific T cell reactivity among pregnant, postpartum and non-pregnant women at childbearing age with chronic HBV infection.Methods:A total of 100 patients with chronic HBV infection were enrolled in this study, including 43 pregnant women (pregnant group), 26 patients giving birth within six months (postpartum group), and 31 non-pregnant patients at childbearing age (non-pregnant group). The functional HBV-specific T cells in peripheral blood were detected by ELISPOT. Clinical data as well as the results of virological and serological tests of HBV were collected for stratified analysis.Results:There was no significant difference in the number of functional HBV-specific T cells between the pregnant group and the postpartum group, but the number was significantly lesser in the pregnant group than in the non-pregnant group ( P<0.05). Furthermore, the number of functional HBV-specific T cells was significantly higher in the nucleoside analogues (NUCs)-treated pregnant women than in the NUCs-untreated pregnant women ( P<0.05). Among the patients without NUCs treatment, there were no significant differences in the numbers of hepatitis B envelope antigen/hepatitis B core antigen (HBeAg/HBcAg)-specific T cells between the pregnant group and the postpartum group, but the numbers were lower in the pregnant group than in the non-pregnant group ( P<0.05). Among the NUCs-treated patients, there was no significant difference in the number of functional HBV-specific T cells between the pregnant group and the non-pregnant group, and the numbers in the two groups were significantly higher than that in the postpartum group (both P<0.05). Additionally, receiver operating characteristic (ROC) curve indicated that the number of functional HBV-specific T cells in combination with HBV DNA load [area under the curve (AUC)=0.807] or hepatitis B surface antigen (HBsAg) levels (AUC=0.916) had a good predictive performance for hepatitis progression during pregnancy. Conclusions:Pregnancy can reduce HBV-specific T cell reactivity in women with chronic HBV infection, but NUCs treatment may improve the function of specific T cells. Routine monitoring of HBV-specific T cells during pregnancy and postpartum period can provide valuable guidance for the evaluation of immune function and treatments.