Efficacy and safety of telbivudine and tenofovir disoproxil fumarate in preventing hepatitis B vertical transmission: A real-life practice.

Mother-to-child transmission (MTCT) is a major obstacle in the elimination of hepatitis B virus (HBV) infection. Telbivudine (LdT) and tenofovir disoproxil fumarate (TDF) are the two most common antiviral medicines for preventing MTCT. However, the efficacy and safety of LdT and TDF in preventing HBV vertical transmission during the second to third trimester have not been compared rigorously. Therefore, we carried out a prospective multicentre cohort study of chronic hepatitis B in mothers with HBV DNA > 106  IU/mL, receiving LdT or TDF during the second to third trimester. Among the 893 mothers enrolled, 857 (LdT/TDF/untreated group (NTx) = 396/325/136) completed consecutive follow-up with 854 infants (LdT/TDF/NTx = 395/323/136). LdT and TDF treatment resulted in a similar decrease of HBV DNA in mothers at delivery. Multivariate analysis indicated that only HBsAg titre at the baseline correlated with viral DNA decrease (P = 0.015). With intention-to-treat analysis, MTCT rates in the LdT, TDF and NTx group were 4.41%, 2.42% and 22.08%, respectively. An increasing vertical transmission rate was found to be closely associated with higher HBsAg titre, 5.32% and 17.65% infection rate was estimated in infants born to mothers with HBsAg > 4 and >5 log10 IU/mL, respectively. No serious side effects were reported in either mothers or infants. LdT and TDF treatments were well tolerated and showed comparable efficacy in reducing MTCT. Higher risk of MTCT was shown in pregnant women with HBsAg > 4 log10 IU/mL.

Baseline Hepatitis B Virus Titer Predicts Initial Postpartum Hepatic Flare: A Multicenter Prospective Study.

BACKGROUND AND GOALS: A series of changes in the immune system occur during pregnancy and puerperium. Currently, we aim to characterize both the natural changes in liver inflammation and its association with hepatitis B viremia during this special period. PATIENTS AND METHODS: Chronic hepatitis B (CHB) gravidas were recruited and followed up to 52 weeks postpartum. Virological and biochemical parameters were assessed throughout the period. RESULTS: A total of 1097 CHB mothers had finished the entire follow-up including 451 accepting telbivudine, 178 accepting tenofovir, and 468 without antiviral therapy. Among the mothers, 11.94% went through hepatic flare in the first trimester and the rate decreased to 2.1% at the time of delivery. Nevertheless, a much higher frequency (19.78%) was observed in the early postpartum. Interestingly, alanine aminotransferase level decreased along with the development of pregnancy and then suddenly increased in the first month of puerperium. In addition, a downward trend was observed on the titer of HBsAg and HBeAg after delivery. Of note, an obvious higher frequency of alanine aminotransferase flare was revealed in mothers with high viremia (>6 log10 IU/mL). With multivariate analysis, only hepatitis B virus titer at baseline was strongly associated with hepatic flare during early postpartum (95% confidence interval, 1.012-3.049, P=0.045). The predictive rates of hepatic flare at baseline viral load of 6, 7, and 8 log10 IU/mL were 16.67%, 28.30%, and 30.60%, respectively. CONCLUSIONS: CHB gravidas with high viremia should be monitored closely during entire pregnancy, and extended antiviral therapy is recommend to those mothers with baseline viremia >7 log10 IU/mL.

Hepatic flare after telbivudine withdrawal and efficacy of postpartum antiviral therapy for pregnancies with chronic hepatitis B virus.

BACKGROUND AND AIM: The efficacy of telbivudine for breaking vertical transmission of hepatitis B virus has been well established. Data on the risk of postpartum flare after telbivudine withdrawal and efficacy of extended antiviral therapy after delivery are limited. METHODS: Chronic hepatitis B virus-infected women who received telbivudine beginning at week 24 or 28 of gestation were enrolled and then followed up to 52 weeks postpartum. Virological and biochemical parameters were assessed. RESULTS: Of the 241 women who finished 52 weeks of follow-up, 33.6% had elevated serum alanine aminotransferase (ALT) during pregnancy. Telbivudine administration resulted in ALT normalization in 85.2% before delivery. Compared with women having a normal ALT level throughout pregnancy, those with elevated ALT had a significantly higher rate of ALT flare after telbivudine withdrawal (25.0% vs 11.9%; χ2 = 4.273, P = 0.039). Multivariate analysis indicated that only ALT elevation during pregnancy correlated with postpartum flare after telbivudine withdrawal. Those women with elevated ALT during pregnancy continued antiviral treatment to 52 weeks postpartum and had a significantly higher HBeAg seroconversion rate (P = 0.001) and a notable decrease in HBsAg titers (P = 0.001). CONCLUSION: It is safe for the majority of women to withdraw telbivudine after delivery, whereas exciting serological response encourages extended antiviral therapy for mother with ALT elevation during pregnancy.

Different interventional criteria for chronic hepatitis B pregnant women with HBeAg(+) or HBeAg(-): Epidemiological data from Shaanxi, China.

The seroprevalence of hepatitis B virus (HBV) and its impact on pregnancy outcomes of women from Shaanxi Province (China) was assessed. Risk factors for mother-to-child transmission (MTCT) were evaluated based on HBV-related seroprevalence data.Viral markers and biochemical parameters were assessed in HBsAg-positive mothers and their infants out of 13,451 cases recruited. A pretested and structured questionnaire was used to test the general HBV knowledge. Descriptive statistics and logistic regression analysis were done to reveal possible risk factors for MTCT.The overall prevalence of HBsAg in pregnant women was 7.07% (951/13,451), and a rate as high as 9.40% was observed. Among the HBsAg-positive pregnant women, 30.49% (290/951) were HBeAg-positive, 22.08% (210/951) had HBV DNA levels >10 IU/mL and only 16.19% with a high risk of MTCT (34/210) had received antiviral treatment. The overall MTCT rate was 5.21%. Noteworthy, the risk ratio and 95% confidence interval (95% CI) of MTCT in HBeAg-negative mothers with HBV DNA levels >2 × 10 IU/mL and HBsAg >10 IU/mL was 26.062 (2.633-258.024), which was significantly higher than that of HBeAg-positive mothers with HBV DNA level >10 IU/mL. Moreover, the awareness and knowledge about HBV transmission, risk factors, and intervention for MTCT were generally lacking among HBsAg-positive mothers.As a higher HBsAg seroprevalence and a higher MTCT rate among HBeAg-negative mothers with lower HBV DNA level was observed, our study emphasizes different interventional criteria for HBeAg-positive and HBeAg-negative mothers. Extensive health education, routine screening, and immunization against HBV during pregnancy are highly warranted to minimize the possibility of perinatal transmission.

Efficacy of tenofovir disoproxil fumarate to prevent vertical transmission in mothers with lamivudine-resistant HBV.

BACKGROUND: In China, women with chronic HBV infection and who are of childbearing age receive lamivudine at an early age. Thus, viral resistance becomes a challenge for intervention to prevent mother-to-infant transmission. We prospectively assessed the efficacy of tenofovir in pregnant women with lamivudine-resistant HBV. METHODS: Chronic HBV-infected mothers resistant to lamivudine were enrolled. Tenofovir was administrated at gestation weeks 24 or 28. Virological and biochemical parameters were assessed. All infants received combined immunoprophylaxis and were followed for 1 year. RESULTS: Of the 48 mothers enrolled, 21 started tenofovir therapy at gestation week 24 and 27 started at week 28. Tenofovir resulted in an HBV DNA decline of 5.23 ± 1.68 log10 IU/ml at delivery. The group starting therapy at week 24 exhibited a more rapid viral inhibition (P<0.001) and more significant HBV DNA load decline (5.89 ± 1.66 versus 4.72 ± 1.55; P=0.019) than the group starting at week 28. At delivery, all mothers had a viral titre <10(6) IU/ml, 76.2% from the week 24 starting group displayed virus <10(4) IU/ml, and 52.4% showed undetectable virus at delivery, much higher than the week 28 starting group (29.6%), although there was no statistically significant difference in viral levels at delivery between the two groups. Congenital abnormalities and neonatal growth were comparable to the normal population. No case of perinatal transmission was diagnosed. CONCLUSIONS: This investigation clarifies the efficacy of tenofovir for reducing vertical transmission of HBV in mothers with lamivudine-resistant HBV and demonstrates that tenofovir is well-tolerated in the second and third trimesters.