Efficacy and Safety of Antiviral Treatment on Blocking the Mother-to-child Transmission of Hepatitis B Virus

A Meta-analysis

Jiahui Song; Fan Yang; Shuo Wang; Sakinatou Tikande; Yang Deng; Weina Tang; Guangwen Cao


J Viral Hepat. 2019;26(3):397-406. 

In This Article

Abstract and Introduction


Nucleo(t)side analogues (NAs) have been administered as adjunctive therapy to interrupt the mother-to-child transmission (MTCT) of hepatitis B virus (HBV). The efficacy and safety of this method remain controversial. A meta-analysis was conducted to evaluate the efficacy and safety of NAs treatment during pregnancy. The differences among different agents and initiation trimesters were analysed. A total of 9228 mother-infant pairs in 59 studies (32 RCTs and 27 non-RCTs) were included in this meta-analysis. NAs significantly reduced the risk of MTCT, as indicated by seropositivity of hepatitis B surface antigen (HBsAg) (risk ratio (RR) = 0.51, 95% confidence interval (CI) 0.45-0.57) and HBV DNA in newborns (RR = 0.22, 95% CI 0.18-0.26). No differences in the efficacy of interrupting HBV MTCT were evident among lamivudine, telbivudine and tenofovir disoproxil fumarate. NA was more effective when administered from the second than from the third trimester as indicated by HBV DNA (RR: the second vs the third 0.08 vs 0.22, P = 0.010), but this effect was not evident as indicated by HBsAg (RR: the second vs the third 0.46 vs 0.53, P = 0.596). Antiviral treatment initiated from the second trimester did not confer a higher risk of safety problems in the newborns compared with treatment from the third trimester, as indicated by weight (P = 0.064), length (P = 0.491) and malformation rate (P = 0.635) of newborns.

Conclusions: Lamivudine, telbivudine and tenofovir disoproxil fumarate are equally effective in blocking HBV MTCT. Antiviral treatment can be applied from the second trimester, without obvious safety concerns.


Chronic hepatitis B virus (HBV) infection contributes to more than half of global primary liver cancer, the second most common cause of cancer death in males.[1] It is estimated that there are more than 240 million chronic HBV carriers globally, half of which are attributable to HBV mother-to-child transmission (MTCT).[2] In highly endemic areas, HBV infection during infancy and early childhood via MTCT is a prominent risk factor for developing chronic infection (more than 50%) as well as cirrhosis or primary liver cancer (approximately 25%).[1] The World Health Organization (WHO) plans to achieve a 90% reduction in new cases of chronic HBV and hepatitis C virus (HCV) infection and a 65% reduction in mortality by 2030.[3] To achieve this goal, blocking HBV MTCT is essential to reduce the number of new HBV carriers and HBV-related deaths.

Recently, combined use of hepatitis B immunoglobulin (HBIG) and hepatitis B vaccine (HBVac) was recommended by WHO to interrupt the vertical transmission of HBV. According to a deterministic mathematical transmission modelling study, approximately 210 million infants had been protected from HBV infection, owing to the application of the HBVac, by the year 2015.[4] However, the MTCT is more likely to occur in pregnant women with high viral load (HBV DNA > 106 IU/mL) and no antiviral treatment, even if both HBIG and HBVac immunizations have been applied, namely, interruption failure.[5,6] Nucleo(t)side analogues (NAs), the most widely used orally administered agents against HBV, are expected to reduce the chance of vertical transmission via inhibiting the replication of maternal HBV. Among all the NAs now applied in clinical practice, adefovir dipivoxil and entecavir are not recommended for pregnant women, due to teratogenicity and lethality observed in animal experiments,[7,8] while lamivudine (LAM), telbivudine (LdT) and tenofovir disoproxil fumarate (TDF) are more commonly applied in clinical practice. However, their efficacy and safety remain the major concern. To the best of our knowledge, no NA is formally approved, due to lack of evidence confirming their benefit and safety during pregnancy. Clinical trials with relatively small sample size are insufficient to provide robust evidence for evaluating the efficacy and safety of antiviral agents. Here, we performed a meta-analysis to evaluate the efficacy and safety of LAM, LdT and TDF on the prevention of HBV MTCT.