Administering tenofovir to pregnant women with a hepatitis B virus (HBV) high viral load during the 2nd or 3rd trimester reduced rates of mother-to-child transmission (MTCT), according to a study by researchers at Korea University Medical Centre, Seoul, Korea.
In regions of the world with widespread HBV infection, the majority of infections are caused by MTCT. Combined newborn vaccination and immunoprophylaxis programs have lowered the rate of MTCT from 90% to 10%. However, this strategy fails up to 30% of the time in the setting of high maternal viral DNA levels (>106 copies/mL) and positive maternal hepatitis B envelope antigen (HBeAg).
Several oral antiviral agents are effective for preventing MTCT when administered during pregnancy. Lamivudine and telbivudine reduce the risk of MTCT without a significant increase in adverse events, but their use is hampered by the high risk of developing resistance to these agents. Tenofovir has a higher threshold for resistance and is the preferred agent for preventing MTCT. However, the data for tenofovir use in this setting are limited and include only 1 randomised controlled trial (RCT), which alone may not be sufficient to support the use of tenofovir to prevent MTCT.
Researchers conducted a meta-analysis of the available randomised and non-randomised studies to evaluate the safety and efficacy of tenofovir during the 2nd or 3rd trimester for reducing the risk of MTCT in pregnant women with high HBV viral load.
A total of 10 studies (n=733 pregnant women), including 1 RCT, were included for analysis. The HBV vaccine and HBV immunoglobulin were administered at birth to all infants in the studies.
Of 599 pregnancies from 5 comparative trials, infants born to mothers receiving tenofovir were 77% less likely to have hepatitis B surface antigen (HBsAg) seropositivity than infants whose mothers did not receive tenofovir (odds ratio [OR], 0.23; P =.0004).1
Rates of maternal adverse events (elevated alanine aminotransferase [ALT]) and foetal adverse events (congenital malformation and fetal death), were similar between the tenofovir and control groups.
In the analysis of 5 case series (n=134 pregnant women), there were only 2 instances (1.5%) of MTCT, and these were characterised by extremely high maternal viral load (152,000,000 copies/mL) and treatment non-adherence. The overall rate of serious adverse events, which included post-partum haemorrhage and hypospadias, (3%) was low. There were no instances of fetal death.
“In conclusion, tenofovir therapy in HBV-infected mothers in the second or third trimester efficiently interrupts MTCT, as indicated by infant serum HBsAg positivity. Tenofovir treatment is safe and tolerable for both the mother and f[o]etus. Clinicians who manage pregnant patients with high hepatitis B viral loads should consider tenofovir therapy to prevent MTCT in addition to immunoprophylaxis combination therapy,” the researchers wrote.
Background: Preventing mother to child transmission of chronic hepatitis B infection in the setting of a high maternal viral load is challenging. The idea has emerged from antepartum tenofovir treatment with combination immunoprophylaxis.
Aims: To demonstrate the efficacy and safety of tenofovir to prevent mother to child transmission of hepatitis B virus.
Methods: PubMed, EMBASE, and Cochrane databases were searched through August 16, 2016. Comparative trials of second or third trimester tenofovir administration vs. controls for patients with chronic hepatitis B infection and non-comparative case series assessing mother to child transmission rates and evaluating maternal and foetal safety outcomes were included.
Results: Ten studies (one randomised controlled trial, four non-randomised controlled trials and five case series) that enrolled 733 women were included. The pooled results from comparative trials (599 pregnancies) showed that tenofovir significantly reduced the risk of infant hepatitis B surface antigen seropositivity by 77% (odds ratio=0.23, 95% confidence intervals=0.10-0.52, P=.0004) without heterogeneity (I2=0%). In the case series analysis (134 pregnancies), only two cases (1.5%) of mother to child transmission with extremely high maternal viral load and non-compliance to treatment were identified. Maternal and foetal safety parameters including congenital malformation and foetal death were re-assuring.
Conclusions: For pregnant women with high hepatitis B virus DNA levels, tenofovir administration in the second or third trimester can prevent mother to child transmission when combined with hepatitis B immunoglobulin and the hepatitis B vaccine. Tenofovir is safe and tolerable for both the mother and foetus.
MH Hyun, YS Lee, JH Kim, JH Je, YJ Yoo, JE Yeon, KS Byun