A new study published in the New England Journal of Medicine has shown that tenofovir disoproxil fumarate (TDF) treatment during pregnancy can reduce the incidence of mother-to-child transmission of hepatitis B virus.
Chronic hepatitis B virus (HBV) infection continues to be a serious public health issue and is associated with liver cancer and cirrhosis. Although long-term antiviral treatment can reduce the incidence of liver cancer and the severity of cirrhosis, the elimination of HBV is unlikely. Accordingly, the most effective way to minimize the worldwide burden of HBV infection and liver cancer is the prevention of transmission of HBV.
Chronic HBV can be transmitted from a pregnant mother infected with the virus to their infant during pregnancy, at the time of delivery, or during the first 28 days after birth. Studies show that the risk-of-mother to child transmission of HBV increases as the maternal viral load (amount of virus in the body) increases, although transmission is much less likely when the maternal HBV viral load at delivery is lower than 200, 000 IU (international units) per mL than when the level is 200, 000 IU or greater per mL.
When untreated, 80% to 90% of infants born to mothers who are hepatitis B e antigen (HBeAg) positive develop chronic HBV infection. The incidence of mother-to-child transmission decreases from 90 to 10 percent with the combination of postnatal passive and active immunization (immunoprophylaxis). However, immunoprophylaxis has a failure rate of 10% to 30% in infants born to mothers with an HBV viral load of over ~180, 000 IU per mL. This amount is present in many cases of mother-to-child transmission in regions where HBV is regularly found and further increases the worldwide incidence of chronic HBV infection. A small but increasing body of research suggests that the risk of mother-to-child transmission in mothers with an HBV viral load of over ~180 000 IU per mL or more may be reduced with antiviral treatment, particularly tenofovir disoproxil fumarate (TDF), although these studies were of low quality and showed results that are conflicting.
A group of researchers investigated the efficacy and safety of TDF therapy in preventing mother-to-child transmission of chronic HBV infection by conducting a randomized, controlled trial. The trial comprised of 200 mothers in China who were HBeAg positive and had an HBV viral load above 200, 000 IU per mL. Participants were randomly assigned to receive TDF (an oral dose of 200 mg per day) or to receive usual care without antiviral treatment from 20 to 32 weeks of gestation until 4 weeks after delivery. The participants were followed until 28 weeks postpartum. Immunoprophylaxis was received by all infants.
The findings, published in The New England Journal of Medicine, show that mother-to-child transmission of HBV is reduced with TDF therapy during the third trimester in pregnant chronic HBV mothers with a high viral load (more than 200, 000 IU per mL). The researchers found that 68% of the mothers treated with TDF, as compared with 2% who received usual care without antiviral treatment, had the target HBV viral load (less than 200, 000 IU per ml) at delivery, which suggests that TDF decreased maternal viremia (presence of virus in the blood).
Moreover, TDF was effective in reducing the rate of mother-to-child transmission at postpartum week 28, as demonstrated by both the intention-to-treat analysis and the per-protocol analysis. In the intention-to-treat analysis, which comprised of all women except those who withdrew consent before the start of treatment, the rate of mother-to-child transmission at 28 weeks was considerably reduced with TDF treatment, with transmission of virus reduced to 5%, compared to 18% of infants born to mothers who received usual care with antiviral therapy. Similarly, in the per-protocol analysis, which excluded mothers who withdrew consent, discontinued treatment for any reason or were lost to follow-up, the rate of mother-to-child transmission was 0% for infants born to mothers treated with TDF and 7% for infants of women not given antiviral therapy.
The researchers also reported on safety profiles of mothers, which were comparable in the TDF group and the control group, including rates of birth-defect, even though more mothers in the TDF group had increased levels of creatine kinase during treatment (7% vs 0%) and increased levels of alanine aminotransferase after discontinuation of treatment (45% vs 30%). Safety profiles in infants were similar between infants whose mothers were treated with TDF and those whose mothers were not, including the rate of congenital defects or deformities (2% vs 1%).
In conclusion, the study demonstrates that mothers, with an HBV viral load of more than 200, 000 IU per mL at 28 weeks gestation and who receive TDF treatment, have a lower incidence of mother-to-child transmission of hepatitis B virus, compared to mothers who do not receive antiviral therapy. Overall, the findings suggest that TDF may be useful for preventing mother-to-child transmission, which is an important step toward the worldwide eradication of hepatitis B virus and a reduction in the rate of liver cancer.
Written By: Nigar Celep, BASc