COMMENTARY

New Strategies for Preventing Perinatal Transmission of Hepatitis B Virus

William F. Balistreri, MD

Disclosures

November 14, 2017

New Strategies for a Persistent Problem

Acute and chronic hepatitis due to either hepatitis B virus (HBV) or hepatitis C virus (HCV) infection has surpassed HIV to become the seventh leading cause of death worldwide.[1] These infections account for more than 1 million deaths globally per year and 78% of the cases of hepatocellular carcinoma.[1] This is tragically ironic, as we now have the tools to prevent HBV and cure HCV.

The good news is that comprehensive and aggressive strategies for reduction of viral hepatitis have recently been proposed, such as those from the National Academies of Sciences, Engineering, and Medicine.[1] This proposal notes that perinatal transmission accounts for a significant percentage of cases of both HBV and HCV. Therefore, universal screening programs and timely intervention can break these mother-to-infant cycles and greatly assist efforts to reduce the global burden of infection.[2]

Strategies dedicated to early detection of HBV infection to establish targeted medical intervention are key to improving maternal and neonatal outcomes.

We previously reviewed the rationale for and issues related to efforts to prevent transmission of HBV infection in the perinatal period. We illustrated the issue with the following case scenario:

A 20-year-old woman in the first trimester of pregnancy is found to be positive for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg). Subsequent testing indicates that she has high serum levels of HBV DNA, with normal serum alanine aminotransferase (ALT) levels and no clinical evidence of hepatosplenomegaly. The patient has questions about how to prevent perinatal transmission of HBV to her infant. Specifically, she requests information about the success of immunoprophylaxis with HBV vaccine and high-titer anti-HBs immunoglobulin (HBIg). She also requests information about the potential use of antiviral therapy. Will this reduce the risk to the infant? What is the effect on her disease?

After this discussion, the mother received an antiviral drug in the third trimester of her pregnancy; her infant, now 18 months old, remains uninfected.

Since that time, the strategy for antiviral administration to prevent perinatal transmission has been endorsed by several groups. The published data and experiences that served as the basis for the newly recommended approach are reviewed herein.

Adverse Effects Persist Despite Current Strategies

To reduce the incidence of perinatal transmission of HBV, the American Academy of Pediatrics and the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention recommend that all newborn infants receive HBV vaccine by 24 hours of age.[2] Infants born to mothers who are HBsAg positive require prompt administration of vaccine along with HBIg. They also urge postvaccination serologic testing (HBsAg and anti-HBs) of infants (at age 9-12 months) born to HBsAg-positive women in order to assess the response of the infant to vaccination.[3]

Despite timely postexposure prophylaxis, as recommended, perinatal HBV transmission occurs in 5%-15% of infants. HBeAg-positive mothers with high HBV DNA levels are at greatest risk of transmitting HBV to their infants.[4] The rate of immunoprophylaxis failure closely correlates with the maternal predelivery HBV DNA level (approximately 3% for levels >106 copies/mL, 7% for levels >107 copies/mL, and 8% for levels >108 copies/mL).[4,5,6] No perinatal transmission has been reported in infants born to mothers with viral loads <106 copies/mL. Quantitative maternal HBsAg levels, which are positively correlated with maternal HBV load, also accurately predict the risk for perinatal transmission of HBV infection.[7]

Cheung and colleagues[6] recently reported the success of standard immunoprophylaxis for infants born to HBeAg-positive mothers. All newborns received HBV vaccine and HBIg intramuscularly within 12 hours of birth and subsequent doses of vaccine at 1 and 6 months. Seven infants born to the HBeAg-positive women had immunoprophylaxis failure, and t heir mothers had markedly elevated levels of HBV DNA. Infants born to mothers with lower HBV DNA levels had no risk for immunoprophylaxis failure.

In addition to transmission of viral infection, several recent studies indicate other potential adverse outcomes of pregnancies complicated by maternal HBV infection.[8,9] Wan and colleagues[8] found that maternal HBV carriage was associated with an increased risk for pregnancy-induced hypertension, fetal distress, cesarean delivery, and infant macrosomia. In addition, the maternal viral load in the second trimester was significantly associated with risk for preterm birth among HBsAg carriers.[8] Similarly, Liu and colleagues[9] reported that women who were HBsAg positive and HBeAg negative had an 18% higher risk for early preterm birth, which was elevated to 34% in those who were both HBsAg and HBeAg positive.

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