New Strategies for Preventing Perinatal Transmission of Hepatitis B Virus

William F. Balistreri, MD


November 14, 2017

Latest on Antiviral Agents

These data strongly suggest that, in a subset of HBV-infected women, additional preventive measures may be required; specifically, administration of antiviral agents during the third trimester.

Multiple studies have been conducted to determine the effect of reduction of the maternal viral load through administration of antiviral therapy in the third trimester, thereby limiting exposure of the neonate to HBV.[10,11,12,13] Several therapeutic options are available: lamivudine,[14,15,16]telbivudine,[17,18,19,20,21] and tenofovir disoproxil fumarate.[22,23,24,25] Administration of each of these agents has been associated with significant reductions in maternal viral loads and in the rates of perinatal HBV transmission, with favorable safety profiles.[26] Each offers distinct advantages and disadvantages.

Zhang and colleagues[27] randomly assigned HBeAg-positive mothers with a serum HBV DNA level >106 copies/mL to receive telbivudine, lamivudine, or no treatment at gestation week 28 until postpartum week 4. At delivery, HBV DNA levels were significantly lower in mothers who received antiviral therapy. None of the infants in the treated groups (compared with 3% in the untreated group) became HBsAg positive. The treatment was well tolerated, with no safety concerns identified.

Yu and colleagues[28] compared the efficacy and safety of telbivudine vs lamivudine in HBeAg-positive women. Perinatal HBV transmission did not occur, and there were no instances of immunization failure in infants born to mothers who received either antiviral agent compared with 5% in the control group.

Greenup and colleagues[23] conducted a multicenter, prospective, observational comparison study of antiviral safety and efficacy in pregnant women with high HBV DNA titers (≥107 copies/mL). Viral load declined, and the rate of perinatal transmission was reduced significantly to 2% (tenofovir) and 0% (lamivudine) compared with 20% in the untreated cohort.

Pan and colleagues[29] randomly assigned 200 HBeAg-positive mothers who had an HBV DNA level >200,000 IU/mL to receive either usual care (no antiviral therapy) or oral tenofovir (300 mg/day) from 30 to 32 weeks of gestation until postpartum week 4. All of the infants also received standard immunoprophylaxis. At delivery, 68% of the mothers in the tenofovir group had an HBV DNA level of <200,000 IU/mL compared with 2% in the control group. At postpartum week 28, the rate of mother-to-child transmission was significantly lower in the tenofovir recipients than in the control group (5% vs 18%).

Hyun and colleagues[30] searched literature databases to determine the efficacy and safety of tenofovir to prevent mother-to-child transmission of HBV. Ten studies (733 women) were included, the pooled results of which showed that tenofovir reduced the risk for infant HBsAg seropositivity by 77% and was safe and tolerable for both the mother and fetus.

American Association for the Study of Liver Diseases Guidelines

The American Association for the Study of Liver Diseases (AASLD) recommends antiviral therapy to reduce the risk for perinatal transmission of HBV in HBsAg-positive pregnant women with an HBV DNA level >200,000 IU/mL.[31] Their report cites 11 controlled studies, which enrolled 1504 mother-infant pairs to examine the use of any antiviral therapy in the third trimester. Few studies were randomized, double-blind, controlled clinical trials.

They found no high-quality evidence comparing these antiviral agents. The guidelines note that in most published studies, antiviral therapy was started at 28-32 weeks of gestation and was discontinued at birth to 3 months postpartum. They recommended that following discontinuation of treatment, women should be monitored for ALT flares every 3 months for 6 months. In their assessment, breastfeeding is not contraindicated, as these antivirals are minimally excreted in breast milk and are unlikely to cause significant toxicity.

Is Gestational Antiviral Therapy Safe and Cost-Effective?

The potential for widespread application of the strategy of third-trimester antiviral administration raises several concerns, such as the effects on the growth and development of the infant and the potential for flares of maternal hepatitis after drug discontinuation. In addition, the cost of antiviral therapy may be prohibitive in developing countries where HBV is endemic.[12,13,32]

Zeng and colleagues[33] reported that growth and development were normal in children who were prenatally exposed to telbivudine used to treat chronic HBV infection in their mothers. The Antiretroviral Pregnancy Registry reports no evidence of adverse outcomes in infants born to mothers who have been treated with lamivudine, tenofovir, or telbivudine during pregnancy; administration of these agents did not result in an increased incidence of birth defects.[34] The safety of entecavir in pregnancy is not known, and interferon therapy is contraindicated.

Fan and colleagues[35] used a decision tree and Markov model to estimate the cost-effectiveness of three strategies:

  1. Current strategy: All pregnant women are screened, and infants born to HBsAg-positive women receive the first dose of vaccine and HBIg at birth; all other infants receive vaccine before hospital discharge;

  2. Universal vaccination: No screening, but all infants receive vaccine before hospital discharge; no infants receive HBIg; and

  3. Antiviral prophylaxis: All pregnant women are screened, and HBsAg-positive women have their HBV DNA load measured; antiviral prophylaxis is offered for 4 months starting in the third trimester to women with an HBV DNA load >106 copies/mL.[35]

The current US strategy for preventing perinatal HBV was considered to be cost-effective compared with the universal vaccination strategy. However, an antiviral prophylaxis strategy was considered to be cost saving, could prevent more HBV infections than the current strategy, and should be considered to continue to decrease the burden of perinatal HBV in the United States.


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