Perinatal Transmission of the Hepatitis B Virus

Strategies for Prevention

William F. Balistreri, MD


June 04, 2015

In This Article

Remaining Questions

Guidance provided by the major liver societies support the use of third- trimester antiviral therapy for women at high risk for perinatal transmission; however, several areas of controversy remain, including the preferred antiviral drug, the HBV viral load threshold that warrants treatment, the gestational week at which to initiate therapy, and when to stop treatment after delivery.[4]

What is the preferred agent? Three oral antiviral drugs — lamivudine, telbivudine, and tenofovir — are available. All have acceptable safety profiles, but telbivudine and tenofovir are preferred over lamivudine, given the higher barrier to resistance and demonstrated safety in pregnancy.[2]

At what HBV DNA level should antiviral therapy be considered? Antiviral therapy should be considered when the maternal HBV DNA level is ≥ 107 copies/mL, and treatment should be started around week 28-32 of pregnancy to allow time for the virus to be suppressed.[2,4,62,63,64]

In a recent editorial, Sarkar and Terrault[4] proposed an algorithm for the management of HBsAg-positive mothers, focusing on the use of antiviral agents in pregnancy. They emphasize that the initial decision is whether the mother has active or advanced liver disease that requires the initiation or continuation of treatment during pregnancy, or if not, whether antiviral therapy in the third trimester is indicated to reduce the risk for perinatal transmission.

In another recent editorial, Hollinger[7] cautioned against making strict HBV DNA threshold recommendations for third- trimester therapy to prevent perinatal HBV transmission, given that published studies differ significantly in their recorded levels of protective efficacy. Prospective evaluation of any proposed algorithm or strategy is required to determine the efficacy and outcome.

When should the antiviral agent be discontinued? If therapy is administered primarily for prevention of mother-to-child transmission, it is suggested that the antiviral agent may be discontinued within the first 3 months after delivery.[1,4,15] What is not known is the potential for relapse if the drug is immediately discontinued after delivery.

The Bottom Line

The data summarized herein indicate that the provision of antiviral therapy during the third trimester to HBeAg-positive women is a safe and effective means of reducing mother-to-child transmission of HBV and that efficacy is highest if a viral load reduction to < 106 copies/mL is achieved.[4] This strategy requires clear stratification -- namely, that all pregnant women who are HBsAg-positive have HBV DNA testing in the third trimester to properly consider antiviral therapy. If widely adopted, this practice could further reduce the global burden of chronic HBV infection, particularly in highly endemic countries.

Substantial advances have been made globally in reducing perinatal HBV transmission, but this remains an ongoing health problem. Implementing existing policies on maternal screening and infant follow-up and addressing research gaps are needed to further reduce perinatal HBV transmission. A better understanding of the mechanisms of perinatal HBV transmission, including the functional impairments of newborn immunity, is also needed.[7]

Although highly promising, the best use of the proposed stratified strategy for antiviral treatment will emerge from studies that examine absolute risk reduction and determine the number needed to treat to prevent an unfavorable outcome.[7] We will then be able to provide valid answers to the questions posed in the clinical scenario posed at the beginning of this review.


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