COMMENTARY

New Strategies for Preventing Perinatal Transmission of Hepatitis B Virus

William F. Balistreri, MD

Disclosures

November 14, 2017

Logistical Questions

While the AASLD's guidelines support the use of third-trimester antiviral therapy for women at high risk for perinatal transmission, several areas remain unclear.[13,31]

What is the preferred antiviral drug? All of the three antiviral drug options have acceptable safety profiles. However, the majority of worldwide guidelines recommend tenofovir as the preferred choice for prevention of mother-to-child HBV transmission in view of the antiviral potency, more rapid viral decline with short-duration therapy, higher barrier to resistance, and available safety data during pregnancy compared with other antiviral agents.[13,30,31]

What is the HBV viral load threshold that warrants treatment? In a proposed algorithm for the management of HBsAg-positive mothers, 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.[13]

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.[12,13,36] What is not known is the potential for relapse if the drug is immediately discontinued after delivery. Hepatitis flares may occur in the postpartum period after antiviral therapy is discontinued; therefore, the mothers should be closely monitored for 6 months after treatment is stopped.[36,37,38,39,40,41] Carey and colleagues[40] reported that high HBV DNA levels during the second trimester of pregnancy were also predictive of postdelivery flares. The hepatitis flares are usually asymptomatic and resolve spontaneously.

Failure to Screen

If widely adopted, the practice of maternal antiviral administration could further reduce the global burden of chronic HBV infection, particularly in highly endemic countries.[13] This strategy requires that all pregnant women who are HBsAg positive have HBV DNA testing in the third trimester. Routine HBeAg screening and determination of viral load in expectant HBeAg-positive mothers could identify a subset of mother/infant pairs who are at higher risk for perinatal HBV transmission. However, HBV DNA screening is not consistently performed in the antenatal period. For example, one survey reported that only 80% of women had antenatal HBeAg testing, and 22% were HBeAg positive.[42,43]

Another issue is that HBV DNA levels are highly variable and unpredictable during pregnancy; thus, a previously healthy HBV carrier mother with a low HBV DNA level may become highly viremic during the last few weeks of pregnancy.[32]

Bottom Line

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. If widely adopted, this practice could further reduce the global burden of chronic HBV infection, particularly in highly endemic countries.[13]

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.[5,12,13,31] We will then be able to provide valid answers to the questions posed herein.

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