At Delivery? 4 Weeks Later? When Is the Best Time to Discontinue HBV Prophylaxis Therapy Postpartum?

The WHO estimates that more than 250 million people are living with chronic hepatitis B virus (HBV) infection worldwide, and that the majority of HBV-associated deaths are due to mother-to-child transmission (MTCT) or infection within the first 5 years of life. Growing evidence on the efficacy and safety of antiviral prophylaxis in pregnant women with HBV to decrease MTCT has led to recommendations that, in women without standard HBV therapy indications but with HBV DNA >200,000 IU/mL, we should consider nucleotide analogue therapy from the third trimester. It is important to identify pregnant women who meet standard treatment indications independently of MTCT considerations, as treatment duration would not be limited to the peripartum period.

When to Discontinue MTCT Prophylaxis
Although prophylaxis indications (HBV DNA >200,000 IU/mL), timing of initiation (at 28 weeks), and agent of choice (tenofovir) are widely accepted, there remains uncertainty on the optimal timing for prophylaxis discontinuation postpartum.

The concern regarding prophylaxis discontinuation revolves around the risk of HBV flare, with elevation in alanine aminotransferase (ALT) and HBV DNA, that holds the menace of the feared but very rare complication of acute liver failure. To provide context to this concern, it is important to remember that postpartum HBV flares happen frequently (up to 30%-50%) in women with HBV who are not on antiviral prophylaxis. They usually occur around Weeks 4 and 12, typically are not severe, and can be monitored for the most common result—spontaneous resolution. These flares can be associated with the favorable clinical outcome of HBV seroconversion and, furthermore, can be managed with antiviral therapy with favorable clinical response.

Current Guidance
Women who receive third-trimester prophylaxis have been reported to have ALT elevation similar to untreated women (up to 45% of women) with rare reports of severe flares of ALT >5-10 times the upper limit of normal. Based on these studies, the American Association for the Study of Liver Diseases has suggested discontinuation at delivery or up to 4 weeks postpartum, whereas the European Association for the Study of the Liver has suggested discontinuation up to 12 weeks postpartum. However, a recent study suggested that prophylaxis discontinuation at delivery or 6 weeks postpartum was associated with no differences in rates of ALT elevation (around 50%) or ALT peak (mild ~100 IU/L) when compared to no prophylaxis.

My Approach
My approach to caring for pregnant women with HBV is to engage them by providing information about the possible benefits of prophylaxis to prevent MTCT with antivirals as well as the standard HBV vaccination and hepatitis B immunoglobulin for the infant. In addition, I emphasize that HBV is a condition that will require lifelong monitoring and care and that will require follow-up beyond the peripartum and postpartum periods. I review the risks of HBV flare and the need for monitoring of ALT and HBV DNA to allow recognition of the flare and to identify potential progression of the patient to meeting standard HBV treatment indications.

My practice is to discontinue antiviral prophylaxis at delivery and monitor ALT and HBV DNA at Weeks 6 and 12 postpartum, before returning to every-6-month monitoring. If an ALT elevation is detected, in the absence of symptoms, jaundice, coagulopathy, or features of hepatic encephalopathy, watchful clinical monitoring is followed with the recognition and reassurance that most elevations are self-limited or respond to reinitiation of antiviral therapy.

Engagement of the patient in her own health, supporting agency in decision making, and providing continuity of care can help break the chain of HBV MTCT and optimize the health of both the patient and her children.

Your Thoughts?
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