Postpartum Hepatitis Flare Risk Increases After Discontinuation of Antiviral Therapy

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Findings from a recent study are highlighting the safety and efficacy of tenofovir disoproxil fumarate for preventing mother-to-child transmission of hepatitis B virus (HBV) in female patients with a high viral load during the second or third trimester of pregnancy.¹

Results published in Hepatology Research also call attention to an increased risk of hepatitis flares during the postpartum period after nucleos(t)ide analog discontinuation, with 5 out of 7 participants experiencing a flare within 6 months of stopping tenofovir disoproxil fumarate.¹

According to the World Health Organization, an estimated 254 million people were living with chronic HBV infection in 2022. In highly endemic areas, it is most commonly spread from mother to child at birth, with infection in infancy and early childhood leading to chronic infection in about 95% of cases. Although transmission can be prevented with antiviral medication, the risk of postpartum hepatitis flares after treatment discontinuation may pose a health risk to infected mothers.¹

“In particular, in cases where nucleos(t)ide analog administration is discontinued after delivery, hepatitis flares due to termination of HBV suppression are an important concern,” Hayato Kawamura, of the department of gastroenterology and metabolism at Nagoya City University Graduate School of Medical Sciences in Japan, and colleagues wrote.¹ “However, the association between antiviral therapy and hepatitis flares in women after the discontinuation of nucleos(t)ide analog for mother-to-child transmission prevention has not been elucidated.”

To examine the efficacy of nucleos(t)ide analog administration for the prevention of mother-to-child transmission of HBV and evaluate the risk of postpartum hepatitis flares after nucleos(t)ide analog discontinuation, investigators recruited pregnant women with HBV DNA ≥5.3 log IU/mL between September 2014 and March 2022 who received 300 mg tenofovir disoproxil fumarate orally once a day at approximately 28 weeks of gestation and discontinued treatment at 4–10 weeks after delivery. In total, investigators assessed the virological and biochemical parameters in 9 mothers after discontinuation, defining a hepatitis flare as an alanine transaminase (ALT) level ≥60 U/L.¹

HBeAg was positive in 8 cases with high levels of HBV DNA (7.7 to >8.2 log IU/mL), and negative in 1 case with 6.5logIU/mL of HBV DNA. The median time of tenofovir disoproxil fumarate initiation was 28 (interquartile range [IQR], 28–32) weeks of gestation. Tenofovir disoproxil fumarate was discontinued at 4 weeks postpartum in 6 cases, 5 weeks postpartum in 2 cases, and 10 weeks postpartum in 1 case.¹

Investigators noted a pair of cases were lost to follow-up after tenofovir disoproxil fumarate discontinuation. Of the remaining 7 patients, 5 experienced hepatitis flares within 6 months of tenofovir disoproxil fumarate discontinuation at a median of 11 (IQR, 9-17) weeks postpartum. Among these cases, the median peak ALT level was 165 (IQR, 108-262) U/L. In 3 of the 5 cases with hepatitis flares after treatment discontinuation, nucleos(t)ide analog was reintroduced.¹

Of note, none of the infants developed any congenital anomaly or acquired HBV infection during infancy. Accordingly, investigators suggested nucleos(t)ide analog administration appeared to be effective against mother-to-child transmission of HBV in pregnant women with high HBV DNA levels. However, they were also careful to outline potential limitations to these findings, including the limited number of cases included in the study and the fact that all included patients were treated with tenofovir disoproxil fumarate.¹

Nonetheless, they concluded that “the use of nucleos(t)ide analog in HBV-infected mothers with a high viral load during the second or third trimester of pregnancy was highly safe and effective against mother-to-child transmission. However, hepatitis flares were observed frequently in the postpartum period after nucleos(t)ide analog discontinuation.”

References:

1. ^{Kawamura H, Matsuura K, Ito K, et al. Efficacy of antiviral therapy for the prevention of mother-to-child transmission of hepatitis B virus and the risk of postpartum hepatitis flare after discontinuation of antiviral therapy. Hepatology Research. https://doi.org/10.1111/hepr.14048}
2. ^{World Health Organization. Hepatitis B. Newsroom. April 9, 2024. Accessed April 24, 2024. https://www.who.int/news-room/fact-sheets/detail/hepatitis-b}