Tenofovir to Prevent Perinatal Transmission of Hepatitis B

Published - Written by Karen Sokal-Gutierrez, MD, MPH, FAAP

A 36-year-old pregnant woman, originally from Southeast Asia, presents to her family medicine physician for prenatal care in the first trimester. She has had no history of medical problems. On family history, she reports that her mother recently died of liver cancer due to hepatitis B virus (HBV). The patient’s prenatal screening indicates that she is hepatitis B e antigen (HBeAg)-positive, with normal liver function tests. The physician explains to the patient that the blood test showed that she is a chronic carrier of hepatitis B, which she likely got as a baby from her mother. The patient asks, “Are there any new treatments to prevent me from passing hepatitis B to my baby?”

Mother-to-child transmission of HBV is a leading cause of chronic HBV infection and liver cancer worldwide, particularly in Asia. Prior to the availability of perinatal interventions to prevent HBV transmission, mothers with chronic HBV infection had an approximate 1 in 3 chance of passing HBV to their baby during pregnancy, delivery, or infancy; and more than 65%-90% of infected children developed chronic HBV infection.

Over the past few decades, perinatal transmission of HBV has been reduced dramatically by two key interventions: Universal HBV immunization for infants starting at birth, with at least 3 doses by 6 months of age, and administration of hepatitis B immunoglobulin (HBIg) at birth to infants born to HBV-infected mothers. However, for mothers who are HBeAg-positive with high HBV loads (>200,000 IU/mL), perinatal HBV transmission still occurs in up to one third of cases. Researchers have postulated that perinatal administration of antiviral medication could inhibit HBV replication and reduce the risk of perinatal HBV transmission.

This week, NEJM published a multicenter, double-blind, randomized clinical trial conducted in Thailand to test the effectiveness of antiviral medication to prevent perinatal HBV transmission. A total of 331 HBeAg-positive pregnant women with normal liver function tests (ALT ≤60 IU/L) were randomized to receive tenofovir or placebo from 28 weeks of gestation to 2 months postpartum. All infants received HBIg at birth and HBV vaccine at birth and at ages 1, 2, 4, and 6 months. The primary outcome was HBV surface-antigen (HBsAg) positivity, confirmed by HBV-DNA in the infants at 6 months of age.

The results showed that maternal HBV viral load declined substantially in the tenofovir group, with no change in the placebo group; and at delivery, 12% of women in the tenofovir group had elevated HBV DNA levels versus 90% in the placebo group. Among the live-born babies, 0 of the 147 babies in the tenofovir group were HBsAg positive (0%; 95% CI, 0-2), compared to 3 of 147 in the placebo group (2%; 95% CI, 0-6), a nonsignificant difference (P=0.12). Adverse events in mothers and babies did not differ significantly between groups.

The authors concluded that in the setting of low HBV transmission rates, treating pregnant women with tenofovir in addition to administration of infant HBV vaccine and HBIg did not significantly reduce mother-to-child transmission of HBV. However, the small sample size may have limited the study’s ability to demonstrate statistical significance. This study joins a handful of similar studies — some considered low-quality — with conflicting results about whether antiviral treatment significantly reduces perinatal HBV transmission. As a result, expert recommendations have differed (e.g., the 2015 WHO hepatitis guidelines for management of chronic HBV did not recommend antiviral treatment, but the 2016 American Association for the Study of Liver Diseases guidelines did recommend antiviral treatment for pregnant women who were HBsAg positive with high HBV DNA levels). Dr. Lindsey Baden, an infectious diseases specialist and Deputy Editor at NEJM commented, “The benefits of preventing maternal-to-child transmission of HBV are life-long, and we must continue to improve our ability to do this. These data are encouraging, but it will require a substantially larger study to definitively demonstrate additional benefits to current practices.”

Returning to the physician and the pregnant patient, the physician should express sympathy about the patient’s mother’s death and reassure her that they will work closely together in consultation with a liver specialist to try to keep her healthy. The physician should also reassure the patient that the current treatments for babies born to women carrying hepatitis B, which were not available when she was born, can usually prevent hepatitis B from passing from mothers to babies. Because there a low risk of passing hepatitis B to the baby, the physician and patient should discuss whether the patient wishes to take tenofovir.

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Karen is a 2017-2018 NEJM Editorial Fellow, Clinical Professor at UC Berkeley-UCSF Joint Medical Program and UC Berkeley School of Public Health, researcher on children’s nutrition and oral health, and member of American Academy of Pediatrics.