Spotlight on perinatal HBV

A double-blind trial compared the effectiveness of tenofovir disoproxil fumarate versus placebo for prevention of perinatal transmission of hepatitis B virus (HBV), while another study examined postpartum disease flares of treatment-naïve mothers with chronic HBV.

Two recent studies assessed cohorts of pregnant and postpartum women with chronic hepatitis B virus (HBV).

In one double-blind trial conducted in 17 hospitals in Thailand, researchers compared the effectiveness of tenofovir disoproxil fumarate versus placebo in preventing pregnant women's transmission of HBV infection to their infants. They randomized 331 hepatitis B e antigen-positive pregnant women to receive tenofovir disoproxil fumarate (n=168) or placebo (n=163) from 28 weeks of gestation to two months postpartum. Infants received hepatitis B immune globulin at birth, as well as HBV vaccine at birth and at ages one, two, four, and six months.

The primary end point was hepatitis B surface antigen (HBsAg)-positive status in the infant, confirmed by the level of HBV DNA at age 6 months. Results were published online on March 8 by the New England Journal of Medicine.

Among 322 deliveries (319 singleton births, two pairs of twins, one stillborn), there were no significant differences between groups. In the tenofovir disoproxil fumarate group, 0 of 147 infants (0%; 95% CI, 0% to 2%) were infected, compared to 3 of 147 (2%; 95% CI, 0% to 6%) in the placebo group (P=0.12). The study authors noted that the strict HBV immunization schedule may have contributed to the low rate of transmission.

“Although this trial and other studies point to some value for antiviral prophylaxis in preventing mother-to-child transmission, this trial did not prove the superiority of [tenofovir disoproxil fumarate] prophylaxis,” an accompanying editorial stated. “The low rate of transmission in the placebo group … implies a role for the administration of the HBV vaccine within hours after birth to reduce the risk of mother-to-child transmission without additional testing or antiviral therapy in mothers with high levels of viremia.”

A second study, published online on Feb. 27 by the American Journal of Gastroenterology, characterized postpartum disease flares of treatment-naïve mothers with chronic HBV. Researchers enrolled a group of 3,367 infected mothers and compared them to a group of 869 noninfected mothers in terms of postpartum alanine aminotransferase (ALT) abnormalities.

Elevated ALT and detectable HBV DNA levels at delivery were independent predictors of both flares and exacerbations. Infected mothers had a higher frequency of abnormal ALT levels than noninfected mothers (28.27% vs. 20.37%, P<0.001), and ALT levels peaked at postpartum weeks 3 to 4 and 9 to 12.

Among infected mothers, 1,928 had detectable serum levels of HBV DNA, and these women had a greater frequency of ALT events compared to others (flares, 115 of 1,928 [5.96%]; exacerbations, 57 of 1,928 [2.96%]). In a subgroup analysis, a cutoff HBV DNA level of 5 log10 IU/mL at delivery or greater predicted postpartum ALT events (positive predictive value, 14.4%; negative predictive value, 98.2%).

The study authors noted that limitations of the study include its retrospective design and the relatively small number of patients in the control group.