Stopping TDF prophylaxis immediately postpartum feasible in highly viraemic CHB mothers

In highly viraemic pregnant women with chronic hepatitis B (CHB), stopping peripartum prophylaxis (PP) with tenofovir disoproxil fumarate (TDF) immediately after delivery does not increase the risk of relapse or retreatment vs TDF cessation at ≥4 weeks postpartum. Early withdrawal of PP-TDF, combined with standard neonatal immunization schemes, is 100 percent effective in preventing mother-to-child transmission (MTCT).

“[These results suggest that] shortening the duration of PP-TDF from 12 weeks to [stopping] immediately after delivery can be considered,” noted the researchers from the University of Hong Kong (HKU). [JHEP Reports 2024;doi:10.1016/j.jhepr.2024.101050]

In the prospective study, 330 treatment-naïve noncirrhotic highly viraemic pregnant women with CHB (median age, 30 years; hepatitis B e antigen [HBeAg]–positive, 82.7 percent; median hepatitis B virus [HBV] DNA, 7.82 log IU/mL) were recruited from HKU–Shenzhen Hospital between July 2019 and June 2022. The participants were started on PP-TDF at 24–48 weeks of gestation (median, 26 weeks) to prevent MTCT. PP-TDF was continued throughout pregnancy and stopped either immediately after delivery (early withdrawal; n=213 [66.4 percent]) or ≥4 weeks after delivery (late withdrawal; n=108 [33.6 percent]), depending on the participants’ preference. Serum HBV DNA and alanine aminotransferase (ALT) were monitored every 6–8 weeks to determine virological relapse (primary endpoint).

In addition, all infants received standard neonatal hepatitis B immunization, including HBV vaccine within 12 hours of birth and at 1 month and 6 months, as well as hepatitis B immunoglobulin either immediately at birth (77.2 percent) or within 6 hours of birth (22.8 percent). Serum hepatitis B surface antigen (HBsAg), antibody to HBV core antigen (anti-HBc) and antibody to HBsAg (anti-HBs) were checked at 7–12 months of age.

Virological relapse, defined as HBV DNA >1 log increase following cessation of PP-TDF, was observed in 98.3 percent of participants. Rates of virological relapse did not differ significantly between the early and late withdrawal groups (99.0 percent vs 96.9 percent; p=0.338).

Clinical relapse, defined as virological relapse plus increase in ALT >2 times the upper limit of normal (ULN) at any time after PP-TDF cessation, also occurred at similar rates between the early and late withdrawal groups (19.5 percent vs 14.3 percent; p=0.332). Similar proportions of patients in the early vs late withdrawal group developed ALT flares 5 times ULN (2.1 percent vs 1.0 percent; p=0.464) and 10 times ULN (0.5 percent vs 0 percent; p=0.669).

Retreatment with TDF, recommended for participants with clinical relapse, was initiated at similar rates between the early and late withdrawal groups (12.3 percent vs 10.2 percent; p=0.573).

“Early withdrawal of PP-TDF, compared with late withdrawal, was not associated with risk of clinical relapse, degree of maximal ALT elevation, and retreatment,” the investigators pointed out.

Among 326 livebirths (male, 53 percent), no infants had HBsAg positivity at 6 months. Almost all infants (98.7 percent) developed seroconversion with anti-HBs >10 U/L, 50.5 percent had anti-HBs >100 U/L, and 32.8 percent showed strong vaccine response with anti-HBs >1,000 U/L. Nearly a quarter (23.1 percent) showed anti-HBc seropositivity.

“This study confirmed 100 percent effectiveness of the guideline-recommended strategy in preventing MTCT regardless of timing of TDF cessation, with high rate of vaccine response in infants,” the investigators concluded.