Abstract

Antiviral prophylaxis with tenofovir disoproxil fumarate (TDF) during pregnancy is the current standard of care to prevent mother-to-child transmission (MTCT) of chronic hepatitis B (CHB) infection in highly viremic mothers. We investigated the maternal and fetal outcomes in a large Chinese cohort of TDF-treated CHB pregnant subjects.

In this prospective study, consecutive treatment-naïve non-cirrhotic highly viremic (defined as hepatitis B virus [HBV] DNA ≥200,000 IU/mL) CHB mothers were treated with TDF at 24-28 weeks of pregnancy. In accordance with Chinese CHB guidelines, TDF was stopped right after delivery, or ≥4 weeks postpartum. Serum HBV DNA and alanine aminotransferase (ALT) were monitored every 6-8 weeks to determine virological relapse (VR, defined as HBV DNA ≥2 log increase from treatment cessation). Retreatment was indicated for VR + ALT above upper limit of normal. Infants were given HBV vaccine within 12 hours of birth, 1 and 6 months, in addition to HBV immunoglobulins. Serum hepatitis B surface antigen (HBsAg), antibody to HBV core (anti-HBc) and antibody to HBsAg (anti-HBs, lower limit of detection 10 IU/L) were checked in infants at 6 months.

A total of 330 eligible subjects were recruited (median age 30 [interquartile range IQR 28-32], 81.8% HBeAg+). At baseline, the median ALT was 17 (13-24) U/L and median HBV DNA was 7.82 (6.91-8.20) log IU/mL. At delivery, 6.2% remained highly viremic. TDF was stopped right after delivery in 66.4%, and ≥1 month in 33.6%. Among 293 with full follow-up data, VR was observed in 98.3% and 11.8% were retreated. Timing of TDF cessation, HBeAg status and DNA levels at delivery did not alter the risk of VR (Figure A) or retreatment (Figure B). Among 299 livebirths who had full serological profile at 6 months, 0% were HBsAg+, 23.1% were anti-HBc+, and 98.7% were anti-HBs+ (32.8% >1000 IU/L). On multivariate analysis, age (odds ratio [OR] 0.884, 95% CI 0.792-0.988), baseline ALT (OR 1.071, 95% CI 1.026-1.119), and infant anti-HBs >1000 IU/L (OR 0.364, 95% CI 0.133-0.996) were independently associated with retreatment. Infant anti-HBs >1000 IU/L (OR 7.203, 95% CI 3.913-13.200) and birth weight (OR 0.422, 95% CI 0.195-0.912) were independently associated with infant anti-HBc+.

Prophylactic TDF and neonatal immunization were highly effective to prevent MTCT of HBV in highly viremic mothers. Cessation of prophylactic TDF right after delivery showed similar rates of VR or retreatment compared to stopping TDF ≥4 weeks postpartum.

Figure legend:

Risk of A) VR and B) retreatment stratified by clinical parameters with respect to whether they were highly viremic at delivery, HBeAg status, and whether tenofovir was stopped at delivery vs stopped ≥4 weeks postpartum.