Higher risk of postpartum phase transition to immune-active among HBeAg-positive pregnant women with indeterminate phase.

Background: Understanding the natural history of hepatitis B virus (HBV) infection helps determine the optimal timing of antiviral therapy. However, a gap exists in the literature regarding the dynamics of the natural history of HBV infection in pregnant women with chronic hepatitis B (CHB). This study aimed to explore the natural history of HBV infection during pregnancy and the postpartum period. Methods: We conducted a retrospective-prospective real-world study involving 276 pregnant women with CHB. Infection dynamics during pregnancy were characterized in 228 hepatitis B e-antigen (HBeAg)-positive and 48 HBeAg-negative participants, respectively, and during postpartum follow-up in 108 HBeAg-positive and 21 HBeAg-negative participants. HBeAg-positive participants received short-term antiviral intervention according to current guidelines. Liver disease progression was also evaluated. Results: Throughout pregnancy, the proportion of patients in the immune tolerance (IT) phase increased progressively, whereas the proportions of patients in the HBeAg-positive indeterminate phase (IP) and HBeAg-positive immune-active (IA) phase decreased. In the third trimester, the IT phase was dominant (48.7%), followed by the HBeAg-positive IP phase (24.6%), the HBeAg-positive IA phase (9.4%), the inactive carrier (IC) phase (9.4%), the HBeAg-negative IP phase (7.1%), and the HBeAg-negative IA phase (0.9%). During the postpartum period, a numerically higher cumulative incidence of phase maintenance (p = 0.150) and a significantly lower cumulative incidence of transition to the HBeAg-positive IA phase (p < 0.001) were observed in pregnant women in the IT phase compared with those in the HBeAg-negative IP phase. The cumulative incidence of phase maintenance (p = 0.900) and transition to the HBeAg-negative IA phase (p = 0.560) were comparable between pregnant women in the IC phase and those in the HBeAg-negative IP phase. The risk of postpartum liver disease progression was low among pregnant women across all disease phases. Conclusion: Pregnancy may have a pronounced impact on the dynamics of HBV infection in HBeAg-positive patients, particularly those in the IP phase at 24-28 weeks of gestation. Close postpartum monitoring is therefore warranted for this specific population. Clinical trial registration: https://www.clinicaltrials.gov, identifier ChiCTR2100054116.