Abstract: Hepatitis B virus (HBV) remains a major global health concern, as it is not only one of the most common hepatotropic viruses but also ranks as the seventh leading cause of mortality worldwide. The most significant routes of infection include vertical transmission (from mother to child before, during, or after birth, including transplacental infection) and horizontal transmission in early childhood through close household contact with infected parents. The aim of our study was to assess the prevalence of chronic and occult hepatitis B virus infection among pregnant women in St. Petersburg (Russia), including molecular characterization. We analyzed plasma samples from 1368 local pregnant women. ELISA screening for HBV markers included qualitative detection of HBsAg, anti-HBs IgG, and anti-HBcore IgG. HBV DNA was identified using highly sensitive nested PCR, followed by whole-genome sequencing for HBV DNA-positive cases. Our study evaluated the prevalence of serological and molecular HBV markers and their association with age, vaccination status, and number of pregnancies. Serological markers HBsAg, anti-HBs IgG, and anti-HBcore IgG were detected in 1.9%, 63.8%, and 12.9% of participants, respectively. HBV DNA was found in 4.7% of pregnant women, including 2.8% with occult HBV infection (OBI). We observed a positive correlation between anti-HBcore IgG and age, but an inverse correlation with anti-HBs IgG; an inverse correlation between anti-HBcore IgG and vaccination status, while anti-HBs IgG showed a positive correlation; and a positive correlation between HBsAg, anti-HBcore IgG, and HBV DNA with the number of pregnancies. We also analyzed the prevalence of clinically significant mutations, including drug resistance mutations, escape mutations (affecting diagnostic detection and vaccine efficacy), and mutations associated with disease progression. The detection of HBsAg-negative HBV infection was linked to circulating viral variants carrying escape mutations, which evade HBsAg detection in diagnostic assays and neutralization by vaccine-induced antibodies. The predominance of HBV isolates in pregnant women harboring dual-threat mutations (those causing diagnostic failure via HBsAg negativity, reduced vaccine/immunoglobulin efficacy, viral reactivation, disease progression) poses a significant public health risk and warrants further investigation.
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