Ostankova Yulia V, Shchemelev Alexander N, Serikova Elena N, Kusevitskaya Marina B, Sannikov Maksim V, Gorskaya Olga A, Basina Valentina V, Shirshova Natalia Yu, Mashkov Ilya A, Zueva Elena B, Reingardt Diana E, Totolian Areg A
Saint Petersburg Pasteur Institute, 197101 St. Petersburg, Russia.
St. Petersburg State Institution of Health 'City Clinical Hospital No 31', 197110 St. Petersburg, Russia.
Int J Mol Sci. 2025 Sep 18;26(18):9079. doi: 10.3390/ijms26189079.
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.
乙型肝炎病毒（HBV）仍然是全球主要的健康问题，因为它不仅是最常见的嗜肝病毒之一，也是全球第七大死亡原因。最重要的感染途径包括垂直传播（出生前、期间或之后从母亲传给孩子，包括经胎盘感染）以及幼儿期通过与受感染父母的密切家庭接触进行的水平传播。我们研究的目的是评估俄罗斯圣彼得堡孕妇中慢性和隐匿性乙型肝炎病毒感染的患病率，包括分子特征分析。我们分析了1368名当地孕妇的血浆样本。HBV标志物的ELISA筛查包括定性检测HBsAg、抗-HBs IgG和抗-HBcore IgG。使用高灵敏度巢式PCR鉴定HBV DNA，随后对HBV DNA阳性病例进行全基因组测序。我们的研究评估了血清学和分子HBV标志物的患病率及其与年龄、疫苗接种状况和妊娠次数的关联。参与者中HBsAg、抗-HBs IgG和抗-HBcore IgG的血清学标志物检测率分别为1.9%、63.8%和12.9%。4.7%的孕妇检测到HBV DNA，其中2.8%为隐匿性HBV感染（OBI）。我们观察到抗-HBcore IgG与年龄呈正相关，但与抗-HBs IgG呈负相关；抗-HBcore IgG与疫苗接种状况呈负相关，而抗-HBs IgG呈正相关；HBsAg、抗-HBcore IgG和HBV DNA与妊娠次数呈正相关。我们还分析了具有临床意义的突变的患病率，包括耐药突变、逃逸突变（影响诊断检测和疫苗效力）以及与疾病进展相关的突变。HBsAg阴性HBV感染的检测与携带逃逸突变的循环病毒变体有关，这些变体在诊断检测中逃避HBsAg检测并逃避疫苗诱导抗体的中和作用。孕妇中携带双重威胁突变（那些通过HBsAg阴性导致诊断失败、降低疫苗/免疫球蛋白效力、病毒再激活、疾病进展）的HBV分离株占主导地位，这构成了重大的公共卫生风险，值得进一步研究。
