Chronic hepatitis B (CHB) infection is a major global health problem with 296 million infected people worldwide resulting in 820,000 deaths annually (GlobalHealth/immunization/diseases/hepatitis-B, 2022). With high viral load and eAg positivity, mother-to-child transmission (MTCT) is a dominant risk factor for developing chronic hepatitis B virus (HBV) infection (Li et al., 2015, Boucheron et al., 2021). Tenofovir disoproxil fumarate (TDF), a nucleotide analogue works as an effective inhibitor of HBV polymerase and is a recommended antiviral treatment to prevent HBV MTCT (Pan et al., 2016). Recently, it was observed that TDF treatment from the second trimester achieved better viral suppression in highly viramic pregnant women without increasing adverse effects (Pan et al., 2016, Gao et al., 2019). Another study also revealed better safety and efficacy of TAF administered throughout or beginning of early pregnancy (Zeng et al., 2022).

In pregnancy, induction of Th2 immunity is well documented (Wang et al., 2020) which alters metabolic factors involved in generating an appropriate immune response to eradicate HBV infection (Jenkins et al., 2021). In chronic HBV infected pregnant women, immune responses are further impaired. Since, CD8+T cells are the main effector cells responsible for viral clearance, however, with increased Tregs and non-functional CD4+T cells and immature B cells their functionality is compromised (Vyas et al., 2019, Trehanpati et al., 2013, Shrivastava et al., 2013, Barili et al., 2021). NK cells play a key role in regulating HBV specific CD8+ T cells, and induce an innate mediated adaptive immune response. These effector immune cells produce an array of cytokines including IFN-γ and TNF-α responsible for HBV clearance (Schuch et al., 2014, Pierce, 2020, Cook, 2014). In addition, IFN-γ and IL-12 pro-inflammatory cytokines prevent immune tolerance and eradicate virus by balancing immune suppressive IL-10 and IL-15 anti-inflammatory cytokines (Zhong et al., 2021, Felices et al., 2018, Ryan and Frezza, 2021). MTCT and neonatal immunity direct reflection of maternal immune responses is compromised by high viral load, quantitative HBsAg and HBeAg positivity (Vyas et al., 2019). In addition to intricate maternal immune responses, fetal development and neonatal immunity are influenced by metabolic alterations (Yao et al., 2020, Armistead et al., 2020).

Successful pregnancies rely on adequate nutrient and energy supply for simultaneous metabolic adaptation in mother and fetus (Rees et al., 2022). Maternal metabolic changes during pregnancy readjust the immune homeostasis in obesity and viral infections (Rees et al., 2022). It was explicitly observed that in HBV infection, altered cellular metabolism helps in immune escape (Zhou et al., 2021). As integrated catabolic and anabolic pathways are vital for immune cells plasticity, however functional impact of specific metabolites to generate an effector immune response for viral decline remains unclear. Therefore, we aimed to understand how NA therapy during early pregnancy influences metabolic regulations and immunity during viral load decline and seroclearance.