Hepatitis B surface antigen (HBsAg) seroclearance is an optimal therapeutic endpoint, as it reflects the amount of covalently closed circular DNA. The exact mechanisms that contribute to HBsAg reduction are not completely understood. We evaluated adaptive immunity in nucleoside analog-experienced chronic hepatitis B (CHB) patients with low HBsAg levels who received oral antiviral therapy. One hundred and ninety-five CHB patients had hepatitis B virus (HBV) DNA ≤ 1000 IU/ml and HBsAg < 3000 IU/ml for longer than one year of antiviral therapy. According to HBsAg levels, they were divided into Group 1 (HBsAg reduction ≥ 0.5 log₁₀) and Group 2 (HBsAg reduction < 0.5 log₁₀). Cytokines, adaptive immune cells, and molecular markers in peripheral blood were detected at follow-up times. In total, 38 (19.5%) of the 195 patients achieved HBsAg reduction ≥ 0.5 log₁₀. IL4, IL5, IL10, TGF β, IL17, and PD-1 decreased gradually in these patients. HBsAg reduction had a link to the change in ICOSL⁺CD19⁺ B cells and CD40L⁺CXCR5⁺CD4⁺ Tfh cells. More CD8⁺ naive T lymphocytes differentiated into CD4⁺ T_CMs, CD8⁺ T_CMs and CD8⁺ T_EMs in Group 1. Meanwhile, Group 1 exhibited elevated Th1 and Th1/Th2 levels and reduced levels of Treg versus those in Group 2. With the reduction in HBsAg, the imbalance of T-cell subsets was partially corrected; the immune activity of T cells was enhanced, and the state of immune exhaustion was alleviated to a certain extent.

乙型肝炎表面抗原 (HBsAg) 血清清除是最佳治疗终点，因为它反映了共价闭合环状 DNA 的数量。有助于减少 HBsAg 的确切机制尚不完全清楚。我们评估了接受口服抗病毒治疗的低 HBsAg 水平的核苷类似物慢性乙型肝炎 (CHB) 患者的适应性免疫。195 名 CHB 患者的乙型肝炎病毒 (HBV) DNA ≤ 1000 IU/ml 且 HBsAg < 3000 IU/ml 抗病毒治疗超过一年。根据HBsAg水平，分为第1组（HBsAg降低≥0.5 log ₁₀）和第2组（HBsAg降低<0.5 log _{10 ）}). 随访期间检测外周血中的细胞因子、适应性免疫细胞和分子标志物。总共 195 名患者中有 38 名 (19.5%) 的 HBsAg 降低 ≥ 0.5 log ₁₀。这些患者的 IL4、IL5、IL10、TGF β、IL17 和 PD-1 逐渐降低。^{HBsAg 减少与 ICOSL +} CD19 ⁺ B 细胞和 CD40L ⁺ CXCR5 ⁺ CD4 ⁺ Tfh 细胞的变化有关。更多 CD8 ⁺幼稚 T 淋巴细胞分化为 CD4 ⁺ T _CM、CD8 ⁺ T _CM和 CD8 ⁺ T _EM在第 1 组中。同时，与第 2 组相比，第 1 组表现出升高的 Th1 和 Th1/Th2 水平以及降低的 Treg 水平。随着 HBsAg 的减少，T 细胞亚群的失衡得到部分纠正；T细胞免疫活性增强，免疫衰竭状态得到一定程度的缓解。