Department of Biology of Systems, University of Alcalá, Alcalá de Henares, Spain.
Translational Research Group in Cellular Immunology, Instituto de Investigación Sanitaria de Castilla La-Mancha (IDISCAM), Toledo, Spain.
Front Immunol. 2024 Mar 13;15:1352929. doi: 10.3389/fimmu.2024.1352929. eCollection 2024.
HBe-antigen(Ag)-negative chronic hepatitis B virus (HBV) infection is characterized by little liver fibrosis progression and vigorous HBV-multispecific CD8 T-cell response.
To assess whether HBsAg level could discriminate different HBeAg-negative chronic HBV infection subtypes with dissimilar quality of HBV-specific CD8 T-cell response.
We recruited 63 HBeAg-negative chronic HBV infection patients in which indirect markers of liver inflammation/fibrosis, portal pressure, viral load (VL), and HBV-specific CD8 cell effector function were correlated with HBsAg level.
A positive linear trend between HBsAg level and APRI, liver stiffness (LS), liver transaminases, and HBV VL, and a negative correlation with platelet count were observed. Frequency of cases with HBV-specific CD8 T-cell proliferation against at least two HBV epitopes was higher in HBsAg < 1,000 IU/ml group. CD8 T-cell expansion after HBVpolymerase-specific stimulation was impaired in HBsAg > 1,000 IU/ml group, while the response against HBVcore was preserved and response against envelope was nearly abolished, regardless of HBsAg level. Cases with preserved HBVpolymerase CD8 cell response had lower LS/duration of infection and APRI/duration of infection rates. HBV-polymerase-specific CD8 T-cell proliferation intensity was negatively correlated with LS/years of infection ratio.
HBsAg > 1,000 IU/ml HBeAg-negative chronic HBV infection group shows indirect data of higher degree of inflammation, liver stiffness, and fibrosis progression speed, which are related to an impaired HBV-polymerase-specific CD8 T-cell response.
HBe 抗原（Ag）阴性慢性乙型肝炎病毒（HBV）感染的特征是肝纤维化进展较少和强烈的 HBV 多特异性 CD8 T 细胞反应。
评估 HBsAg 水平是否可以区分具有不同 HBV 特异性 CD8 T 细胞反应质量的不同 HBeAg 阴性慢性 HBV 感染亚型。
我们招募了 63 名 HBeAg 阴性慢性 HBV 感染患者，其中间接标志物肝炎症/纤维化、门静脉压力、病毒载量（VL）和 HBV 特异性 CD8 细胞效应功能与 HBsAg 水平相关。
HBsAg 水平与 APRI、肝硬度（LS）、肝转氨酶和 HBV VL 呈正线性趋势，与血小板计数呈负相关。HBsAg<1000IU/ml 组中至少有两种 HBV 表位的 HBV 特异性 CD8 T 细胞增殖的病例频率更高。HBsAg>1000IU/ml 组中 HBV 聚合酶特异性刺激后的 CD8 T 细胞扩增受损，而对 HBV 核心的反应得到保留，对包膜的反应几乎被消除，而与 HBsAg 水平无关。保留 HBV 聚合酶 CD8 细胞反应的病例具有较低的 LS/感染持续时间和 APRI/感染持续时间的比率。HBV 聚合酶特异性 CD8 T 细胞增殖强度与 LS/感染年限的比例呈负相关。
HBsAg>1000IU/ml 的 HBeAg 阴性慢性 HBV 感染组显示出更高程度的炎症、肝硬度和纤维化进展速度的间接数据，这与 HBV 聚合酶特异性 CD8 T 细胞反应受损有关。
