慢性乙型肝炎病毒感染者外周血免疫细胞和细胞因子的特征及免疫动态变化

Hepatitis B virus (HBV)-related immune injury-mediated local liver inflammation and hepatocyte death are critical for the progression of chronic hepatitis B (CHB). This cross-sectional study aimed to characterize the systematic variations of peripheral blood immune cells and the corresponding changes of cytokines/chemokines during CHB progression, without implying causal relationships. Peripheral blood immune cell subsets were detected by multiparametric flow cytometry, and the levels of cytokines/chemokines were measured using the Luminex discovery assay.

The study included CHB patients at different stages and healthy controls (HC), with data compared between groups, A multivariate analysis of variance (ANOVA) was used to adjust for potential confounding factors including age and gender. Compared with HC, initial CHB patients had a significantly higher frequency of total B cells (p < 0. 001) but a lower proportion of CD4 + T cells (p < 0. 01). The level of C-X-C chemokine ligand 10 (CXCL10) was markedly elevated in CHB patients (p < 0. 01) and positively correlated with B cell frequency.

Notably, CHB patients with serum Hepatitis B Surface Antigen (HBsAg) < 1500 ng/mL had higher CXCL10 levels than those with HBsAg ≥ 1500 ng/mL (p < 0. 05). In late-stage HBV infection (HBV-LC and HBV-HCC), the frequency of NK cells was significantly lower than that in CHB patients and healthy controls, while the frequency of T cells showed a relative increase.

Additionally, compared with CHB patients and HC, late-stage patients showed significantly higher levels of key cytokines/chemokines, including interferon-gamma (IFN-γ), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-C chemokine ligand 2 (CCL2), and tumor necrosis factor receptor I (TNFRI). This cross-sectional study reveals distinct alterations in peripheral blood immune cells and cytokines/chemokines across CHB progression, with CXCL10, NK cells, and multiple proinflammatory factors closely associated with disease stage and HBsAg levels.

These findings may provide potential biomarkers for monitoring CHB progression and theoretical support for immune-based therapeutic strategies, but causal relationships require verification by subsequent longitudinal studies.