抗原引导的切换策略从细胞核到干扰素:避免病毒学突破并改善功能治疗
Da Huang1,2, Zhize Yuan1, Di Wu1,2
1Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Journal of medical virology
|November 12, 2024
概括
高基线水平的乙型肝炎核心相关抗原 (HBcrAg) 和HBsAg预测慢性乙型肝炎 (CHB) 患者的病毒学突破 (VBT),转换为基化干扰素α (Peg-IFN-α). 这些标志物表明免疫反应不佳,并阻碍功能治愈.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
背景情况:
- 慢性乙型肝炎 (CHB) 管理涉及顺序治疗,但从核胺类类似物 (NA) 转换为基化干扰素α (Peg-IFN-α) 后,预测病毒学突破 (VBT) 的因素仍然不清楚.
- 了解这些因素对于优化治疗策略和改善HBsAg损失等结果至关重要.
研究的目的:
- 在接受顺序Peg-IFN-α治疗方案的CHB患者中确定VBT的预测因子.
- 研究基线病毒标记物,免疫反应和治疗结果之间的关系,包括HBsAg损失和功能治愈.
主要方法:
- 对接受48周Peg-IFN-α加NA治疗的80名CHB患者的回顾性分析,随后接受48周Peg-IFN-α单疗法.
- 动态监测HBVDNA,HBsAg,HBcrAg,HBeAg,肝脏内ccDNA和免疫生物标志物 (CD8+ T细胞,Tfh,B细胞).
主要成果:
- 12名患者 (15.0%) 经历了VBT,治疗后HBsAg损失率显著降低 (0%vs35.3%).
- 基线升高的HBcrAg (≥5 log10 U/mL) 和HBsAg (≥100 IU/mL) 与最高的VBT风险和未能达到HBsAg清除有关.
- 患有高HBcrAg水平的患者具有更高的肝脏内ccDNA. 与风险较低的组相比,高HBcrAg/HBsAg组表现出免疫反应减弱 (CD8+ T细胞,Tfh,B细胞).
结论:
- 基线HBcrAg和HBsAg水平是VBT的显著预测指标,以及在CHB中对顺序Peg-IFN-α治疗的反应不佳.
- 监测这些病毒标志物可以帮助识别患有VBT风险的患者,并指导改善功能治愈率的策略.
- 低于最佳的免疫反应与高的HBcrAg和HBsAg水平相关,突出显示了病毒载量和宿主免疫力在治疗结果中的相互作用.
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