Roles of inflammatory cytokines in the pathogenesis of hepatitis B virus-related acute-on-chronic liver failure and CAR-T therapy.

IF 4 3区 医学 Q2 VIROLOGY
Yan Wang, Jing Gu, Guanghua Chen, Yanfeng Jiang, Ying Xu, Xiaoping Huang, Wei Sun, Jianhe Gan
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引用次数: 0

Abstract

Objective: To investigate the association between inflammatory cytokines and liver function indices in hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) patients and chimeric antigen receptor (CAR) T therapy recipients, with the aim of identifying prognostic biomarkers and elucidating the pathophysiological roles of inflammatory cytokines in HBV-ACLF.

Methods: This retrospective cohort study analyzed clinical data from three groups: 68 patients with confirmed HBV-ACLF, 30 patients with pre-HBV-ACLF, and 372 hematologic malignancy patients receiving CAR-T therapy with preserved liver function at the First Affiliated Hospital of Soochow University.

Results: Serum interleukin (IL)-10 levels demonstrated a progressive increase across the groups [healthy controls: 0.15 (0.10;2.18) pg/mL; pre-HBV-ACLF: 3.80 (2.38;11.83) pg/mL; HBV-ACLF: 5.95 (3.90;14.75) pg/mL; p < 0.001]. Patients with clinical improvement exhibited significantly lower IL-10 concentrations and higher IL-6/IL-10 ratios compared to those with disease progression (p < 0.05). Notably, IL-6 levels remained stable across clinical stages, with HBV-ACLF patients without secondary infection showing lower IL-6 levels than pre-HBV-ACLF patients (p < 0.05). Following CAR-T therapy, hematologic patients displayed significantly elevated IL-6 levels, accompanied by increases in AST and INR prolongation, whereas TBIL and ALT remained stable (p > 0.05). Consistent with HBV-ACLF observations, improved CAR-T recipients demonstrated significantly lower IL-6/IL-10 ratios than progression patients (p < 0.05).

Conclusions: IL-10 exhibits stage-dependent dynamics in HBV-ACLF pathogenesis and progression, closely mirroring hepatic functional deterioration. The IL-6/IL-10 ratio serves as a prognostic biomarker for both HBV-ACLF and CAR-T therapy-related liver injury, with lower ratios indicating better clinical outcomes.

Clinical trial number: Not applicable.

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炎症细胞因子在乙型肝炎病毒相关的急性慢性肝衰竭发病机制和CAR-T治疗中的作用
目的:探讨炎症因子与乙肝病毒相关急性-慢性肝衰竭(HBV-ACLF)患者和CAR - T治疗患者肝功能指标的关系,以确定预后生物标志物,阐明炎症因子在HBV-ACLF中的病理生理作用。方法:本回顾性队列研究分析了三组临床资料:68例确诊HBV-ACLF患者、30例HBV-ACLF前患者和372例接受CAR-T治疗并保留肝功能的血液恶性肿瘤患者。结果:血清白细胞介素(IL)-10水平在各组间呈渐进式升高[健康对照组:0.15 (0.10;2.18)pg/mL;前hbv - aclf: 3.80 (2.38;11.83) pg/mL;HBV-ACLF: 5.95 (3.90;14.75) pg/mL;p 0.05)。与HBV-ACLF观察结果一致,改良CAR-T受体的IL-6/IL-10比值明显低于进展患者(p结论:IL-10在HBV-ACLF发病和进展中表现出阶段依赖的动态,密切反映肝功能恶化。IL-6/IL-10比值是HBV-ACLF和CAR-T治疗相关肝损伤的预后生物标志物,比值越低表明临床结果越好。临床试验号:不适用。
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来源期刊
Virology Journal
Virology Journal 医学-病毒学
CiteScore
7.40
自引率
2.10%
发文量
186
审稿时长
1 months
期刊介绍: Virology Journal is an open access, peer reviewed journal that considers articles on all aspects of virology, including research on the viruses of animals, plants and microbes. The journal welcomes basic research as well as pre-clinical and clinical studies of novel diagnostic tools, vaccines and anti-viral therapies. The Editorial policy of Virology Journal is to publish all research which is assessed by peer reviewers to be a coherent and sound addition to the scientific literature, and puts less emphasis on interest levels or perceived impact.
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