Yan Wang, Jing Gu, Guanghua Chen, Yanfeng Jiang, Ying Xu, Xiaoping Huang, Wei Sun, Jianhe Gan
{"title":"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","authors":"Yan Wang, Jing Gu, Guanghua Chen, Yanfeng Jiang, Ying Xu, Xiaoping Huang, Wei Sun, Jianhe Gan","doi":"10.1186/s12985-025-02868-7","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusions: </strong>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.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":"22 1","pages":"281"},"PeriodicalIF":4.0000,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357373/pdf/","citationCount":"0","resultStr":"{\"title\":\"Roles of inflammatory cytokines in the pathogenesis of hepatitis B virus-related acute-on-chronic liver failure and CAR-T therapy.\",\"authors\":\"Yan Wang, Jing Gu, Guanghua Chen, Yanfeng Jiang, Ying Xu, Xiaoping Huang, Wei Sun, Jianhe Gan\",\"doi\":\"10.1186/s12985-025-02868-7\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusions: </strong>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.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>\",\"PeriodicalId\":23616,\"journal\":{\"name\":\"Virology Journal\",\"volume\":\"22 1\",\"pages\":\"281\"},\"PeriodicalIF\":4.0000,\"publicationDate\":\"2025-08-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357373/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Virology Journal\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s12985-025-02868-7\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"VIROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Virology Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12985-025-02868-7","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"VIROLOGY","Score":null,"Total":0}
Roles of inflammatory cytokines in the pathogenesis of hepatitis B virus-related acute-on-chronic liver failure and CAR-T therapy.
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.
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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