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

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. 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. 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). 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. Not applicable.