Systemic immune-inflammatory disturbance and multiorgan dysfunction in patients with sepsis-associated...

This study aimed to investigate the clinical features of immune-inflammatory disturbance and clarify their correlations with multiorgan dysfunction and 28-day mortality in patients with sepsis-associated acute-on-chronic liver failure (ACLF).

We retrospectively enrolled 116 patients with sepsis-associated ACLF (January 2021-December 2025), divided by 28-day prognosis into survivor (n=48) and non-survivor (n=68) groups. Baseline data within 24 hours of admission, including severity scores [sequential organ failure assessment (SOFA), chronic liver failure consortium ACLF score (CLIF-C ACLF), model for end-stage liver disease (MELD), albumin-bilirubin score (ALBI)], serum inflammatory cytokines [interleukin-6 (IL-6), interleukin-18 (IL-18), interleukin-10 (IL-10), procalcitonin (PCT), etc.], cellular immune markers [CD4⁺/CD8⁺ ratio, human leukocyte antigen-DR (HLA-DR), neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SIRI), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR)], and organ function indices, were collected and compared between groups. Correlations between immune-inflammatory markers and multiorgan dysfunction were analyzed using Spearman correlation.

The 28-day mortality was 58.62% (68/116). Non-survivors had significantly higher severity scores (all P<0.001), elevated pro-inflammatory cytokines IL-6, IL-18, and PCT (P<0.05), lower IL-10 (P=0.004), and reduced CD4⁺ T cells, CD4⁺/CD8⁺ ratio, and HLA-DR expression (all P<0.001). Composite inflammatory indices (NLR, SIRI, PLR) were significantly elevated and LMR decreased in non-survivors (all P<0.001). Non-survivors also exhibited worse organ function and significantly higher incidences of acute kidney injury, acute respiratory distress syndrome, hepatic encephalopathy, and circulatory failure (all P<0.05). Spearman analysis showed that IL-6, NLR, SIRI, and PLR were positively correlated with the number of organ dysfunctions, while CD4⁺/CD8⁺ ratio and LMR were negatively correlated (all P<0.05).

Sepsis-associated ACLF presents with systemic immune-inflammatory disturbance characterized by concurrent pro-inflammatory cytokine storm and immunoparalysis. Dynamic monitoring of immune-inflammatory biomarkers may facilitate early risk stratification and provide a basis for immune-guided stratified therapy.