Systemic inflammatory dysregulation and short-term mortality in critically ill patients with sepsis and cirrhosis: incremental prognostic value of the aggregate index of systemic inflammation

Critically ill patients with sepsis and cirrhosis represent a high-risk population characterized by profound immune-inflammatory dysregulation, coagulation abnormalities, and poor short-term outcomes. The aggregate index of systemic inflammation (AISI), which integrates neutrophil, monocyte, lymphocyte, and platelet counts, may provide a comprehensive assessment of host inflammatory and immune status. However, its prognostic significance in this population remains unclear. This study evaluated the association of AISI with short-term mortality and its additional value for clinical risk stratification in critically ill patients with sepsis and cirrhosis. This retrospective multicohort study included critically ill patients with sepsis and cirrhosis from the MIMIC-IV database (development cohort) and the eICU Collaborative Research Database (independent replication cohort). The primary exposure was natural logarithm-transformed AISI (Ln AISI), analysed as both quartiles and continuously. The primary outcomes were 28-day and 90-day all-cause mortality. In eICU, outcomes were deaths recorded during hospitalisation within the respective follow-up windows; live discharges were censored at hospital discharge. Kaplan–Meier analysis, multivariable Cox proportional-hazards models, restricted cubic splines, propensity-score matching, and prediction analyses were used. A total of 822 patients from MIMIC-IV and 374 patients from eICU were included. Higher Ln AISI levels were associated with higher 28-day and 90-day mortality in both cohorts, with significant dose-response relationships across quartiles (all P for trend < 0.001). Kaplan-Meier analyses showed lower survival probabilities in higher Ln AISI quartiles. These associations remained directionally consistent after propensity score matching. Adding Ln AISI produced limited discrimination gains but improved risk-reclassification metrics and decision-curve net benefit. These findings indicate complementary prognostic information rather than evidence of immediate clinical utility. Elevated AISI was associated with increased short-term mortality in critically ill patients with sepsis and cirrhosis. AISI may provide complementary prognostic information when interpreted alongside established clinical predictors. Its incremental discrimination was limited, and prospective studies are needed before AISI can inform clinical decision-making.