Association between HALP score and in-hospital mortality in sepsis patients: a multicenter retrospective cohort study with external validation

Background The HALP (Hemoglobin, Albumin, Lymphocyte, and Platelet) score integrates key parameters reflecting nutritional and immune status. However, its prognostic value for in-hospital mortality in sepsis patients remains underexplored. Objective To investigate the association between HALP score and in-hospital mortality in sepsis patients using two large critical care databases. Methods We conducted a retrospective cohort study including adult patients with Sepsis-3 from the eICU Collaborative Research Database (derivation cohort, n = 12,899) and the MIMIC-IV database (validation cohort, n = 3,726). HALP was calculated as (hemoglobin × albumin × lymphocyte count)/platelet count, using first available values upon ICU admission. Restricted cubic spline (RCS) models assessed nonlinear relationships between HALP and mortality. Kaplan–Meier survival curves and multivariable Cox regression models, adjusted for demographics, comorbidities, laboratory values, and Acute Physiology Score III, evaluated survival differences between low- and high-HALP groups. Segmented Cox regression examined associations below and above RCS-derived thresholds. Results A total of 16,625 patients were analyzed. RCS analysis demonstrated significant nonlinear associations between HALP and in-hospital mortality in both cohorts (overall P < 0.001; nonlinearity P < 0.001 in eICU, P = 0.002 in MIMIC-IV), with an inflection point near 12.45. Below this threshold, each unit increase in HALP was associated with a 3% reduction in mortality risk (eICU: HR 0.97, 95% CI 0.95–0.99, P = 0.002; MIMIC-IV: HR 0.97, 95% CI 0.94–0.99, P = 0.008). Kaplan–Meier analyses showed significantly higher survival in the high HALP group (eICU: log-rank P = 0.005, HR 0.882, 95% CI 0.808–0.962; MIMIC-IV: log-rank P < 0.001, HR 0.723, 95% CI 0.607–0.862). Multivariable Cox regression confirmed that high HALP remained independently protective after full adjustment (eICU: HR 0.90, 95% CI 0.82–0.98, P = 0.017; MIMIC-IV: HR 0.85, 95% CI 0.74–0.98, P = 0.028). Conclusion The HALP score demonstrates robust prognostic value for predicting in-hospital mortality in sepsis patients, with consistent nonlinear relationships validated across two large databases. Its simplicity and reliance on routine laboratory parameters support potential clinical application in sepsis risk stratification.