Prognostic Value of the Endothelial Activation and Stress Index for Short- and Mid-Term Mortality in Critically Ill Patients With Cirrhosis

Background: Critically ill patients with cirrhosis experience high short- and long-term mortality, with substantial heterogeneity in clinical outcomes. Endothelial dysfunction plays a central role in systemic decompensation and multiorgan failure in advanced cirrhosis. The Endothelial Activation and Stress Index (EASIX) is a simple biomarker reflecting endothelial injury, but its prognostic value in critically ill cirrhotic patients remains unclear. Methods: We conducted a retrospective cohort study of 3,797 critically ill patients with cirrhosis. EASIX values were natural logarithm–transformed (lnEASIX) to account for skewed distributions and subsequently categorized according to the median value (1.35). Patients were classified into low (≤1.35) and high (>1.35) lnEASIX groups. The primary endpoints were in-hospital all-cause mortality and all-cause mortality at 1 year and 2 years following hospital discharge. Associations between lnEASIX and outcomes were assessed using multivariable regression models, Kaplan–Meier survival analyses, restricted cubic spline (RCS) modeling, and receiver operating characteristic (ROC) curve analyses. Results: Mortality rates were consistently higher among patients with elevated lnEASIX across all evaluated time points. After comprehensive adjustment for demographic characteristics, clinical variables, comorbidities, and laboratory parameters, high lnEASIX remained independently associated with increased risks of in-hospital mortality (hazard ratio [HR] 1.99, 95% confidence interval [CI] 1.59–2.49), 1-year mortality (HR 1.28, 95% CI 1.05–1.55), and 2-year mortality (HR 1.33, 95% CI 1.10–1.60). RCS analyses demonstrated a linear relationship between lnEASIX and mortality risk without evidence of non-linearity. lnEASIX exhibited strong discriminative performance for in-hospital mortality (area under the curve [AUC] 0.871, 95% CI 0.857–0.885) and moderate predictive ability for post-discharge mortality. Subgroup analyses revealed effect modification by sex and the presence of hepatorenal syndrome. Conclusions: In critically ill patients with cirrhosis, EASIX is independently associated with short- and mid-term mortality. As a simple marker capturing systemic endothelial activation and stress, EASIX may provide complementary prognostic information beyond conventional scoring systems and support early risk stratification in this high-risk population.