Abstract / Summary
Abstract Infections are major drivers of decompensation and mortality in cirrhosis. High-density lipoprotein (HDL) and its major protein component apolipoprotein A-I (apoA-I) exhibit immune-modulatory properties, yet their role in predicting infection risk in cirrhosis remains poorly defined. This single-centre cohort study evaluated baseline HDL cholesterol (HDL-C) and apoA-I in 311 patients with cirrhosis (training: n = 225; temporal validation: n = 86). The primary endpoint was infection requiring antibiotic therapy within 12 months. Cox regression, C-indices and censoring-adjusted time-dependent ROC analyses assessed prognostic performance. Infections occurred in 24% of the training and 31% of the validation cohort. Lower HDL-C and apoA-I levels were significantly associated with infection risk in both cohorts. In the training cohort, both biomarkers improved discrimination when added to MELD. The biomarker models achieved higher C-indices and numerically higher 12-month AUCs than MELD and Child-Pugh alone. Discrimination attenuated in the validation cohort, where the biomarker-based models performed comparably to the established MELD and Child-Pugh scores. Training-derived exploratory cut-offs of HDL-C < 40.4 mg/dL and apoA-I < 98.5 mg/dL identified groups with higher infection risk. Occurrence of infection signaled a clear transition towards an unfavorable clinical trajectory, with a mortality rate of 41% during follow-up. These findings support HDL-C and apoA-I as candidate prognostic biomarkers of infection susceptibility. External validation and prospective assessment of clinical utility are needed; causal and therapeutic implications require dedicated investigation.