Concordance Index-Based Comparison of Inflammatory and Classical Prognostic Markers in Untreated Hepatocellular Carcinoma

<b>Background/Objectives</b>: Inflammation-based markers have emerged as potential prognostic tools in hepatocellular carcinoma (HCC), but comparative data with classical prognostic factors in untreated HCC are limited. This study aimed to evaluate and compare the prognostic performance of inflammatory and conventional markers using Harrell's concordance index (C-index). <b>Methods</b>: This retrospective study included 250 patients with untreated HCC. Prognostic variables included age, BCLC stage, Child-Pugh classification, Milan criteria, MELD score, AFP, albumin, Charlson comorbidity index, and the inflammation-based markers neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), Systemic Inflammation Response Index (SIRI), and Systemic Immune-inflammation Index (SIII). Survival was analyzed using Cox regression. Predictive performance was assessed using the C-index, Akaike Information Criterion (AIC), and likelihood ratio tests. <b>Results</b>: Among the classical markers, BCLC showed the highest predictive performance (C-index: 0.717), while NLR ranked highest among the inflammatory markers (C-index: 0.640), above the MELD score and Milan criteria. In multivariate analysis, NLR ≥ 2.3 remained an independent predictor of overall survival (HR: 1.787; 95% CI: 1.264-2.527; <i>p</i> < 0.001), along with BCLC stage, albumin, Charlson index, and Milan criteria. Including NLR in the model modestly improved the C-index (from 0.781 to 0.794) but significantly improved model fit (Δ-2LL = 10.75; <i>p</i> = 0.001; lower AIC). <b>Conclusions</b>: NLR is an accessible, cost-effective, and independent prognostic marker for overall survival in untreated HCC. It shows discriminative power comparable to or greater than most conventional predictors and may complement classical stratification tools for HCC.