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

**Authors:** Natalia Afonso-Luis, Irene Monescillo-Martín, Joaquín Marchena-Gómez, Pau Plá-Sánchez, Francisco Cruz-Benavides, Carmen Rosa Hernández-Socorro

PMC · DOI: 10.3390/jcm14155514 · 2025-08-05

## TL;DR

This study compares the usefulness of inflammation-based and traditional markers in predicting survival in untreated liver cancer patients.

## Contribution

The study introduces a comparison of inflammatory markers like NLR with classical HCC prognostic tools using the C-index.

## Key findings

- BCLC stage had the highest predictive performance (C-index: 0.717) among classical markers.
- NLR was the top-performing inflammatory marker (C-index: 0.640) and an independent predictor of survival.
- Adding NLR to the model improved model fit and slightly increased the C-index.

## Abstract

Background/Objectives: 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). Methods: 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. Results: 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; p < 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; p = 0.001; lower AIC). Conclusions: 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.

## Linked entities

- **Diseases:** hepatocellular carcinoma (MONDO:0007256), HCC (MONDO:0007256)

## Full-text entities

- **Genes:** AFP (alpha fetoprotein) [NCBI Gene 174] {aka AFPD, FETA, HPAFP}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}
- **Diseases:** HCC (MESH:D006528), Inflammation (MESH:D007249)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12347834/full.md

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Source: https://tomesphere.com/paper/PMC12347834