# HCC risk stratification scores: insights from large multi-center national cohort study

**Authors:** Imam Waked, Gamal Esmat, Mohamed Abdallah, Aisha Elsharkawy, Wafaa Elakel, Islam Ammar, Ehab Kamal, Mohamed Hassany, Nabiel Mikhail, Riham Soliman, Wahid Doss, Gamal Shiha

PMC · DOI: 10.1038/s41598-025-34535-w · 2026-02-03

## TL;DR

This study compares different risk scores for predicting liver cancer in patients who cleared hepatitis C, finding one score more effective for guiding surveillance.

## Contribution

The study identifies the GES score as the most accurate and clinically beneficial tool for HCC risk stratification in post-DAA patients.

## Key findings

- The GES score showed the highest AUC (0.632) and best calibration for predicting HCC risk.
- Decision curve analysis favored GES for its net clinical benefit in surveillance decisions.
- Implementation of GES could reduce healthcare burden by enabling individualized HCC surveillance.

## Abstract

Current guidelines advocate biannual HCC surveillance for chronic hepatitis C patients who achieved sustained virological response (SVR) following direct acting antivirals (DAAs), posing a heavy burden on healthcare systems. This study aimed to identify the most accurate and clinically useful risk stratification tool among patients who achieved SVR following DAAs in a large, multicenter national cohort. A retrospective study across 52 NCCVH centers in Egypt included 8,419 CHC patients with cirrhosis (F4) or advanced fibrosis (F3) who achieved SVR after DAAs and had complete follow-up data. Baseline data were used to calculate HCC risk scores (GES, aMAP, THRI, ALBI, FIB-4). Prognostic performance was assessed using Kaplan–Meier analysis, AUC, Harrell’s C-index, and Brier score with calibration plots. Decision curve analysis and Net Reclassification Improvement were applied to evaluate clinical utility and incremental prognostic value. All evaluated HCC risk scores showed adequate performance, with significant separation of incidence curves (log-rank p ≤ 0.05). GES demonstrated the highest AUC (0.632), followed by THRI (0.600) and aMAP (0.591), with C-indices around 0.63.Kaplan–Meier analysis confirmed significant survival differences between risk groups. GES had superior calibration (Brier score 0.197, slope 0.90). Decision Curve Analysis favored GES, offering the greatest net clinical benefit, especially at thresholds 0.1–0.3. NRI analysis showed aMAP worsened classification (NRI = − 0.16), while THRI offered minimal improvement over GES (NRI = + 0.05). Implementation of the GES score in Egypt’s national HCC surveillance program, enabling individualized surveillance and reducing healthcare burden in accordance with current EASL recommendations.

The online version contains supplementary material available at 10.1038/s41598-025-34535-w.

## Linked entities

- **Diseases:** HCC (MONDO:0007256), cirrhosis (MONDO:0005155)

## Full-text entities

- **Genes:** TLL1 (tolloid like 1) [NCBI Gene 7092] {aka ASD6, TLL}, AFP (alpha fetoprotein) [NCBI Gene 174] {aka AFPD, FETA, HPAFP}, GPC3 (glypican 3) [NCBI Gene 2719] {aka DGSX, GTR2-2, MXR7, OCI-5, SDYS, SGB}, ACE (angiotensin I converting enzyme) [NCBI Gene 1636] {aka ACE1, CD143, DCP, DCP1}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}
- **Diseases:** varices (MESH:D014648), chronic kidney diseases (MESH:D051436), hepatic lesions (MESH:D056486), dysplastic lesions (MESH:D004416), death (MESH:D003643), cardiac failure (MESH:D006333), Liver Disease (MESH:D008107), Viral Hepatitis (MESH:D014777), advanced (MESH:D020178), liver cirrhosis (MESH:D008103), GES (MESH:D000072861), malignancies (MESH:D009369), HCC (MESH:D006528), CHC (MESH:D019698), cirrhosis (MESH:D005355), splenomegaly (MESH:D013163), portal hypertension (MESH:D006975), HCV infection (MESH:D006526), infected (MESH:D007239)
- **Chemicals:** DAAs (-)
- **Species:** Homo sapiens (human, species) [taxon 9606], Hepatitis C virus [taxon 11103]

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12873163/full.md

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Source: https://tomesphere.com/paper/PMC12873163