HES V2.0 Outperforms GALAD for Detection of HCC: A Phase 3 Biomarker Study in the United States

Authors

Hashem B El-Serag
Qingchun Jin
Nabihah Tayob
Emad Salem
Michelle Luster
Abeer Alsarraj
Saira Khaderi
Amit G Singal
Jorge A Marrero
Sumeet K Asrani
Fasiha Kanwal

Publication Date

2-1-2025

Journal

Hepatology

DOI

10.1097/HEP.0000000000000953

PMID

38899967

PMCID

PMC11655698

PubMedCentral® Posted Date

6-19-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Humans, Carcinoma, Hepatocellular, Liver Neoplasms, Male, Female, Middle Aged, Aged, alpha-Fetoproteins, Early Detection of Cancer, Biomarkers, Tumor, Prospective Studies, Retrospective Studies, United States, Alanine Transaminase, Prothrombin, Biomarkers, Protein Precursors

Abstract

BACKGROUND AND AIMS: The original hepatocellular carcinoma early detection screening (HES) score, which combines alpha-fetoprotein (AFP) with age, alanine aminotransferase, and platelets, has better performance than AFP alone for early HCC detection. We have developed HES V2.0 by adding AFP-L3 and des-gamma-carboxy prothrombin to the score and compared its performance to GALAD and ASAP scores among patients with cirrhosis.

APPROACH AND RESULTS: We conducted a prospective-specimen collection, retrospective-blinded-evaluation phase 3 biomarker cohort study in patients with cirrhosis enrolled in imaging and AFP surveillance. True-positive rate (TPR)/sensitivity and false-positive rate for any or early HCC were calculated for GALAD, ASAP, and HES V2.0 scores within 6, 12, and 24 months of HCC diagnosis. We calculated the AUROC curve and estimated TPR based on an optimal threshold at a fixed false-positive rate of 10%. We analyzed 2331 patients, of whom 125 developed HCC (71% in the early stages). For any HCC, HES V2.0 had higher TPR than GALAD overall (+7.2%), at 6 months (+3.6%), at 12 months (+7.2%), and 24 months (+13.0%) before HCC diagnosis. HES V2.0 had higher TPR than ASAP for all time points (+5.9% to +12.0%). For early HCC, HES V2.0 had higher sensitivity/TPR than GALAD overall (+6.7%), at 12 months (+6.3%), and 24 months (+14.6%) but not at 6 months (+0.0%) and higher than ASAP for all time points (+13.4% to +18.0%).

CONCLUSIONS: In a prospective cohort study, HES V2.0 had a significantly higher performance for identifying new HCC, including early stage, than GALAD or ASAP.