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Clinical Trial
. 2025 Feb;168(2):316-326.e6.
doi: 10.1053/j.gastro.2024.09.008. Epub 2024 Sep 16.

A Phase 3 Biomarker Validation of GALAD for the Detection of Hepatocellular Carcinoma in Cirrhosis

Tracey L Marsh  1 , Neehar D Parikh  2 , Lewis R Roberts  3 , Myron E Schwartz  4 , Mindie H Nguyen  5 , Alex Befeler  6 , Stephanie Page-Lester  1 , Nabihah Tayob  7 , Sudhir Srivastava  8 , Jo Ann Rinaudo  8 , Amit G Singal  9 , K Rajender Reddy  10 , Jorge A Marrero  11
Affiliations
Clinical Trial

A Phase 3 Biomarker Validation of GALAD for the Detection of Hepatocellular Carcinoma in Cirrhosis

Tracey L Marsh et al. Gastroenterology. 2025 Feb.

Abstract

Background & aims: Better surveillance tests for hepatocellular carcinoma (HCC) are needed. The GALAD score (gender, age, α-fetoprotein [AFP] L3, AFP, and des-γ carboxyprothrombin) has been shown to have excellent sensitivity and specificity for HCC in phase 2 studies. We performed a phase 3 biomarker validation study to compare GALAD with AFP in detecting HCC.

Methods: This is a prospective study of patients with cirrhosis enrolled at 7 centers. Surveillance for HCC was performed every 6 months at each site, and HCC diagnosis was confirmed per American Association for the Study of Liver Diseases guidelines. Blood for biomarker research was obtained at each follow-up visit and stored in a biorepository. Measurements of AFP, AFP-L3, and des-γ carboxyprothrombin) were performed in a FujiFilm laboratory by staff blinded to clinical data. The performance of GALAD in detecting HCC was retrospectively evaluated within 12 months before the clinical diagnosis. All analyses were conducted by an unblinded statistician in the Early Detection Research Network data management and coordinating center.

Results: A total of 1,558 patients with cirrhosis were enrolled and followed for a median of 2.2 years. A total of 109 patients developed HCC (76 very early or early stage), with an annual incident rate of 2.4%. The areas under the curve for AFP and GALAD within 12 months before HCC were 0.66 and 0.78 (P < .001), respectively. Using a cutoff for GALAD of -1.36, the specificity was 82%, and the sensitivity at 12 months before HCC diagnosis was 62%. For comparison, performance of AFP at 82% specificity showed 41% sensitivity at 12 months before HCC diagnosis (P = .001).

Conclusions: GALAD score, compared to AFP, improves the detection of HCC within 12 months before the actual diagnosis.

Keywords: AFP; Early Detection; GALAD; Hepatocellular Carcinoma.

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Conflict of interest statement

These authors disclose the following: Tracey L. Marsh has no conflicts to disclose.Neehar D. Parikh is a consultant for Exact Sciences, Eli Lilly, and Freenome; has served on advisory boards of Genentech, Eisai, Bayer, Exelixis, Gilead, Wako/Fujifilm; and has received research funding from Bayer, Target RWE, Exact Sciences, Genentech and Glycotest. Lewis R. Roberts is a consultant for Glycotest. Mindie H. Nguyen has consulted and/or served on the advisory board for Intercept, Exact Science, Gilead, GSK, Exelixis; and has received research support (to Stanford University) from Pfizer, Enanta, Astra Zeneca, GSK, Delfi, Innogen, Exact Science, CurveBio, Gilead, Vir Biotech, Helio Health, Glycotest, B.K. Kee Foundation. Alex Befeler has served on the speaker’s bureau for Mallinckrodt; and has received research support (paid to Saint Louis University) from Exact Sciences. Amit G. Singal is a consultant with Bayer, FujiFilm Medical Sciences, Exact Sciences, Universal Dx, Glycotest, Roche, Freenome, GRAIL, Genentech, AstraZeneca, Eisai, and Exelixis. K. Rajender Reddy is an advisor to Mallinckrodt, Novo Nordisk, Spark Therapeutics, BioVie; has received research support (Paid to the University of Pennsylvania) from Mallinckrodt, Sequana, Grifols, Exact Sciences, BMS,Intercept, HCC-TARGET, NASH-TARGET; and has served on the data safety monitoring board for Novartis. Jorge A. Marrero has been a consultant for Glycotest (terminated); and has served on the data safety monitoring board of Astra Zeneca.

References

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