GALAD demonstrates high sensitivity for HCC surveillance in a cohort of patients with cirrhosis

Abstract

Background and AimsMost patients with HCC are diagnosed at a late stage, highlighting the need for more accurate surveillance tests. Although biomarkers for HCC early detection have promising data in Phase 2 case- control studies, evaluation in cohort studies is critical prior to adoption in practice. We leveraged a prospective cohort of patients with Child- Pugh A or B cirrhosis who were followed until incident HCC, liver transplantation, death, or loss to follow- up. We used a prospective specimen collection, retrospective, blinded evaluation design for biomarker evaluation of GALAD (gender à age à log alpha- fetoprotein [AFP] à des- gamma- carboxy prothrombin), longitudinal GALAD, and the HCC Early Detection Screening (HES) algorithm- compared to AFP- using patient- level sensitivity and screening- level specificity.Approach and ResultsOf 397 patients with cirrhosis, 42 developed HCC (57.1% early stage) over a median of 2.0 years. Longitudinal GALAD had the highest c- statistic for HCC detection (0.85; 95% CI, 0.77- 0.92) compared to single- time point GALAD (0.79; 95% CI, 0.71- 0.87), AFP (0.77; 95% CI, 0.69- 0.85), and HES (0.76; 95% CI, 0.67- 0.83). When specificity was fixed at 90%, the sensitivity for HCC of single- time point and longitudinal GALAD was 54.8% and 66.7%, respectively, compared to 40.5% for AFP. Sensitivity for HCC detection was higher when restricted to patients with biomarker assessment within 6 months prior to HCC diagnosis, with the highest sensitivities observed for single- time point GALAD (72.0%) and longitudinal GALAD (64.0%), respectively. Sensitivity of single- time point and longitudinal GALAD for early- stage HCC was 53.8% and 69.2%, respectively.ConclusionGALAD demonstrated high sensitivity for HCC detection in a cohort of patients with cirrhosis. Validation of these results is warranted in large Phase 3 data sets.