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

Background and Aims Most 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 × age × log alpha‐fetoprotein [AFP] × 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 Results Of 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. Conclusion GALAD 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.