Performance of GALAD, GAAD, and ASAP for Early HCC Detection in Chronic Liver Disease: A Systematic Review and Meta-Analysis
Mohammad Jarrah, Ashwini Arvind, Purva Gopal, Sneha Deodhar, Ju Dong Yang, Neehar D. Parikh, Amit G. Singal
Abstract
<p>Background: Multi-biomarker panels have shown promise to improve hepatocellular carcinoma (HCC) surveillance in patients with chronic liver disease; however, we lack comparative data on their relative performance for early-stage HCC detection. Methods: We conducted a systematic review of PubMed, Ovid MEDLINE, and Embase databases from January 2010 to November 2024 to identify studies evaluating the performance of three commercially available blood-based biomarker panels (GALAD, GAAD, and ASAP) for HCC surveillance. Pooled estimates were calculated using the DerSimonian and Laird method for a random-effects model. Results: Of 44 eligible studies (n = 33,100 patients) examining HCC surveillance, 37 studies evaluated GALAD, 12 GAAD, and 11 ASAP. Pooled sensitivities of the biomarker panels for early-stage HCC ranged from 70.1% to 74.1%, with pooled specificities ranging from 83.3% to 87.2%. Among studies directly comparing biomarker panels, sensitivity for early-stage HCC did not significantly differ for GALAD versus GAAD (RR 0.96, 95% CI: 0.80–1.15) or GALAD versus ASAP (RR 1.12, 95% CI: 0.79–1.60). The pooled sensitivity of GALAD for early-stage HCC was higher than that of ultrasound among studies directly comparing the two (79.0% [95% CI: 62.2–89.6] versus 73.3% [95% CI: 45.4–90.1], respectively); however, this difference was not statistically significant (RR 1.09, 95% CI: 0.78–1.51). Studies were limited by inclusion of patients with non-cirrhotic liver disease, varying biomarker cutoffs across studies, and high statistical heterogeneity (I2 >50%) for pooled estimates. Conclusion: Multi-biomarker panels including GALAD, GAAD, and ASAP demonstrate promising performance for early-stage HCC detection, supporting their prospective validation for HCC surveillance. </p>