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Performance of GAAD and GALAD Biomarker Panels for HCC Detection in Patients with MASLD or ALD Cirrhosis
Mohammad Jarrah1, Sneha Deodhar1, Lisa Quirk1
1Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75235, USA.
Insights
Blood tests GAAD and GALAD show high sensitivity for detecting early hepatocellular carcinoma (HCC) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) or alcohol-associated liver disease (ALD). These biomarkers may improve surveillance for HCC in at-risk populations.
Area of Science:
- Hepatology
- Biomarker Discovery
- Oncology
Background:
- Abdominal ultrasound has limitations in hepatocellular carcinoma (HCC) surveillance, especially in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) or alcohol-associated liver disease (ALD).
- There is a growing need for alternative surveillance strategies, such as blood-based biomarkers, for early HCC detection.
Purpose of the Study:
- To evaluate the performance of two blood-based biomarker panels, GAAD and GALAD, for detecting early-stage HCC (Barcelona Clinic Liver Cancer stage 0 or A).
- To compare the sensitivity and specificity of GAAD and GALAD against ultrasound plus alpha fetoprotein (AFP) in patients with MASLD or ALD cirrhosis.
Main Methods:
- A case-control study was conducted with patients diagnosed with HCC and controls with cirrhosis but without HCC.
- Blood specimens were analyzed for GAAD and GALAD scores using the Roche Elecsys platform with validated cutoffs.
- Sensitivity and specificity were compared between biomarker panels and ultrasound plus AFP using McNemar's chi square test.
Main Results:
- GAAD and GALAD achieved 87.2% sensitivity for early-stage HCC, with specificities of 69.1% and 67.9%, respectively.
- In paired analyses, GAAD showed higher sensitivity for any-stage HCC (89.5%) compared to ultrasound plus AFP (68.4%, p=0.046).
- Both GAAD and GALAD demonstrated consistently higher sensitivity than ultrasound plus AFP across various patient subgroups.
Conclusions:
- GAAD and GALAD exhibit high sensitivity for detecting early-stage HCC in patients with non-viral cirrhosis.
- These blood-based biomarkers show potential for improving HCC surveillance in contemporary patient populations.
- Further validation is warranted to establish their role in routine clinical practice.
Abstract:
Background: Abdominal ultrasound is prone to hepatocellular carcinoma (HCC) surveillance failure, particularly in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) or alcohol-associated liver disease (ALD), prompting growing interest in blood-based biomarkers as an alternative strategy. Methods: We conducted a case-control study evaluating two blood-based biomarker panels, GAAD and GALAD, for detection of early-stage HCC (Barcelona Clinic Liver Cancer (BCLC) stage 0 or A) in patients with MASLD or ALD cirrhosis. Blood specimens were collected within 6 months of HCC diagnosis (cases); controls were patients with cirrhosis but without HCC. GAAD and GALAD scores were measured using the Roche Elecsys platform, applying validated cutoffs of 2.57 and 2.47, respectively. Sensitivity and specificity were compared between the panels and versus ultrasound plus alpha fetoprotein (AFP) using McNemar's chi square test. Results: Of 152 patients (56.6% men), 46.7% had HCC (54.9% BCLC 0/A) and 53.3% had cirrhosis without HCC. GAAD and GALAD each achieved a sensitivity of 87.2% for early-stage HCC, with specificities of 69.1% and 67.9%, respectively. In paired analyses (n = 90), GAAD had higher sensitivity for any-stage HCC (89.5% vs. 68.4%, p = 0.046) but lower specificity (71.8% vs. 93.0%, p = 0.006) than ultrasound plus AFP. GAAD and GALAD demonstrated consistently higher sensitivity than ultrasound plus AFP across subgroups by age, sex, cirrhosis etiology, and Child Pugh class. Conclusion: In this case-control study of patients with non-viral cirrhosis, GAAD and GALAD demonstrated high sensitivity for early-stage HCC. These findings highlight the potential of blood-based biomarkers to improve HCC surveillance in contemporary populations.
