GALAD Score for Hepatocellular Carcinoma Detection in Comparison with Liver Ultrasound and Proposal of GALADUS Score

Abstract

Background: The GALAD score is a serum biomarkerbased model that predicts the probability of having hepatocellular carcinoma (HCC) in patients with chronic liver disease. We aimed to assess the performance of the GALAD score in comparison with liver ultrasound for detection of HCC.Methods: A single-center cohort of 111 HCC patients and 180 controls with cirrhosis or chronic hepatitis B and a multicenter cohort of 233 early HCC and 412 cirrhosis patients from the Early Detection Research Network (EDRN) phase II HCC Study were analyzed.Results: The area under the ROC curve (AUC) of the GALAD score for HCC detection was 0.95 [95% confidence interval (CI), 0.93-97], which was higher than the AUC of ultrasound (0.82, P <0.01). At a cutoff of À0.76, the GALAD score had a sensitivity of 91% and a specificity of 85% for HCC detection. The AUC of the GALAD score for early-stage HCC detection remained high at 0.92 (95% CI, 0.88-0.96; cutoff À1.18, sensitivity 92%, specificity 79%). The AUC of the GALAD score for HCC detection was 0.88 (95% CI, 0.85-0.91) in the EDRN cohort. The combination of GALAD and ultrasound (GALADUS score) further improved the performance of the GALAD score in the single-center cohort, achieving an AUC of 0.98 (95% CI, 0.96-0.99; cutoff À0.18, sensitivity 95%, specificity 91%). a For the calculation of AUC, the continuous GALAD score is used, whereas for sensitivity and specificity, we used the GALAD cutoff. b P value looking at difference in AUC between GALAD and ultrasound.Yang et al.

GALAD Score Detects Early Hepatocellular Carcinoma in an International Cohort of Patients With Nonalcoholic Steatohepatitis

“…The lower performance in the USS-American cohort might be caused by smaller group sizes (30 NASH-HCC, 49 non-HCC NASH) in this etiology. Interestingly, Yang et al 11 identified the ideal GALAD cutoff to detect NASH-HCC at -0.86, which is between the established cutoff and the one identified by us.…”

“…significantly superior to USS for HCC detection. However, Yang et al 11 found only an AUC of 0.89 for NASH-specific HCC detection by GALAD, which was not significantly better than USS. In the present multicenter study of NASH-HCC patients we demonstrate an excellent performance of the GALAD for detection of NASH HCC (AUC, 0.96).…”

“…10 A subsequent multicenter case-control study demonstrated that the GALAD model was superior to USS in early HCC detection, independent of etiology. 11 Although the latest American Association for the Study of Liver Diseases guidelines note the potential of the GALAD score for HCC surveillance, it remarks on the need for phase III validation before adoption in routine clinical practice. 3 The limitations of USS alone for early detection of HCC are particularly evident in patients with NASH.…”

“…23,34 In addition the GALAD model separated HCC from pancreatic adenocarcinoma/ cholangiocarcinoma (AUC, 0.95), 23 suggesting that GALAD is specific for HCC. In a recent, large American cohort study by Yang et al, 11 including patients from the Early Detection Research Network Phase 2 HCC Study, the performance of GALAD over all etiologies was Figure 3. Rise of GALAD in NAFLD patients under surveillance occurs before HCC diagnosis.…”

Early Detection of Hepatocellular Carcinoma: Expanding the Utility of Circulating Tumor Markers

“…The use of DCP for surveillance in conjunction with AFP and AFP‐L3 is common in practice and endorsed by clinical practice guidelines in China and Japan. All three tumor markers are incorporated in the GALAD (gender, age, AFP‐L3, AFP, and DCP) score, which has been validated extensively . DCP may perform better in the setting of advanced tumor stage with portal vein invasion.…”