GALAD Score Detects Early-Stage Hepatocellular Carcinoma in a European Cohort of Chronic Hepatitis B and C Patients

Abstract

Despite vaccination programs and direct antiviral treatments, the incidence of virus-related hepatocellular carcinoma (HCC) remains high, while ultrasound-based detection rates for early-stage HCC is continuously low. To address this insufficiency, we set out to characterize whether the GALAD score, which incorporates gender, age, and serum levels of AFP, AFP isoform L3 (AFP-L3), and des-gamma-carboxy-prothrombin (DCP), can improve early-stage HCC detection in a Caucasian HBV/HCV cohort. In a retrospective German single-center study, 182 patients with HBV, 223 with HCV and 168 with other etiology (OE) of chronic liver disease (CLD) were enrolled. HCC was confirmed in 52 HBV, 84 HCV and 60 OE CLD patients. The diagnostic performance of the single biomarkers in HCC detection was compared to the GALAD model. At initial diagnosis, most patients were at (very) early BCLC 0 (n = 14/7%) or A (n = 56/29%) or intermediate stage BCLC B (n = 93/47%) HCC in all three subgroups. In the BCLC 0/A cohort, GALAD exhibited an AUC of 0.94 discriminating HCC from non-HCC, surpassing AFP (AUC 0.86), AFP-L3 (AUC 0.83) and DCP (AUC 0.83). In the HBV population, GALAD achieved an AUC of 0.96, in HCV an AUC of 0.98 and in OE an AUC of 0.99, clearly superior to the biomarkers alone. Furthermore, in HCV patients GALAD showed a significantly higher specificity (89%) versus AFP (64%) alone. In chronic viral hepatitis, the GALAD model showed superior performance in detection of early-stage HCC, while exhibiting higher specificity in HCV patients compared to AFP alone. We conclude that the GALAD score shows potential for HCC surveillance in Caucasian HBV/HCV patients.

Keywords: AFP; AFP-L3; DCP; GALAD; HBV; HCC; HCV; chronic hepatitis B; chronic hepatitis C; hepatocellular carcinoma.

Figure 1

GALAD in early-HCC and intermediate to advanced HCC. (a) ROC-Curve for GALAD, AFP, AFP-L3, DCP, GALAD in early HCC (BCLC 0/A); (b) ROC-Curve for GALAD, AFP, AFP-L3, DCP in intermediate to advanced stage HCC (BCLC B/C/D); DeLong test p ≤ 0.001. GALAD: gender, age, AFP-L3, AFP, DCP score, HCC: hepatocellular carcinoma, HBV: chronic hepatitis B infection, HCV: chronic hepatitis C infection, AFP: alpha-fetoprotein, AFP-L3: ratio of LCA-reactive AFP to total AFP, DCP: des-gamma-carboxyprothrombin, AUC: area under the curve, CI: confidence interval.

Figure 2

ROC-curve for GALAD vs. individual biomarkers in all etiologies. ROC-Curve for GALAD, AFP, AFP-L3 and DCP for HCC detection; (a) all patients, (b) HBV, (c) HCV, (d) others. DeLong test p-Value: All p-values ≤ 0.001. HCC: hepatocellular carcinoma, HBV: chronic hepatitis B infection, HCV: chronic hepatitis C infection, AFP: alpha-fetoprotein, AFP-L3: ratio of LCA-reactive AFP to total AFP, DCP: des-gamma-carboxyprothrombin, AUC: area under the curve, CI: confidence interval.