GALAD Score Performs Better in Diagnosis of HCC Than AFP in Patients with Chronic Hepatitis C Infection

Abstract

Introduction: The GALAD score (Gender, Age, Alphafetoprotein-L3% (AFP-L3%), Alpha-fetoprotein (AFP), Des-Gamma Carboxy Prothrombin (DCP)) is a statistical model developed for screening and diagnosis of hepatocellular carcinoma (HCC) in high-risk individuals. GALAD has been validated to have superior performance when compared to individual serum biomarkers in European, Asian, and US cohorts. Performance of serum biomarker based screening strategies has been shown to vary based on etiology of underlying liver disease. Particularly, AFP has been shown to have lower sensitivity and specifi city for diagnosing HCC in patients with chronic hepatitis C virus (HCV) infection. Using our GALAD score validation cohort at our institution, we compared performance of the GALAD score to that of other biomarkers in patient with different etiologies of liver disease, including HCV. Methods: A single center retrospective study was performed on patients with cirrhosis undergoing HCC screening with liver ultrasound and measurement of serum AFP, AFP-L3%, and DCP. Diagnosis of HCC was made by dynamic contrast CT or MRI of the liver or biopsy. Patients without HCC were followed for at least 6 months or had negative CT, MRI, or biopsy. Serum biomarkers were measured using the WAKO μTASWako i30 Immunoanalyzer. GALAD score was calculated as -10.08 + 1.67 x [Gender (1 for male, 0 for female)] + 0.09 x [Age] + 0.04 x [AFP-L3%] + 2.34 x log[AFP] + 1.33 x log[DCP]. The area under the Receiver Operating Characteristic Curve (AUROC) was calculated for each biomarker and for the GALAD score. Subgroup analysis based on etiology of underlying liver disease was also performed. Results: 103 patients with HCC and 128 patients with cirrhosis were included. For all patients together, the GALAD score had AUROC of 0.93, while AFP, AFP-L3%, and DCP had AUROCs of 0.89, 0.79, and 0.78, respectively. Notably, for patients with HCV (41 with HCC, and 20 without HCC), the AUROC for GALAD score was 0.96, while AFP, AFP-L3%, and DCP had AUROCs of 0.88, 0.77, and 0.84. When comparing performance of GALAD score to AFP, GALAD score performed also superiorly for patients with HBV with or without cirrhosis, NASH cirrhosis, and all other etiologies of cirrhosis (AUROCs 0.99 vs 0.96, 0.88 vs 0.86, and 0.95 vs 0.90, respectively). Conclusion: Our findings suggest that GALAD score would be a better serum biomarker based HCC surveillance strategy than AFP, particularly in populations where HCV is a leading cause of HCC.