GALAD demonstrates high sensitivity for HCC surveillance in a cohort of patients with cirrhosis

Hepatology. 2022 Mar;75(3):541-549. doi: 10.1002/hep.32185. Epub 2021 Dec 17.


Background and aims: Most patients with HCC are diagnosed at a late stage, highlighting the need for more accurate surveillance tests. Although biomarkers for HCC early detection have promising data in Phase 2 case-control studies, evaluation in cohort studies is critical prior to adoption in practice. We leveraged a prospective cohort of patients with Child-Pugh A or B cirrhosis who were followed until incident HCC, liver transplantation, death, or loss to follow-up. We used a prospective specimen collection, retrospective, blinded evaluation design for biomarker evaluation of GALAD (gender × age × log alpha-fetoprotein [AFP] × des-gamma-carboxy prothrombin), longitudinal GALAD, and the HCC Early Detection Screening (HES) algorithm-compared to AFP-using patient-level sensitivity and screening-level specificity.

Approach and results: Of 397 patients with cirrhosis, 42 developed HCC (57.1% early stage) over a median of 2.0 years. Longitudinal GALAD had the highest c-statistic for HCC detection (0.85; 95% CI, 0.77-0.92) compared to single-time point GALAD (0.79; 95% CI, 0.71-0.87), AFP (0.77; 95% CI, 0.69-0.85), and HES (0.76; 95% CI, 0.67-0.83). When specificity was fixed at 90%, the sensitivity for HCC of single-time point and longitudinal GALAD was 54.8% and 66.7%, respectively, compared to 40.5% for AFP. Sensitivity for HCC detection was higher when restricted to patients with biomarker assessment within 6 months prior to HCC diagnosis, with the highest sensitivities observed for single-time point GALAD (72.0%) and longitudinal GALAD (64.0%), respectively. Sensitivity of single-time point and longitudinal GALAD for early-stage HCC was 53.8% and 69.2%, respectively.

Conclusion: GALAD demonstrated high sensitivity for HCC detection in a cohort of patients with cirrhosis. Validation of these results is warranted in large Phase 3 data sets.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Biomarkers / blood*
  • Biomarkers, Tumor / analysis*
  • Carcinoma, Hepatocellular / diagnosis*
  • Carcinoma, Hepatocellular / etiology
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / surgery
  • Early Detection of Cancer / methods*
  • Female
  • Humans
  • Liver Cirrhosis* / blood
  • Liver Cirrhosis* / complications
  • Liver Cirrhosis* / diagnosis
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / etiology
  • Liver Neoplasms / mortality
  • Liver Neoplasms / surgery
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Predictive Value of Tests
  • Protein Precursors / blood*
  • Prothrombin
  • Sensitivity and Specificity
  • United States
  • alpha-Fetoproteins / analysis*


  • Biomarkers
  • Biomarkers, Tumor
  • Protein Precursors
  • alpha-Fetoproteins
  • acarboxyprothrombin
  • Prothrombin