TY - JOUR
T1 - GALAD demonstrates high sensitivity for HCC surveillance in a cohort of patients with cirrhosis
AU - Singal, Amit G.
AU - Tayob, Nabihah
AU - Mehta, Anand
AU - Marrero, Jorge A
AU - El-Serag, Hashem
AU - Jin, Qingchun
AU - Saenz de Viteri, Cristian
AU - Fobar, Austin
AU - Parikh, Neehar D.
N1 - Funding Information:
Supported by the National Institutes of Health (U01 CA230694, U01 CA230669, and R01 222900). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The funding agencies had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation of the manuscript
Publisher Copyright:
© 2021 American Association for the Study of Liver Diseases.
PY - 2022/3
Y1 - 2022/3
N2 - 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.
AB - 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.
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U2 - 10.1002/hep.32185
DO - 10.1002/hep.32185
M3 - Article
C2 - 34618932
AN - SCOPUS:85121377899
VL - 75
SP - 541
EP - 549
JO - Hepatology
JF - Hepatology
SN - 0270-9139
IS - 3
ER -