A Statistical Approach to the Diagnosis and Prediction of HCC Using CK19 and Glypican 3 Biomarkers

Abstract

Various statistical models predict the probability of developing hepatocellular carcinoma (HCC) in patients with cirrhosis, with GALAD being one of the most extensively studied scores. Biomarkers like alpha-fetoprotein (AFP), AFP-L3, and des-g-carboxyprothrombin (DCP) are widely used alone or in conjunction with ultrasound to screen for HCC. Our study aimed to compare the effectiveness of Cytokeratin 19 (CK19) and Glypican-3 (GPC3) as standalone biomarkers and in a statistical model to predict the likelihood of HCC. We conducted a monocentric prospective study involving 154 participants with previously diagnosed liver cirrhosis, divided into two groups: 95 patients with confirmed HCC based on clinical, biological, and imaging features and 59 patients without HCC. We measured the levels of AFP, AFP-L3, DCP, GPC3, and CK19 in both groups. We used univariate and multivariate statistical analyses to evaluate the ability of GPC3 and CK19 to predict the presence of HCC and incorporated them into a statistical model—the GALKA score—which was then compared to the GALAD score. AFP performed better than AFP-F3, DCP, GPC3, and CK19 in predicting the presence of HCC in our cohort. Additionally, GPC3 outperformed CK19. We used multivariate analysis to compute the GALKA score to predict the presence of HCC. Using these predictors, the following score was formulated: 0.005*AFP-L3 + 0.00069*AFP + 0.000066*GPC3 + 0.01*CK19 + 0.235*Serum Albumin—0.277. The optimal cutoff was >0.32 (AUROC = 0.98, sensitivity: 96.8%, specificity: 93%, positive predictive value—95.8%, negative predictive value—94.8%). The GALKA score had a similar predictive value to the GALAD score for the presence of HCC. In conclusion, AFP, AFP-L3, and DCP were the best biomarkers for predicting the likelihood of HCC. Our score performed well overall and was comparable to the GALAD score.

Chinese expert consensus statement on the clinical application of AFP/AFP‐L3%/DCP using GALAD and GALAD‐like algorithm in HCC

“…In an Italy cohort, the diagnostic efficacy of GALAD (AUC: 0.98) was better than the triple‐biomarker combination only (AUC: 0.95) 92 . Studies from different groups indicated that the AUC of the GALAD for HCC detection were all above 0.95 93–95 …”

“… 92 Studies from different groups indicated that the AUC of the GALAD for HCC detection were all above 0.95. 93 , 94 , 95 …”