Prediction of microvascular invasion and post-resection prognosis using ADV, AFP-PIVKA-II, and MoRAL scores in hepatocellular carcinoma patients: an international multicenter cohort study with 9,061 patients.

Purpose: Microvascular invasion (MVI) is a well-known pathological prognostic factor in hepatocellular carcinoma (HCC). This study aimed to predict MVI and to assess post-resection prognosis using the ADV (multiplication of AFP, des-γ-carboxyprothrombin-also known as proteins induced by vitamin K absence or antagonist-II [PIVKA-II], and tumor volume), AP (multiplication of AFP and PIVKA-II), and MoRAL (model to predict tumor recurrence [TR] after liver transplantation) scores. Methods: This international multicenter study included 9,061 patients who underwent hepatic resection for solitary HCC measuring 1.0-10 cm from 2010 to 2017 at ten Korean centers and 73 Japanese centers, and were followed up until 2020. Results: The receiver operating characteristic (ROC) area under the curve (AUC) for diagnosis of MVI was 0.734 for the ADV score at 4.7log, 0.684 for the AP score at 3.7log, and 0.705 for the MoRAL score at 162.0. The ADV score exhibited the strongest predictive ability for MVI. The ROC AUC for actuarial 5-year TR was 0.586 for the ADV score, 0.583 for the AP score, and 0.586 for the MoRAL score, demonstrating similar prognostication efficacy. The hazard ratios for TR and overall survival demonstrated strong, stepwise positive correlations with increases in both the ADV and AP scores, but not the MoRAL score. Conclusions: The ADV score is a superior integrated biomarker for predicting post-resection prognosis in patients with HCC, outperforming both the AP and MoRAL scores. The AP score appears to be a simplified alternative to the ADV score, particularly in cases of small HCC.