Abstract
Despite the development of numerous prognostic models for hepatocellular carcinoma (HCC) recurrence and mortality after liver transplantation, tumor biomarkers such as alpha-fetoprotein (AFP) and protein induced by vitamin K absence-II (PIVKA-II) remain widely used in clinical practice. This study evaluated the performance of AFP and PIVKA-II compared with six prognostic models (RETREAT, SNAPP, MoRAL, R3-AFP, METROTICKET 2.0, and SALT) in a retrospective cohort of 707 adults who underwent living donor liver transplantation (LDLT) for HCC between 2003 and 2018. Patients were stratified into Milan and Beyond Milan groups. Time-dependent receiver operating characteristic curve analysis was conducted using integrated area under the curve (iAUC) and concordance index (C-index) to assess recurrence and mortality. AFP and PIVKA-II (continuous) achieved iAUCs of 0.68-0.75 for recurrence and C-indices of 0.66-0.77 for mortality. Their combination reached iAUCs up to 0.78 and C-indices up to 0.80. Threshold models (AFP ≥200, PIVKA-II ≥400) showed modest predictive performance. Among multivariable models, R3-AFP demonstrated the most consistent performance (iAUC 0.76-0.81; C-index 0.78-0.82). SNAPP, MoRAL, and SALT also performed well. AFP and PIVKA-II may offer practical utility in resource-limited settings. However, multivariable models remain the preferred approach where comprehensive diagnostics are available.