AUTHOR=Gongor Saran Ochir , Choi YoungRok , Kim Gayoung , Kim Min Kyoung , Park Sang Hyuk , Kim Jiyoung , Kim Jae-Yoon , Hong Su young , Lee Jeong-Moo , Hong Suk Kyun , Lee Kwang-Woong TITLE=Long-Term Prognostic Value of AFP and PIVKA-II in HCC After Living Donor Liver Transplantation: A Single-Center Retrospective Study JOURNAL=Transplant International VOLUME=Volume 38 - 2025 YEAR=2025 URL=https://www.frontierspartnerships.org/journals/transplant-international/articles/10.3389/ti.2025.14748 DOI=10.3389/ti.2025.14748 ISSN=1432-2277 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.