Integrating Alpha-Fetoprotein and Protein Induced by Vitamin K Antagonist-II as Surveillance Tools After Liver Transplantation for Hepatocellular Carcinoma: A Novel Protocol for Early Detection of Tumor Recurrence

Hepatocellular carcinoma (HCC) is a cancer prevalent worldwide, and liver transplantation (LT) is a curative treatment option. However, post-transplantation recurrence remains a significant concern, necessitating the identification of predictive factors and early detection of patients with recurrence. Alpha-fetoprotein (AFP) and proteins induced by vitamin K absence-II (PIVKA-II) are recognized HCC diagnostic markers. However, standardized protocols for testing intervals and supplemental imaging incorporation are limited. This study explored the integration of both tumor markers as surveillance tools and suggested different surveillance protocols based on recurrence risk. We conducted a retrospective analysis of 708 patients who underwent living donor liver transplantation (LDLT) for HCC. Patients were categorized into four groups based on models for tumor recurrence after liver transplantation (MoRAL) scores and tumor marker normalization after LT. Group 1, with the lowest risk, showed 12.5% recurrence at 15 months, whereas Group 4 showed 96.2% recurrence within 5 months. Integrating AFP and PIVKA-II yielded an overall 82% sensitivity for recurrence detection. As 28.0% of patients with HCC recurrence in Group 1 revealed recurrence without tumor marker elevation, we propose a novel HCC surveillance protocol with differentiated intervals based on specific risk groups. This approach is promising for enhancing early detection and post-transplantation outcomes.