Beyond Size and Number: The Predictive Power of Pre-Transplant AFP and Tumor Morphology on HCC Recurrence After Liver Transplantation

Objective: The primary aim of this study was to evaluate the predictive value of pre-transplant Alpha-fetoprotein (AFP) levels combined with tumor morphological features (number, size, and localization) on early and late hepatocellular carcinoma (HCC) recurrence following liver transplantation. The secondary aim was to assess the impact of these variables, along with tumor differentiation, vascular invasion, and response to pre-transplant locoregional therapies, on overall survival and postoperative mortality.Method: A total of 77 patients (M/F: 68/9, mean age 62.6) who underwent liver transplantation for HCC were retrospectively analyzed. Preoperative AFP levels, AFP scores, radiological tumor burden, and explant pathology results were retrieved from medical records. Primary endpoints were overall recurrence, early (12-month) and late (24-month) recurrence rates, and overall survival. Mann-Whitney U test and Kruskal-Wallis H test were used for statistical analysis.Results: During a mean follow-up of 1305 days, the overall recurrence rate was 19.48% (n=15). Patients with recurrence had significantly larger maximum tumor diameters (35.13 ± 11.96 mm vs. 28.03 ± 17.34 mm; p=0.048) and a higher number of tumor nodules (3.67 ± 3.29 vs. 2.03 ± 1.68; p=0.022). Pre-transplant baseline AFP levels were significantly higher in patients who developed recurrence within 24 months compared to those who did not (146.99 ng/mL vs. 42.11 ng/mL; p=0.049). Furthermore, patients who exceeded the Milan criteria had significantly higher AFP scores than those within the criteria (3.09 vs. 1.67; p=0.032). Patients experiencing early recurrence (within 12 months) were significantly younger (57 vs. 63 years; p=0.040).Conclusion: Preoperative AFP levels, along with increased tumor diameter and nodule count, are strong complementary predictors of postoperative HCC recurrence. In candidate selection and post-transplant risk stratification, incorporating biological markers, such as AFP, alongside morphological features is crucial, rather than relying solely on traditional static criteria.