Risk Stratification of Hepatocellular Carcinoma Recurrence After Liver Transplantation: A 25-year Single-center Study Comparing Pre- and Post-transplant Prognostic Models.

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Liver transplantation (LT) is highly effective for HCC, but its main challenge is tumor recurrence, with documented rates between 10% and 20%. This study aims to identify the main independent risk factors for HCC recurrence through a long follow-up, compare the predictive capacity of the most widely accepted criteria, and evaluate the association between radiological-histopathological discrepancies and HCC recurrence in patients undergoing LT.

METHODS

A retrospective observational study including LT recipients with explanted HCC was conducted between 2000 and 2025. Univariate analyses were performed, as well as multivariate analyses and comparative analyses of predictive scores (Milan criteria, alpha-fetoprotein [AFP] model, Metroticket 2.0, and RETREAT).

RESULTS

A total of 272 patients were analyzed, and the overall recurrence rate was 18%. Both pre-transplant AFP >100 ng/mL (subdistribution hazard ratio [sHR] 3.41; 95% confidence interval [CI] 1.54-7.54) and tumor diameter (sHR 1.52; 95% CI 1.16-1.98) were independently associated with an increased risk of HCC recurrence, as were lymphovascular invasion (sHR 5.80; 95% CI 3.10-10.82) and poor tumor differentiation (sHR 12.11; 95% CI 3.84-38.22). Radiological underestimation of tumor diameter was not significantly associated with recurrence risk. The preoperative Metroticket 2.0 demonstrated significantly higher discrimination in the pre-transplant setting, and both RETREAT score and postoperative Metroticket 2.0 showed significantly better performance compared with postoperative Milan criteria after LT.

CONCLUSION

Our 25-year study supports the use of models incorporating both biological and histopathological variables. Some of the resulting clinical implications include the possibility of developing personalized post-transplant surveillance strategies and identifying candidates for adjuvant or preventive therapies.