Risk assessment in liver transplantation for hepatocellular carcinoma: long-term follow-up of a two-centre experience
Authors: Wehrle Chase J. , Raj Roma , Maspero Marianna , Satish Sangeeta , Eghtesad Bijan , Pita Alejandro , Kim Jaekeun , Khalil Mazhar , Calderon Esteban , Orabi Danny , Zervos Bobby , Modaresi Esfeh Jamak , Whitsett Linganna Maureen , Diago-Uso Teresa , Fujiki Masato , Quintini Cristiano , Kwon Choon David , Miller Charles , Pinna Antonio , Aucejo Federico , Hashimoto Koji , Schlegel Andrea 
Published: January 2024

Background:
Liver transplantation (LT) is a well-established treatment for hepatocellular carcinoma (HCC), but there are ongoing debates regarding outcomes and selection. This study examines the experience of LT for HCC at a high-volume centre.

Methods:
A prospectively maintained database was used to identify HCC patients undergoing LT from 2000 to 2020 with more than or equal to 3-years follow-up. Data were obtained from the centre database and electronic medical records. The Metroticket 2.0 HCC-specific 5-year survival scale was calculated for each patient. Kaplan–Meier and Cox-regression analyses were employed assessing survival between groups based on Metroticket score and individual donor and recipient risk factors.

Results:
Five hundred sixty-nine patients met criteria. Median follow-up was 96.2 months (8.12 years; interquartile range 59.9–147.8). Three-year recurrence-free (RFS) and overall survival (OS) were 88.6% (n=504) and 86.6% (n=493). Five-year RFS and OS were 78.9% (n=449) and 79.1% (n=450). Median Metroticket 2.0 score was 0.9 (interquartile range 0.9–0.95). Tumour size greater than 3 cm (P=0.012), increasing tumour number on imaging (P=0.001) and explant pathology (P<0.001) was associated with recurrence. Transplant within Milan (P<0.001) or UCSF criteria (P<0.001) had lower recurrence rates. Increasing alpha-fetoprotein (AFP)-values were associated with more HCC recurrence (P<0.001) and reduced OS (P=0.008). Chemoembolization was predictive of recurrence in the overall population (P=0.043) and in those outside-Milan criteria (P=0.038). A receiver-operator curve using Metroticket 2.0 identified an optimal cut-off of projected survival greater than or equal to 87.5% for predicting recurrence. This cut-off was able to predict RFS (P<0.001) in the total cohort and predict both, RFS (P=0.007) and OS (P=0.016) outside Milan. Receipt of donation after brain death (DBD) grafts (55/478, 13%) or living-donor grafts (3/22, 13.6%) experienced better survival rates compared to donation after cardiac death (DCD) grafts (n=15/58, 25.6%, P=0.009). Donor age was associated with a higher HCC recurrence (P=0.006). Both total ischaemia time (TIT) greater than 6hours (P=0.016) and increasing TIT correlated with higher HCC recurrence (P=0.027). The use of DCD grafts for outside-Milan candidates was associated with increased recurrence (P=0.039) and reduced survival (P=0.033).

Conclusion:
This large two-centre analysis confirms favourable outcomes after LT for HCC. Tumour size and number, pre-transplant AFP, and Milan criteria remain important recipient HCC-risk factors. A higher donor risk (i.e. donor age, DCD grafts, ischaemia time) was associated with poorer outcomes.