Everolimus Mitigates the Risk of Hepatocellular Carcinoma Recurrence after Liver Transplantation
by
,
Paolo De Simone
1,2,*,
Arianna Precisi
3,
Quirino Lai
4,
Juri Ducci
5,
Daniela Campani
2,6,
Piero Marchetti
7 and
Stefano Gitto
8,9 1
Liver Transplant Program, University of Pisa Medical School Hospital, 56124 Pisa, Italy
2
Department of Surgical, Medical, Biochemical Pathology and Intensive Care, University of Pisa, 56126 Pisa, Italy
3
Transplant Laboratory, University of Pisa Medical School Hospital, 56126 Pisa, Italy
4
AOU Umberto I Policlinico of Rome, Sapienza University of Rome, 00161 Rome, Italy
5
Azienda Ospedaliero Universitaria Pisana, 56124 Pisa, Italy
6
Department of Pathology, University of Pisa Medical School Hospital, 56124 Pisa, Italy
7
Diabetology Unit, University of Pisa Medical School Hospital, 56124 Pisa, Italy
8
Internal Medicine and Liver Unit, University Hospital Careggi, 50134 Florence, Italy
9
Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
*
Author to whom correspondence should be addressed.
Cancers 2024, 16(7), 1243; https://doi.org/10.3390/cancers16071243
Submission received: 12 January 2024
/
Revised: 10 March 2024
/
Accepted: 19 March 2024
/
Published: 22 March 2024
(This article belongs to the Special Issue Advances and Future Developments in Liver Transplantation for Cancers)
Simple Summary
Everolimus is an immunosuppressive drug used to prevent rejection after liver transplantation. It is an attractive alternative to tacrolimus for patients with hepatocellular carcinoma who are undergoing liver transplantation due to its antiproliferative effects. In our study, we investigated whether liver transplant patients who received everolimus after transplantation had a reduced risk of hepatocellular carcinoma recurrence compared to those on tacrolimus. In a group of 511 patients, recipients treated with everolimus exhibited a reduced risk of tumor recurrence after transplantation. This was particularly true for patients with more advanced tumors and who received the drug earlier and for longer periods. We recommend including everolimus in the post-transplant immunosuppressive regimen to optimize outcomes of liver transplantation for hepatocellular carcinoma.
Abstract
To obtain long-term data on the use of everolimus in patients who underwent liver transplantation for hepatocellular carcinoma, we conducted a retrospective, single-center analysis of adult recipients transplanted between 2013 and 2021. Patients on everolimus-incorporating immunosuppression were matched with those on tacrolimus using an inverse probability of treatment weighting methodology. Two propensity-matched groups of patients were thus compared: 233 (45.6%) receiving everolimus versus 278 (54.4%) on tacrolimus. At a median (interquartile range) follow-up of 4.4 (3.8) years after transplantation, everolimus patients showed a reduced risk of recurrence versus tacrolimus (7.7% versus 16.9%; RR = 0.45; p = 0.002). At multivariable analysis, microvascular infiltration (HR = 1.22; p < 0.04) and a higher tumor grading (HR = 1.27; p < 0.04) were associated with higher recurrence rate while being within Milan criteria at transplant (HR = 0.56; p < 0.001), a successful pre-transplant downstaging (HR = 0.63; p = 0.01) and use of everolimus (HR = 0.46; p < 0.001) had a positive impact on the risk of post-transplant recurrence. EVR patients with earlier drug introduction (≤30 days; p < 0.001), longer treatment duration (p < 0.001), and higher drug exposure (≥5.9 ng/mL; p < 0.001) showed lower recurrence rates versus TAC. Based on our experience, everolimus provides a reduction in the relative risk of hepatocellular carcinoma recurrence, especially for advanced-stage patients and those with earlier drug administration, higher drug exposure, and longer time on treatment. These data advocate for early everolimus introduction after liver transplantation to reduce the attrition rate consequent to chronic immunosuppression.
