Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Everolimus Mitigates the Risk of Hepatocellular Carcinoma Recurrence after Liver Transplantation

Paolo De Simone
* ORCID logo ,
Arianna Precisi
,
Quirino Lai
,
Juri Ducci
,
Daniela Campani
,
Piero Marchetti
,
Stefano Gitto
,
Laura Crocetti
ORCID logo
Version 1 : Received: 12 January 2024 / Approved: 12 January 2024 / Online: 15 January 2024 (10:26:22 CET)

A peer-reviewed article of this Preprint also exists.

De Simone, P.; Precisi, A.; Lai, Q.; Ducci, J.; Campani, D.; Marchetti, P.; Gitto, S. Everolimus Mitigates the Risk of Hepatocellular Carcinoma Recurrence after Liver Transplantation. Cancers 2024, 16, 1243. De Simone, P.; Precisi, A.; Lai, Q.; Ducci, J.; Campani, D.; Marchetti, P.; Gitto, S. Everolimus Mitigates the Risk of Hepatocellular Carcinoma Recurrence after Liver Transplantation. Cancers 2024, 16, 1243.

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 (5.9ng/mL; P<0.001) showed lower recurrence rates versus TAC. Based on our experience, everolimus provides a reduction of 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.

Keywords

liver transplantation; immunosuppression; everolimus; hepatocellular carcinoma; recurrence

Subject

Medicine and Pharmacology, Transplantation

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Download PDF

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0
Get PDF Cite Share 0
Bookmark BibSonomy Mendeley Reddit Delicious
×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.