학술논문

Everolimus Mitigates the Risk of Hepatocellular Carcinoma Recurrence after Liver Transplantation.
Document Type
Article
Source
Cancers. Apr2024, Vol. 16 Issue 7, p1243. 18p.
Subject
*RISK assessment
*CANCER relapse
*PATIENTS
*TRANSPLANTATION of organs, tissues, etc.
*CANCER invasiveness
*PROBABILITY theory
*RETROSPECTIVE studies
*DESCRIPTIVE statistics
*MULTIVARIATE analysis
*TUMOR grading
*TREATMENT duration
*RELATIVE medical risk
*TACROLIMUS
*EVEROLIMUS
*COMPARATIVE studies
*LIVER transplantation
*HEPATOCELLULAR carcinoma
*IMMUNOSUPPRESSION
*PATIENT aftercare
*DISEASE risk factors
Language
ISSN
2072-6694
Abstract
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. 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. [ABSTRACT FROM AUTHOR]