Background/Aims This study aimed to investigate whether everolimus (EVR) affects long-term survival after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC).
Methods The data from 303 consecutive patients with HCC who had undergone LT from January 2012 to July 2018 were retrospectively reviewed. The patients were divided into two groups: 1) patients treated with EVR in combination with calcineurin inhibitors (CNIs) (EVR group; n=114) and 2) patients treated with CNI-based therapy without EVR (non-EVR group; n=189). Time to recurrence (TTR) and overall survival (OS) after propensity score (PS) matching were compared between the groups, and prognostic factors for TTR and OS were evaluated.
Results The EVR group exhibited more aggressive tumor biology than the non-EVR group, such as a higher number of tumors (P=0.003), a higher prevalence of microscopic vascular invasion (P=0.017) and exceeding Milan criteria (P=0.029). Compared with the PS-matched non-EVR group, the PS-matched EVR group had significantly better TTR (P<0.001) and OS (P<0.001). In multivariable analysis, EVR was identified as an independent prognostic factor for TTR (hazard ratio [HR], 0.248; P=0.001) and OS (HR, 0.145; P<0.001).
Conclusions Combined with CNIs, EVR has the potential to prolong long-term survival in patients undergoing LT for HCC. These findings warrant further investigation in a well-designed prospective study.
Citations
Citations to this article as recorded by
Everolimus Personalized Therapy: Second Consensus Report by the International Association of Therapeutic Drug Monitoring and Clinical Toxicology Satohiro Masuda, Florian Lemaitre, Markus J. Barten, Stein Bergan, Maria Shipkova, Teun van Gelder, Sander Vinks, Eberhard Wieland, Kirsten Bornemann-Kolatzki, Mercè Brunet, Brenda de Winter, Maja-Theresa Dieterlen, Laure Elens, Taihei Ito, Kamisha Johnso Therapeutic Drug Monitoring.2025; 47(1): 4. CrossRef
Genetic alterations are related to clinicopathological features and risk of recurrence/metastasis of hepatocellular carcinoma Lili Meng, Zhenjian Jiang, Guangyue Shen, Shulan Lin, Feng Gao, Xinxin Guo, Bin Lv, Shuying Hu, Zheng Ni, Shanghua Chen, Yuan Ji European Journal of Cancer Prevention.2025; 34(5): 456. CrossRef
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