文章：

依维莫司降低肝移植后肝细胞癌复发风险

Everolimus Mitigates the Risk of Hepatocellular Carcinoma Recurrence after Liver Transplantation

原文发布日期：22 March 2024

DOI: 10.3390/cancers16071243

类型: Article

开放获取: 是

英文摘要：

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.

摘要翻译： 

为获取依维莫司在肝细胞癌肝移植患者中长期应用的数据，我们对2013年至2021年间接受移植的成年受者进行了单中心回顾性分析。采用逆概率加权法将含依维莫司的免疫抑制方案患者与他克莫司方案患者进行匹配，最终形成两组倾向性匹配队列：依维莫司组233例（45.6%）与他克莫司组278例（54.4%）。中位随访时间4.4年（四分位距3.8年）显示，依维莫司组复发风险显著低于他克莫司组（7.7% vs 16.9%；相对风险比=0.45；p=0.002）。多变量分析表明：微血管浸润（风险比=1.22；p<0.04）和较高肿瘤分级（风险比=1.27；p<0.04）与较高复发率相关，而符合米兰标准（风险比=0.56；p<0.001）、成功实施移植前降期治疗（风险比=0.63；p=0.01）及使用依维莫司（风险比=0.46；p<0.001）对降低移植后复发风险具有积极作用。在依维莫司治疗亚组中，早期用药（≤30天；p<0.001）、较长治疗时长（p<0.001）及较高血药浓度（≥5.9 ng/mL；p<0.001）患者复发率显著低于他克莫司组。本研究证实，依维莫司可降低肝细胞癌复发相对风险，尤其对晚期患者及早期用药、高血药浓度、长期治疗者效果显著。这些数据支持肝移植后早期启用依维莫司治疗，以降低慢性免疫抑制导致的移植物损耗率。

原文链接：

Everolimus Mitigates the Risk of Hepatocellular Carcinoma Recurrence after Liver Transplantation