Everolimus-facilitated reduced-exposure tacrolimus (EVR + rTAC) at 30 days after liver transplantation (LT) has shown advantages in renal preservation. This study evaluated the effects of early initiation of EVR + rTAC in de novo LT recipients (LTRs). In HEPHAISTOS (NCT01551212, EudraCT 2011-003118-17), a 12-month, multicenter, controlled study, LTRs were randomly assigned at 7 to 21 days after LT to receive EVR + rTAC or standard-exposure tacrolimus (sTAC) with steroids. The primary objective was to demonstrate superior renal function (assessed by estimated glomerular filtration rate [eGFR]) with EVR + rTAC versus sTAC at month 12 in the full analysis set (FAS). Other assessments at month 12 included the evaluation of renal function in compliance set and on-treatment (OT) patients, efficacy (composite endpoint of graft loss, death, or treated biopsy-proven acute rejection [tBPAR] and individual components) in FAS, and safety. In total, 333 patients (EVR + rTAC, 169; sTAC, 164) were included in the FAS. A high proportion of patients was nonadherent in maintaining tacrolimus trough levels (EVR + rTAC, 36.1%; sTAC, 34.7%). At month 12, the adjusted least square mean eGFR was numerically higher with EVR + rTAC versus sTAC (76.2 versus 72.1 mL/minute/1.73 m², difference: 4.1 mL/minute/1.73 m²; P = 0.097). A significant difference of 8.3 mL/minute/1.73 m² (P = 0.03) favoring EVR + rTAC was noted in the compliance set. Incidence of composite efficacy endpoint (7.7% versus 7.9%) and tBPAR (7.1% versus 5.5%) at month 12 as well as incidence of treatment-emergent adverse events (AEs) and serious AEs were comparable between groups. A lower proportion of patients discontinued EVR + rTAC than sTAC treatment (27.2% versus 34.1%). Early use of everolimus in combination with rTAC showed comparable efficacy, safety, and well-preserved renal function versus sTAC therapy at month 12. Of note, renal function was significantly enhanced in the compliance set.

中文翻译：

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肝移植中早期依维莫司促进减少他克莫司：来自随机 HEPHAISTOS 试验的结果

在肝移植 (LT) 后 30 天，依维莫司促进减少暴露他克莫司 (EVR + rTAC) 在肾脏保存方面显示出优势。本研究评估了早期开始 EVR + rTAC 对新 LT 接受者 (LTR) 的影响。在 HEPHAISTOS (NCT01551212, EudraCT 2011-003118-17) 中，一项为期 12 个月的多中心对照研究在 LT 后 7 至 21 天随机分配 LTR 接受 EVR + rTAC 或标准暴露他克莫司 (sTAC) 和类固醇。主要目标是在第 12 个月的完整分析集 (FAS) 中证明 EVR + rTAC 与 sTAC 相比具有更好的肾功能（通过估计的肾小球滤过率 [eGFR] 评估）。第 12 个月的其他评估包括依从性组和治疗中 (OT) 患者的肾功能评估、疗效（移植物丢失、死亡、或经活检证实的急性排斥反应 [tBPAR] 和个别成分）在 FAS 中的疗效和安全性。总共有 333 名患者（EVR + rTAC，169 名；sTAC，164 名）被纳入 FAS。很大一部分患者在维持他克莫司谷水平方面不依从（EVR + rTAC，36.1%；sTAC，34.7%）。在第 12 个月时，EVR + rTAC 与 sTAC 相比，调整后的最小二乘平均 eGFR 在数值上更高（76.2 与 72.1 mL/minute/1.73 m²、差值：4.1 mL/min/1.73 m ²；P  = 0.097）。 在依从性组中注意到有利于 EVR + rTAC 的8.3 mL/分钟/1.73 m ² ( P = 0.03) 的显着差异。第 12 个月时复合疗效终点（7.7% 对 7.9%）和 tBPAR（7.1% 对 5.5%）的发生率以及治疗中出现的不良事件（AE）和严重 AE 的发生率在组间具有可比性。与 sTAC 治疗相比，停止 EVR + rTAC 治疗的患者比例较低（27.2% 对 34.1%）。在第 12 个月，早期使用依维莫司联合 rTAC 显示出与 sTAC 治疗相当的疗效、安全性和保存完好的肾功能。值得注意的是，依从性组的肾功能显着增强。