Asan Medical Center, Ulsan University College of Medicine, Seoul, Republic of Korea.
China Medical University Hospital, Taichung, Taiwan.
Transplantation. 2021 Jul 1;105(7):1564-1575. doi: 10.1097/TP.0000000000003394.
Data from 2 randomized liver transplant trials (N = 772; H2304 [deceased donor, n = 488], H2307 [living donor, n = 284]) were pooled to further evaluate the efficacy and safety of everolimus with reduced tacrolimus (EVR + rTAC) versus standard tacrolimus (sTAC) regimen at month 24.
EVR + rTAC was comparable to sTAC for composite efficacy failure of treated biopsy-proven acute rejection, graft loss, or death (9.8% versus 10.8%; difference, -1.0%; 95% confidence interval, -5.4 to 3.4; P = 0.641) at month 24. EVR + rTAC was superior to sTAC for the mean change in estimated glomerular filtration rate (eGFR) from randomization to month 24 (-8.37 versus -13.40 mL/min/1.73 m2; P = 0.001). A subanalysis of renal function by chronic kidney disease (CKD) stage at randomization showed significantly lower decline in eGFR from randomization to month 24 for patients with CKD stage 1/2 (eGFR ≥ 60 mL/min/1.73 m2) in EVR + rTAC group versus sTAC (-12.82 versus -17.67 mL/min/1.73 m2, P = 0.009). In patients transplanted for hepatocellular carcinoma (HCC) beyond Milan criteria, HCC recurrence was numerically lower although not statistically significant with EVR + rTAC versus sTAC group (5.9% [1 of 17] versus 23.1% [6 of 26], P = 0.215), while comparable in patients within Milan criteria (2.9% [3 of 102] versus 2.1% [2 of 96], P = 1.000), irrespective of pretransplant alpha-fetoprotein levels.
EVR + rTAC versus sTAC showed comparable efficacy and safety with significantly better renal function, particularly in patients with normal/mildly decreased renal function (CKD stage 1/2) at randomization and a trend toward lower HCC recurrence in patients transplanted with HCC beyond Milan at month 24. Further long-term data would be required to confirm these results.
对来自 2 项随机肝移植试验（N=772；H2304[已故供体，n=488]，H2307[活体供体，n=284]）的数据进行汇总，以进一步评估依维莫司联合低剂量他克莫司（EVR+rTAC）与标准他克莫司（sTAC）方案在 24 个月时的疗效和安全性。
EVR+rTAC 在治疗活检证实的急性排斥反应、移植物丢失或死亡的复合疗效失败方面与 sTAC 相当（9.8%与 10.8%；差异，-1.0%；95%置信区间，-5.4 至 3.4；P=0.641）。EVR+rTAC 在随机化至 24 个月时估计肾小球滤过率（eGFR）的平均变化方面优于 sTAC（-8.37 与-13.40 mL/min/1.73 m2；P=0.001）。按随机化时慢性肾脏病（CKD）分期的肾功能亚组分析显示，在 CKD 分期 1/2（eGFR≥60 mL/min/1.73 m2）的患者中，EVR+rTAC 组较 sTAC 组从随机化到 24 个月时 eGFR 的下降幅度显著更低（-12.82 与-17.67 mL/min/1.73 m2，P=0.009）。在米兰标准以外接受肝移植的肝细胞癌（HCC）患者中，EVR+rTAC 组 HCC 复发率虽然略低于 sTAC 组，但无统计学意义（5.9%[17 例中的 1 例]与 23.1%[26 例中的 6 例]，P=0.215），而在米兰标准以内的患者中两组相似（2.9%[102 例中的 3 例]与 2.1%[96 例中的 2 例]，P=1.000），且与移植前甲胎蛋白水平无关。
EVR+rTAC 与 sTAC 相比具有相当的疗效和安全性，且肾功能明显更好，特别是在随机化时肾功能正常/轻度下降（CKD 分期 1/2）的患者中，并且在 24 个月时米兰标准以外接受 HCC 移植的患者中 HCC 复发率呈下降趋势。需要进一步的长期数据来证实这些结果。
