Early elimination of tacrolimus in favor of everolimus can improve renal function in liver transplant recipients. However, as this approach increases the risk of acute rejection, it may benefit from predictive biomarkers guiding weaning. We enrolled 20 recipients on stable tacrolimus + everolimus to undergo tacrolimus withdrawal early post-liver transplant. Blood samples were collected at month 3 (withdrawal initiation), 4 (withdrawal completion), 4.5 and 6 (both everolimus alone). 15 patients did not reject and 5 had mild rejection responding to tacrolimus resumption. Before tacrolimus withdrawal, eventual rejecters had higher percentages of CD56⁺ NK cells and CD19⁺CD27⁺CD24⁺ memory B cells, and lower levels of T cells expressing the exhaustion marker PD-1. Over time, memory B cells, Ki-67⁺CD3⁺ (proliferating) cells and CD4⁺CD127^-CD25^HIGH FOXP3⁺ Tregs increased in rejecters. Tregs also increased in non-rejecters over time. The number of differentially expressed genes progressively increased in rejecters, particularly in mTOR, Eukaryotic Initiation Factor 2, and Neuroinflammation signaling pathways. There was no difference in anti-HLA antibodies between the groups. In summary, blood mononuclear cell and gene expression may predict successful vs. failed early tacrolimus withdrawal in liver transplant recipients. While needing validation, these preliminary findings highlight the potential for cellular and molecular biomarkers to guide decision-making during tacrolimus weaning.

早期消除他克莫司以支持依维莫司可改善肝移植受者的肾功能。然而，由于这种方法会增加急性排斥反应的风险，因此它可能会受益于指导撤机的预测性生物标志物。我们招募了 20 名接受稳定他克莫司 + 依维莫司治疗的受者，以在肝移植后早期停用他克莫司。在第 3 个月（开始戒断）、第 4 个月（完成戒断）、第 4.5 个月和第 6 个月（均单独使用依维莫司）收集血样。他克莫司恢复治疗后，15 名患者未出现排斥反应，5 名患者出现轻度排斥反应。在他克莫司停药前，最终排斥者的 CD56 ⁺ NK 细胞和 CD19 ⁺ CD27 ⁺ CD24 ^{+ 的}百分比更高记忆 B 细胞，以及表达耗竭标志物 PD-1 的 T 细胞水平较低。随着时间的推移，记忆B细胞，Ki-67的⁺ CD3 ⁺（增殖）细胞和CD4 ⁺ CD127 ^- CD25 ^HIGH FOXP3 ⁺拒绝者中的 Tregs 增加。随着时间的推移，非排斥者的 Tregs 也增加。差异表达基因的数量在排斥基因中逐渐增加，尤其是在 mTOR、真核启动因子 2 和神经炎症信号通路中。各组之间的抗 HLA 抗体没有差异。总之，血液单核细胞和基因表达可以预测肝移植受者早期他克莫司戒断成功与失败。虽然需要验证，但这些初步发现强调了细胞和分子生物标志物在他克莫司断奶期间指导决策的潜力。