Liver Transplantation and Hepatology Unit, La Fe University Hospital, Valencia, and Instituto de Investigación Sanitaria, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.
Transplantation. 2020 Jun;104(6):1201-1209. doi: 10.1097/TP.0000000000002987.
There is an interest in understanding the association between early calcineurin inhibitors exposure post-liver transplantation (LT) and long-term outcomes. We aimed to analyze this association exploring median calcineurin inhibitor levels and intrapatient variability (IPV) in a multicenter, retrospective cohort.
Tacrolimus (Tac) and Cyclosporine (CsA) levels obtained during the first 15 days post-LT were collected. High immunosuppression (IS) was considered as a median of Tac, CsA blood trough levels 12 hours after drug administration, or blood levels 2 hours after drug administration higher than 10, 250, or 1200 ng/mL, respectively, or a peak of Tac >20 ng/mL. Optimal IS was defined as a median of Tac, CsA blood trough levels 12 hours after drug administration, or blood levels 2 hours after drug administration levels between 7 and 10, 150 and 250, or 800 and 1200 ng/mL. Low IS was defined as below the thresholds of optimal IS. IPV was estimated during the first 15 days post-LT.
The study included 432 patients with a median follow-up of 8.65 years. IS regimen was based on either Tac or CsA in 243 (56.3%) and 189 (43.8%), respectively. There were no differences in terms of graft loss among low versus optimal and high IS groups (P = 0.812 and P = 0.451) nor in high versus low IPV (P = 0.835). Only viral hepatitis and arterial hypertension were independently associated with higher graft loss (hazard ratio = 1.729, P = 0.029 and hazard ratio = 1.570, P = 0.021).
In contrast to what has previously been reported, no association was found between very early postoperative over IS or high IPV and long-term outcome measures following LT. Strategies aimed at reducing these long-term events should likely focus on other factors or on a different IS time window.
人们对理解肝移植（LT）后早期钙调神经磷酸酶抑制剂暴露与长期结果之间的关系很感兴趣。我们旨在通过多中心回顾性队列研究，分析探索中位钙调神经磷酸酶抑制剂水平和患者内变异（IPV）的相关性。
收集 LT 后第 15 天内获得的他克莫司（Tac）和环孢素（CsA）水平。高免疫抑制（IS）被定义为 Tac、CsA 血药谷浓度 12 小时后药物给药，或药物给药后 2 小时后血药浓度分别高于 10、250 或 1200ng/ml，或 Tac 峰浓度>20ng/ml。最佳 IS 定义为 Tac、CsA 血药谷浓度 12 小时后药物给药，或药物给药后 2 小时后血药浓度在 7 至 10、150 至 250 或 800 至 1200ng/ml 之间。低 IS 定义为低于最佳 IS 阈值。在 LT 后第 15 天内评估 IPV。
该研究纳入了 432 例患者，中位随访时间为 8.65 年。IS 方案分别基于 Tac 或 CsA 的患者分别为 243（56.3%）和 189（43.8%）。低 IS 组与最佳 IS 组和高 IS 组在移植物丢失方面无差异（P=0.812 和 P=0.451），高 IS 组与高 IPV 组也无差异（P=0.835）。只有病毒性肝炎和动脉高血压与更高的移植物丢失独立相关（风险比=1.729，P=0.029 和风险比=1.570，P=0.021）。
与之前的报道相反，LT 后非常早期的术后过度 IS 或高 IPV 与长期结果测量之间没有关联。旨在减少这些长期事件的策略可能应该集中在其他因素或不同的 IS 时间窗口上。
