Clinical research progress of drug-reducing regimen for immunosuppressants after liver transplantation
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摘要: 肝移植已成为治疗终末期肝病的主要手段，然而术后的肿瘤复发、代谢性疾病、肾功能不全等严重影响了受体的生活质量及长期生存率。这些疾病的发生发展与免疫抑制剂的方案有着密切的关系。本文主要针对肾上腺皮质激素（激素）和钙神经蛋白抑制剂（CNI）这两类药物在原发性肝脏恶性肿瘤术后、肝移植术后预防代谢性疾病以及预防肾损伤的减药方案及联合应用其他免疫抑制剂三方面进行综述，以期对术后免疫抑制剂管理提供参考。
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表 1 免疫抑制剂对肝移植术后代谢性疾病的不良影响
Table 1. Adverse effects of immunosuppressive agents on metabolic diseases after liver transplantation
肝移植术后代谢性疾病 糖皮质激素 他克莫司 西罗莫司 MMF 糖尿病 +++ ++ － － 高血压 + ++ + － 高脂血症 + + +++ － +代表不良影响强度，－代表未发现有不良影响 
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表 2 肝移植受体预防代谢性疾病的免疫抑制剂推荐应用方案
Table 2. Recommended application project of immunosuppressive agents in the prevention of metabolic diseases in liver transplant recipients
肝移植术后代谢性疾病 免疫抑制方案 糖尿病 他克莫司（减量）a +MMFb 高血压 他克莫司（减量）a +MMFb（+糖皮质激素快速撤除）c 高脂血症 他克莫司（减量）a +MMFb（+糖皮质激素快速撤除）c a他克莫司于肝移植术后2 d开始服药，起始量为1~2 mg，每日2次，根据肝功能调整药物剂量，与其他免疫抑制剂联用时，可适当减量。b若患者肝移植术后白细胞水平正常，可于术后7 d开始服用MMF，起始剂量为0.25 g，每日2次，若患者未出现明显骨髓抑制、胃肠道反应等不良反应，可酌情加量，并适当减少他克莫司剂量；若白细胞水平比较低，待稳定到正常水平后，根据移植器官功能情况再考虑添加。c肝移植术后1 d 60 mg，每日4次静脉滴注，此后每日减量10 mg，术后1周改为口服20 mg（每日1次），每周递减5 mg，直至停药
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表 3 预防肝移植受体肾损伤的免疫抑制剂推荐应用方案
Table 3. Recommended application project of immunosuppressive agents in the prevention of renal injury in liver transplant recipients
肝移植术后肾损伤 免疫抑制方案 AKI 他克莫司（减量）a +MMFb 他克莫司（减量）a +依维莫司c 他克莫司（减量）a +MMFb +IL-2受体拮抗剂d CKD 他克莫司（减量）a +MMFb 他克莫司（减量）a +依维莫司c a他克莫司于肝移植术后2 d开始服药，起始量为1~2 mg，每日2次，根据肝功能调整药物剂量，与其他免疫抑制药联用时，可适当减量。b若患者肝移植术后白细胞水平正常，可于术后第1周开始服用MMF，起始剂量为0.25 g，每日2次，若患者未出现明显骨髓抑制、胃肠道反应等不良反应，可酌情加量，并适当减少他克莫司剂量；若白细胞水平较低，待稳定到正常水平后，根据移植器官功能情况再考虑添加。c依维莫司于肝移植术后1个月开始服药，起始剂量为1 mg，每日2次，目标血药谷浓度调整至3~8 ng/mL。d肝移植术后1、4 d巴利昔单抗20 mg静脉滴注
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