Liver Transplant Program, University of Pisa Medical School Hospital, Pisa, Italy; Department of Surgical, Medical, Biochemical Pathology and Intensive Care, University of Pisa, Italy.
Gastroenterology, Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy.
Transplant Rev (Orlando). 2024 Jan;38(1):100817. doi: 10.1016/j.trre.2023.100817. Epub 2023 Dec 16.
Older liver transplant recipients have a lower risk of acute rejection than younger patients (9% for patients aged ≥65 years versus 23% for those aged 18-34 years) and are more vulnerable to immunosuppression-related complications. The number of liver transplant recipients ≥65 years has risen to 22% in Europe and the US, but limited information is available on the optimal immunosuppressive regimen for these patients. In this review, we discuss the appropriate management of immunosuppressive agents in older adults to minimize adverse events while avoiding acute rejection. The way the body processes drugs greatly depends on age. In the case of calcineurin inhibitor drugs, aging reduces hepatic metabolism, leading to changes in their pharmacokinetics. Corticosteroids also show decreased clearance as the patient ages. In severe cases of hypoalbuminemia, dose adjustment of mycophenolate acid derivatives may be necessary. However, the pharmacokinetic profiles of the mammalian target of rapamycin inhibitors, basiliximab, and rabbit anti-thymocyte globulin remain unaffected by age. Furthermore, age-related frailty may impact drug metabolism and require tailored interventions and closer follow-up. Although there is limited research, elderly liver transplant recipients require less immunosuppression with double or triple-agent regimens, lower exposure to calcineurin inhibitors, and a shorter course of corticosteroids. The usage of mammalian target of rapamycin inhibitors in older transplant populations has not been specifically investigated, and thus their usage should align with indications for younger patient groups.
老年肝移植受者发生急性排斥反应的风险低于年轻受者（≥65 岁患者为 9%，18-34 岁患者为 23%），并且更容易发生与免疫抑制相关的并发症。≥65 岁的肝移植受者数量在欧洲和美国已上升至 22%，但针对这些患者的最佳免疫抑制方案的相关信息有限。在这篇综述中，我们讨论了老年患者中免疫抑制剂的合理管理，以尽量减少不良反应的同时避免急性排斥反应。药物在体内的代谢方式在很大程度上取决于年龄。对于钙调神经磷酸酶抑制剂，随着年龄的增长，肝脏代谢减少，导致其药代动力学发生变化。随着患者年龄的增长，皮质类固醇的清除率也会降低。在严重低白蛋白血症的情况下，可能需要调整霉酚酸酯衍生物的剂量。然而，雷帕霉素抑制剂、巴利昔单抗和兔抗胸腺细胞球蛋白的药代动力学特征不受年龄影响。此外，与年龄相关的虚弱可能会影响药物代谢，需要进行针对性干预和更密切的随访。尽管研究有限，但老年肝移植受者需要较少的免疫抑制药物，包括二联或三联方案、较低的钙调神经磷酸酶抑制剂暴露和较短疗程的皮质类固醇。雷帕霉素抑制剂在老年移植人群中的使用尚未得到专门研究，因此其使用应与年轻患者群体的适应证保持一致。
