Movahedi Zohreh, Holt Curtis D, Saab Sammy
Department of Gastroenterology, Pancreas Research Group, UCLA/VA Greater Los Angeles Healthcare System, USA.
Exp Clin Transplant. 2010 Jun;8(2):83-90.
Liver transplant has been accepted as a successful therapeutic option for patients with end-stage liver disease. Patient and graft survival has incrementally increased over the past 2 decades, mainly because of immunosuppressive regimens. However, the nonspecific nature of immunosuppressive agents is associated with an increased risk of development of opportunistic infections, renal impairment, metabolic derangements, neurotoxicity, de novo malignancies, and recurrence of the primary disease. Immunosuppressive regimen pharmacologic classes include calcineurin inhibitors, antimetabolites, mTOR inhibitors, steroids, and antibody-based therapies. These agents affect T-cell-dependent B-cell activation, and target different sites in the T-cell activation cascade by inhibiting T-cell activation or causing T-cell depletion. The goals of immunosuppression in solid-organ transplant are to prevent allograft rejection as well as optimize allograft function, prolong patient survival, and improve patient quality of life. Therefore, it is essential to carefully select the immunosuppressive regimen that will result in significant improvements in long-term liver transplant patients' survival and quality of life.
肝移植已被公认为是终末期肝病患者的一种成功治疗选择。在过去20年里,患者和移植物的存活率逐步提高,这主要归功于免疫抑制方案。然而,免疫抑制剂的非特异性本质与机会性感染、肾功能损害、代谢紊乱、神经毒性、新发恶性肿瘤以及原发性疾病复发风险的增加有关。免疫抑制方案的药理学类别包括钙调神经磷酸酶抑制剂、抗代谢物、mTOR抑制剂、类固醇和基于抗体的疗法。这些药物影响T细胞依赖性B细胞活化,并通过抑制T细胞活化或导致T细胞耗竭来靶向T细胞活化级联反应中的不同位点。实体器官移植中免疫抑制的目标是预防移植物排斥反应以及优化移植物功能、延长患者生存期并改善患者生活质量。因此,仔细选择能显著提高长期肝移植患者生存率和生活质量的免疫抑制方案至关重要。