免疫抑制和肝移植  

Immunosuppression and Liver Transplantation

作　　者：Jan Lerut Samuele Iesari 

机构地区：[1]Institut de Recherche Expérimentale et Clinique,Universitécatholique de Louvain,Brussels 1200,Belgium [2]General Surgery and Kidney Transplantation,Fondazione IRCCS Ca’Granda Ospedale Maggiore Policlinico,Milan 20122,Italy

出　　处：《Engineering》2023年第2期175-187,M0007,共14页工程（英文）

摘　　要：完美的手术技术和充分的免疫抑制是确保最佳移植物和患者存活的关键。不同药物的可用性导致了一些通常由行业驱动的不同类型的临床试验,以发现理想的免疫抑制方案。然而,大量且概念不同的研究设计未能明确定义最佳免疫抑制方案。基于钙调神经磷酸酶抑制剂他克莫司、抗代谢药物霉酚酸酯或硫唑嘌呤和短期类固醇(除了可能的诱导外)为基础的三联免疫抑制方案仍然是目前公认的肝移植标准免疫抑制方案。然而,鉴于排斥定义的变化、免疫抑制负荷的定制以及由于慢性免疫抑制引起的长期副作用,未来的试验最好包括一个以上的终点,而不是急性T细胞介导的急性排斥(a-TCMR)或肾衰竭。相反,需要一个涵盖患者和移植物存活率以及急性和慢性排斥反应发生率的综合终点。这些免疫现象应根据一系列长期的生物学和组织学随访进行检查。临床相关a-TCMR的诊断和治疗应基于综合生物学、免疫学和组织病理学发现。这两个要素对于朝着更谨慎的免疫抑制处理和有利于临床操作耐受性的方向发展至关重要。Perfect surgical techniques and adequate immunosuppression are key to ensuring optimal graft and patient survival.The availability of different drugs has led to several,often industry-driven,heterogeneous clinical trials to discover an ideal immunosuppressive regimen.However,the considerable and conceptually diverse study designs have failed to afford a clear definition of the optimal immunosuppression regimen.The triple-drug immunosuppressive regimen,based on the calcineurin inhibitor tacrolimus,antimetabolites mofetil mycophenolate or azathioprine,and short-term steroids-beyond possible induction-remains the currently accepted standard immunosuppression in liver transplantation.However,this regimen needs to be challenged in light of the changing definitions of rejection,customization of the immunosuppressive load,and long-term side effects due to chronic immunosuppression.Future trials should preferably include more than a single endpoint rather than acute T-cell-mediated acute rejection(a-TCMR)or kidney failure.Conversely,a comprehensive endpoint that covers patient and graft survival rates and the incidence of both acute and chronic rejection is warranted.These immune phenomena should be examined in light of serial long-term biological and histological follow-up.The diagnosis and treatment of clinically relevant a-TCMR should be based on integrated biological,immunological,and histopathological findings.Both elements are critical to progress toward more prudent immunosuppression handling and favor clinical operational tolerance.

关 键 词：免疫抑制方案 抗代谢药物 急性排斥 移植物 硫唑嘌呤 组织病理学 临床试验 肝移植 

分 类 号：R657.3[医药卫生—外科学]