肝移植临床可操作性耐受的研究现状及展望

长期免疫抑制治疗可增加肝移植受者感染性疾病和癌症的发生率和病死率，且现今免疫抑制治疗无法完全阻止和延缓慢性移植物排斥反应的发生。临床可操作性耐受（COT）是指不接受免疫抑制治疗而移植物长期存活，无有害的免疫应答证据且对肿瘤和感染有正常的免疫反应，被认为是避免移植物排斥反应发生的终极方案。20％～30％的肝移植受者在撤除免疫抑制剂后可产生自发性耐受，某些细胞和分子标志物被证实与肝移植受者免疫耐受状态有关。目前有研究表明嵌合体、诱导免疫调节细胞等方法可以诱导形成免疫耐受，但总体来说，肝移植COT的相关研究还处于起步阶段。本文就肝移植COT的临床证据、免疫监视、生物标志物和可能诱导耐受的策略等作一综述，以期为后续研究提供思路。

Status quo and prospect of studies about clinical operational tolerance of liver transplantation

Long-term immunosuppressive therapy of liver transplant recipients increases the incidence and mortality rate of infections and cancers, and the immune suppression can not completely prevent and delay chronic graft rejection. Clinical operational tolerance means long-term survival of the graft without immunosuppressive therapy, no harmful immune response and evidence, and even normal immune response to tumor and infection, which is considered to be the ultimate solution to avoid graft rejection. About 20% to 30% of liver transplant recipients produced spontaneous operational tolerance when immunosuppression was withdrawn. Some of cellular and molecular biomarkem were confirmed related to the immune tolerance state after liver transplantation. In addition, chimera and induction of immune regulating cell can induce immune tolerance state. Overall, the clinical feasibility research on operational tolerance of liver transplantation is still at its initial stage. This article reviewed the development of clinical operational tolerance in terms of clinical evidence, immune surveillance, biomarkers, and potential strategies.