Hepatobiliary and Liver Transplantation Unit, University of Padova, Padova, Italy.
Department of General and Visceral Surgery, Frankfurt University Hospital and Clinics, Frankfurt, , Germany.
Transplant Rev (Orlando). 2018 Jul;32(3):142-150. doi: 10.1016/j.trre.2018.04.001. Epub 2018 Apr 13.
Changes in recipient and donor characteristics are redefining the role of induction in liver transplant recipients. Older recipients are more common, with greater concomitant comorbidity. Moderate or severe renal dysfunction is now estimated to affect 40% of liver transplant recipients. Donors are also becoming older, and other factors such as more frequent non-alcoholic fatty liver disease (NAFLD) compromise the quality of some grafts. Rejection rates are now relatively low (~10%) but some patients have a markedly increased risk such as younger recipients and those undergoing re-transplantation. Induction immunosuppression is associated with a significant reduction in rejection risk but due to various factors universal induction is not justified. Steroid-free therapy without induction increases the risk of biopsy-proven acute rejection (BPAR) but randomized trials have shown that induction with an interleukin-2 antagonist receptor (IL-2RA) agent or with rabbit antithymocyte globulin (rATG) maintains immunosuppressive efficacy in steroid-free regimens. Delayed calcineurin inhibitor (CNI) initiation (e.g. to days 4-5 post-transplant) can prevent deterioration of renal function during the first year post-transplant, but requires induction with an IL-2RA agent or rATG to maintain early immunosuppressive efficacy. IL-2RA induction may be inadequate to ensure a low risk of rejection in a steroid-free regimen combined with delayed tacrolimus. Randomized trials of CNI withdrawal at month 1 post-transplant have only achieved an acceptable rate of BPAR when induction is administered. In terms of safety, an increased rate of infection does not seem to be a concern. The most recent large-scale analyses have not indicated any evidence for an increased risk of malignancy, or specifically post-transplant lymphoproliferative disease. In summary, the place of induction in the management of liver transplant patients is becoming established. Selective use in high-risk individuals to avoid graft rejection is still relevant, but the key rationale for induction is to facilitate steroid-sparing and CNI-sparing regimens to reduce long-term complications.
受者和供者特征的变化正在重新定义肝移植受者中诱导治疗的作用。年龄较大的受者更为常见，合并症也更多。中度或重度肾功能不全现在估计影响 40%的肝移植受者。供者也越来越老，非酒精性脂肪性肝病（NAFLD）等其他因素使一些移植物的质量受损。现在排斥反应的发生率相对较低（~10%），但有些患者的风险明显增加，如年轻受者和再次接受移植的患者。诱导免疫抑制与降低排斥反应风险显著相关，但由于各种因素，并非所有患者都需要诱导免疫抑制。无诱导的无激素治疗会增加活检证实的急性排斥反应（BPAR）的风险，但随机试验表明，使用白细胞介素-2 拮抗剂受体（IL-2RA）或兔抗胸腺细胞球蛋白（rATG）进行诱导，可在无激素方案中维持免疫抑制疗效。延迟钙调神经磷酸酶抑制剂（CNI）的起始（例如在移植后第 4-5 天）可以防止移植后第一年肾功能恶化，但需要使用 IL-2RA 或 rATG 进行诱导以维持早期免疫抑制疗效。IL-2RA 诱导可能不足以确保在与延迟他克莫司联合的无激素方案中排斥反应的低风险。在移植后 1 个月时进行 CNI 停药的随机试验只有在诱导治疗时才能达到可接受的 BPAR 发生率。就安全性而言，感染率增加似乎不是一个问题。最近的大规模分析并未表明在诱导治疗时存在增加恶性肿瘤风险或特定的移植后淋巴组织增生性疾病风险的证据。总之，诱导在肝移植患者管理中的地位已经确立。选择性地用于高危人群以避免移植物排斥反应仍然相关，但诱导的关键理由是促进激素和 CNI 节约方案以减少长期并发症。
