Immunosuppression can be withdrawn from selected liver transplant recipients, although robust clinical predictors of tolerance remain elusive. The Immune Tolerance Network ITN056ST study (OPTIMAL; NCT02533180) assessed clinical outcomes and mechanistic correlates of phased immunosuppression withdrawal (ISW) in nonautoimmune, nonviral adult liver transplant recipients. Enrolled subjects were ≥3 years posttransplant with minimal/absent inflammation or fibrosis on a screening liver biopsy. The primary end point was operational tolerance at 52 weeks following complete ISW. Of 61 subjects who initiated ISW, 34 failed during ISW and 10 restarted immunosuppression after completing ISW due to clinically manifest acute rejection. Only 10 of 17 clinically stable subjects remaining off immunosuppression at 1 year were ultimately deemed tolerant by biopsy. There were no cases of chronic rejection or graft loss; 28.3% developed de novo donor-specific antibody during ISW, which persisted in 11.3%. The majority of subjects (78.6%), including those who experienced rejection, ended the study on same or less calcineurin inhibitor than at baseline. A minority (16.4%) of histologically and clinically stable long-term adult liver transplant recipients can successfully discontinue and remain off immunosuppression. Increased frequency of donor-specific T cell senescence, C4d deposition, and higher density of immune synapses on the screening liver biopsy emerged as potential candidate biomarkers for operational tolerance.

中文翻译：

---

供体特异性免疫衰老作为成人肝移植术后手术耐受性的候选生物标志物：一项前瞻性、多中心队列研究的结果


可以从选定的肝移植受者中撤回免疫抑制，但耐受性的稳健临床预测因子仍然难以捉摸。免疫耐受网络 ITN056ST 研究 （OPTIMAL;NCT02533180） 评估了非自身免疫、非病毒性成人肝移植受者分阶段免疫抑制戒断 （ISW） 的临床结果和机制相关性。入组受试者移植后 ≥3 年，筛查肝活检显示轻微/无炎症或纤维化。主要终点是完成 ISW 后 52 周的手术耐受性。在启动 ISW 的 61 名受试者中，34 名在 ISW 期间失败，10 名在完成 ISW 后由于临床表现的急性排斥反应而重新开始免疫抑制。在 1 年时仍未接受免疫抑制的 17 名临床稳定的受试者中，只有 10 名最终通过活检被认为耐受。没有慢性排斥反应或移植物丢失的病例;28.3% 的患者在 ISW 期间产生了从头供体特异性抗体，其中 11.3% 持续存在。大多数受试者 （78.6%），包括那些经历过排斥反应的受试者，以与基线相同或更少的钙调神经磷酸酶抑制剂结束研究。少数 （16.4%） 组织学和临床稳定的长期成人肝移植受者可以成功停止免疫抑制并保持状态。筛查肝活检中供体特异性 T 细胞衰老、C4d 沉积和免疫突触密度增加的频率增加成为手术耐受性的潜在候选生物标志物。