Appenzeller-Herzog Christian, Hartleif Steffen, Vionnet Julien
University Medical Library, University of Basel, Basel, Switzerland.
University Hospital Tübingen, Pediatric Gastroenterology and Hepatology, Stuttgart, Germany.
Am J Transplant. 2021 Oct;21(10):3312-3323. doi: 10.1111/ajt.16585. Epub 2021 May 1.
Indefinite allograft acceptance after immunosuppression withdrawal (ISW), also known as operational tolerance (OT), can occur spontaneously after liver transplantation (LT), but reliable and reproducible prognosis of OT versus non-OT outcomes remains elusive. To prime this, systematic extraction of OT-predictive factors from the literature is crucial. We provide the first comprehensive identification and synthesis of clinical parameters and biomarkers predicting spontaneous OT in non-autoimmune/non-replicative viral LT recipients selected for ISW. We searched Embase, Medline, the Cochrane Central Register of Controlled Trials, clinicaltrials.gov, and the World Health Organization International Clinical Trials Registry Platform for articles, conference abstracts, and ongoing trials. We contacted principal investigators of stand-alone abstracts and ongoing trials for unpublished data and screened citations and references of eligible articles. Twenty-three articles reporting on 11 completed ISW studies, 13 abstracts, and five trial registry entries were included. Longer time between LT and ISW was the only clinical parameter that may increase the incidence of OT. Prognostic biomarkers conspicuously differed between pediatric and adult ISW candidates. These included allograft gene expression patterns and peripheral blood immune exhaustion markers for adults, and histological allograft scores for children. Our results will foster cross-validation efforts to facilitate safe and harmonized candidate selection for successful ISW.
免疫抑制撤除（ISW）后同种异体移植物长期存活，也称为操作性耐受（OT），可在肝移植（LT）后自发发生，但OT与非OT结局的可靠且可重复的预后仍然难以捉摸。为此，从文献中系统提取OT预测因素至关重要。我们首次全面识别并综合了在选择进行ISW的非自身免疫/非复制性病毒LT受者中预测自发OT的临床参数和生物标志物。我们在Embase、Medline、Cochrane对照试验中央注册库、clinicaltrials.gov和世界卫生组织国际临床试验注册平台中搜索文章、会议摘要和正在进行的试验。我们联系了独立摘要和正在进行试验的主要研究者以获取未发表的数据，并筛选了符合条件文章的参考文献。纳入了23篇报告11项已完成的ISW研究、13篇摘要和5项试验注册条目的文章。LT与ISW之间的时间间隔较长是唯一可能增加OT发生率的临床参数。儿科和成人ISW候选者的预后生物标志物明显不同。这些包括成人的同种异体移植基因表达模式和外周血免疫耗竭标志物，以及儿童的组织学同种异体移植评分。我们的结果将促进交叉验证工作，以方便为成功的ISW进行安全且统一的候选者选择。
