Park Sunghae, Choi Gyu-Seong
Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Korean J Transplant. 2023 Dec 31;37(4):286-292. doi: 10.4285/kjt.23.0066.
Liver transplantation has adverse effects from life-long immunosuppression that limit the improvement of long-term outcomes. Achieving clinical operational tolerance is a major goal in organ transplantation.
This study analyzed liver transplantation patients at a single institution from 1998 to 2020, excluding those who died within 1-year posttransplant. Operational tolerance was defined as normal liver function even after immunosuppressive drugs were discontinued. Propensity score matching was implemented at a 1:2 ratio for the tolerant group (TG) and the nontolerant group (NTG).
Out of 2,300 recipients, 99 achieved operational tolerance without rejection. No significant differences in sex or body mass index (BMI) were found between the TG and NTG. There was a significantly higher percentage of children in the TG (24.0%) than in the NTG (10.1%). The NTG had more living donor liver transplants. Among 2,054 adult recipients, no significant differences in age, sex, or BMI were found between the TG and the NTG. However, the rate of living donor liver transplantation was 40.3% (29/75) in the TG and 84.8% in the NTG (P<0.001). The propensity score-matched analysis showed higher chronic renal failure rates and a higher graft recipient weight ratio in the TG, along with shorter warm ischemic times during surgery. After immunosuppressant withdrawal, a significant increase in the ratio of CD4+CD25+ T cells to total CD4+ T cells was observed in the TG.
These findings suggest that larger, healthier grafts are more conducive to inducing tolerance, and regulatory T cells are crucial in achieving tolerance.
肝移植存在终身免疫抑制带来的不良反应,这限制了长期预后的改善。实现临床操作耐受是器官移植的一个主要目标。
本研究分析了1998年至2020年在单一机构接受肝移植的患者,排除移植后1年内死亡的患者。操作耐受定义为即使停用免疫抑制药物后肝功能仍正常。对耐受组(TG)和非耐受组(NTG)按1:2的比例实施倾向得分匹配。
在2300名受者中,99人实现了无排斥的操作耐受。TG组和NTG组在性别或体重指数(BMI)方面无显著差异。TG组儿童的比例(24.0%)显著高于NTG组(10.1%)。NTG组活体供肝移植更多。在2054名成年受者中,TG组和NTG组在年龄、性别或BMI方面无显著差异。然而,TG组活体供肝移植率为40.3%(29/75),NTG组为84.8%(P<0.001)。倾向得分匹配分析显示,TG组慢性肾衰竭发生率更高,移植物受者体重比更高,手术期间热缺血时间更短。停用免疫抑制剂后,TG组CD4+CD25+T细胞与总CD4+T细胞的比例显著增加。
这些发现表明,更大、更健康的移植物更有利于诱导耐受,调节性T细胞在实现耐受中至关重要。