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肝移植术后手术耐受性相关因素:一项单中心回顾性研究

Factors associated with operational tolerance after liver transplantation: a single center retrospective study.

作者信息

Park Sunghae, Choi Gyu-Seong

机构信息

Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

出版信息

Korean J Transplant. 2023 Dec 31;37(4):286-292. doi: 10.4285/kjt.23.0066.

DOI:10.4285/kjt.23.0066
PMID:38153255
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10772272/
Abstract

BACKGROUND

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.

METHODS

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).

RESULTS

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.

CONCLUSIONS

These findings suggest that larger, healthier grafts are more conducive to inducing tolerance, and regulatory T cells are crucial in achieving tolerance.

摘要

背景

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。

方法

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。

结果

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。

结论

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9eb/10772272/c92afe396a23/kjt-37-4-286-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9eb/10772272/c92afe396a23/kjt-37-4-286-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9eb/10772272/c92afe396a23/kjt-37-4-286-f1.jpg

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本文引用的文献

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Regulatory T-Cell Therapy in Liver Transplantation and Chronic Liver Disease.调节性 T 细胞治疗肝移植和慢性肝病。
Front Immunol. 2021 Oct 14;12:719954. doi: 10.3389/fimmu.2021.719954. eCollection 2021.
2
Cell-Mediated Therapies to Facilitate Operational Tolerance in Liver Transplantation.细胞介导的治疗方法促进肝移植中的操作性耐受。
Int J Mol Sci. 2021 Apr 13;22(8):4016. doi: 10.3390/ijms22084016.
3
Strategies for Liver Transplantation Tolerance.肝移植耐受的策略。
Int J Mol Sci. 2021 Feb 24;22(5):2253. doi: 10.3390/ijms22052253.
4
Inducing Transient Mixed Chimerism for Allograft Survival Without Maintenance Immunosuppression With Combined Kidney and Bone Marrow Transplantation: Protocol Optimization.诱导混合嵌合体以实现同种异体移植物存活而无需联合肾和骨髓移植的维持性免疫抑制:方案优化。
Transplantation. 2020 Jul;104(7):1472-1482. doi: 10.1097/TP.0000000000003006.
5
Immune Dysfunction and Risk of Infection in Chronic Kidney Disease.慢性肾脏病患者的免疫功能障碍与感染风险。
Adv Chronic Kidney Dis. 2019 Jan;26(1):8-15. doi: 10.1053/j.ackd.2019.01.004.
6
Maintenance immunosuppression for adults undergoing liver transplantation: a network meta-analysis.肝移植成年受者的维持性免疫抑制:一项网状Meta分析。
Cochrane Database Syst Rev. 2017 Mar 31;3(3):CD011639. doi: 10.1002/14651858.CD011639.pub2.
7
Limitations of current liver transplant immunosuppressive regimens: renal considerations.当前肝移植免疫抑制方案的局限性:肾脏方面的考量
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