Study on the tolerance induction after liver transplantation

肝移植术后耐受诱导的研究

• 批准号: 10470239
• 负责人: KAWASAKI Seiji
• 金额: $ 8.45万
• 依托单位: Shinshu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10470239/
• 关键词: Cytokine; Interleukin; TNF; Epstein-Barr virus; インターロイキン-2; インターフェロン-γ; TGF-B; リンパ球表面マーカー

It has been expected that living-related donor liver graft transplantation (LRLT) might have some immunological advantages over cadaveric transplantation. The objective of this study was to analyze a single center's experience with 110 LRLT in pediatric and adult patients with special reference to immunological response in the recipients.The medical records of 110 consecutive patients who underwent LRLT were reviewed. The relationship between pretransplant covariates and patient and graft survival was analyzed. Actuarial patient/graft survival rates were determined at 1, 3 and 5 years. The type and incidence of posttransplant complications including acute and chronic allograft rejection were analyzed. In addition, the perioperative profiles of serum cytokine levels as well as cytokine mRNA expression in the liver were investigated.The 1-, 3-, and 5-year actuarial patient and graft survival rates were 88%, 85%, and 85%, respectively. Log-rank test demonstrated that ABC-compatibility predicted patient survival rate, whereas patient age, underlying disease, patient's clinical status, donor-recipient relation, donor age and graft volume/standard liver volume ratio did not. Human leukocyte antigen matching was not the factor affecting the incidence of rejection. Interleukin-6, 8, 12, 15 levels in the serum were elevated in accordance with allograft rejection In the patients with Epstein-Barr virus related posttransplant lymphoproliferative disorder where the cessation of immunosuppressant is possible, serum interleukin-10 level was elevated.The control of Th1/Th2 cytokine balance as well as the blockade of costimulatory signaling are the keys to overcome immunological sequelae after liver transplantation.

人们预计，活体相关供体肝移植（LRLT）可能比尸体移植具有一些免疫学优势。本研究的目的是分析单个中心在儿童和成人患者中进行 110 例 LRLT 的经验，特别是受者的免疫反应。对 110 名连续接受 LRLT 的患者的医疗记录进行了审查。分析了移植前协变量与患者和移植物存活之间的关系。精算患者/移植物存活率在 1、3 和 5 年确定。分析急性和慢性同种异体移植排斥反应等移植后并发症的类型和发生率。此外，还研究了围手术期血清细胞因子水平以及肝脏细胞因子mRNA表达。精算患者和移植物的1年、3年和5年存活率分别为88%、85%和85%。对数秩检验表明，ABC 相容性可以预测患者的生存率，而患者年龄、基础疾病、患者的临床状态、供体-受者关系、供体年龄和移植物体积/标准肝脏体积比则不能预测。人类白细胞抗原匹配不是影响排斥反应发生的因素。血清中白细胞介素6、8、12、15水平随同种异体移植排斥而升高。在可以停止免疫抑制剂的EB病毒相关移植后淋巴增殖性疾病患者中，血清白细胞介素10水平升高。控制Th1/Th2细胞因子平衡以及阻断共刺激信号是克服的关键 肝移植后的免疫学后遗症。

项目成果

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Kawasaki S.: "Relationship between in vivo FK506 clearance and in vitro 13-demethylation activity in livingrelated liver transplantation"Transplantation. 66(8). 1089-1093 (1998)

Kawasaki S.：“活体相关肝移植中体内 FK506 清除率与体外 13-去甲基化活性之间的关系”移植。

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Kawasaki S.: "Relationship between in vivo FK 506 clearance and in vitro 13-demethylation activity living related liver transplantation"Transplantation. 66. 1089-1093 (1998)

Kawasaki S.：“体内 FK 506 清除率与体外 13-去甲基化活性活体相关肝移植之间的关系”移植。