Induction and elucidation of operational tolerance in pediatric liver transplantation
| Project/Area Number |
17K10523
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Saitama Children's Medical Center (2019)
Jichi Medical University (2017-2018) |
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Principal Investigator |
Mizuta Koichi 埼玉県立小児医療センター (臨床研究部), 移植外科, センター長 (00313148)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 小児肝移植 / Operational tolerance / 免疫抑制薬離脱 / 免疫寛容 / キメリズム / 免疫抑制剤離脱 / 肝移植 / 小児 |
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| Outline of Final Research Achievements |
The objective of this study was to evaluate the possibility of immunosuppression (IS) withdrawal and to identify parameters associated with IS withdrawal in pediatric living donor liver transplantation (LDLT). IS withdrawal trial was attempted in 46 patients who met entry criteria. Twenty-eight of the patients (61%) achieved a complete IS withdrawal. Eleven patients (24%) discontinued CNI weaning due to the appearance of liver dysfunction. The rate of serum antinuclear antibody (ANA) positivity in patients who discontinued CNI weaning was significantly higher than that in the other patients. Although 5 of 28 IS-free patients restarted IS based on pathological findings, these findings were improved following the resumption of IS therapy. In pediatric LDLT, if patients are appropriately selected and a IS withdrawal protocol is attempted under appropriate monitoring, there is a possibility of inducing operational tolerance. ANA is considered to be a risk factor for CNI weaning.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、免疫寛容を獲得した小児肝移植後患者においては、長期間免疫寛容の状態を維持できることが証明された。肝移植後の長期フォローアップには、自己抗体や線維化マーカーの測定、肝生検による病理学的評価が重要であり、移植後管理の標準化に有用な情報である。安全に免疫抑制剤の減量・離脱ができれば、免疫抑制剤の長期投与によって生じる患者の肉体的・精神的・経済的負担を軽減させるだけでなく、本邦における医療費削減にも大きく貢献するものと期待される。また、本研究成果は、今後日本でも展開されるであろう免疫寛容誘導の多施設共同のランダム化比較試験や、免疫抑制剤減量のガイドラインの作成に寄与できる結果である。
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Report
(4 results)
Research Products
(3 results)
