Risk factors of complications after transplantation and pathology of chronic antibody-mediated rejection in pediatric liver transplantation

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08756
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Keio University (2019); National Center for Child Health and Development (2017-2018)
• Principal Investigator: Irie Rie 慶應義塾大学, 医学部(信濃町), 特任講師 (00365230)
• Co-Investigator(Kenkyū-buntansha): 中澤 温子 国立研究開発法人国立成育医療研究センター, 病理診断部, (非)研究員 (90227736)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 小児肝移植 / 拒絶 / 慢性抗体関連拒絶 / 抗ドナー抗体

Outline of Final Research Achievements

We found relationship between complications after pediatric liver transplantation such as rejection, liver dysfunction and original disease. Recipients of etiology-unknown acute liver failure tended to present steroid-resistant rejection which showed veno-occlusive like change, and percentage of graft failure was high, Recipients with metabolic disorders tended to present diffuse macrovesicular steatosis soon after liver transplantation, however steatosis was transient, and frequency of rejection was low.
We examined liver biopsy specimens of recipients under 18-year old who had positive results of donor-specific antibody (DSA) and were followed-up over 5 years after liver transplantation. Cases which had positive-DSA and met the diagnostic criteria of chronic antibody-mediated rejection by Banff Working Group showed progression of liver fibrosis compared with cases which did not meet the diagnostic criteria.

Free Research Field

人体病理

Academic Significance and Societal Importance of the Research Achievements

原疾患と移植後合併症の関連性を明らかにすることは、移植が成功しグラフトが生着すれば、50年以上の生命予後が十分に期待出来る小児症例におけるグラフト長期予後の更なる改善につながる。グラフト不全から再移植が必要となった際の選択肢が非常に厳しく限られている本邦において、移植後急性ならびに慢性の肝障害の病因を解明することは適切な治療法の確立とグラフト不全・再移植を回避することに繋がり生体肝移植主体の我が国における移植医療の発展に寄与できる結果を得られたと考える。