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

Research Project

Project/Area Number 17K08756
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Human pathology
Research InstitutionKeio 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
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords小児肝移植 / 拒絶 / 慢性抗体関連拒絶 / 抗ドナー抗体 / 慢性拒絶 / 肝移植 / 小児 / 急性細胞性拒絶 / 抗体関連拒絶 / グラフト不全
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.

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。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (22 results)

All 2020 2019 2018 2017

All Journal Article (9 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 9 results,  Open Access: 1 results) Presentation (13 results) (of which Int'l Joint Research: 4 results,  Invited: 1 results)

  • [Journal Article] Living donor liver transplantation for congenital hepatic fibrosis in children2020

    • Author(s)
      Irie R, Nakazawa A, Sakamoto S, Takeda M, Yanagi Y, Shimizu S, Uchida H, Fukuda A, Miyazaki O, Nosaka S, Kasahara M.
    • Journal Title

      Pathology International

      Volume: 70 Issue: 6 Pages: 348-354

    • DOI

      10.1111/pin.12917

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Etiology of liver dysfunction after liver transplantation in children with metabolic disorders.2020

    • Author(s)
      Irie R, Nakazawa A, Sakamoto S, Takeda M, Yanagi Y, Shimizu S, Uchida H, Fukuda A, Horikawa R, Kasahara M.
    • Journal Title

      Hepatology Research

      Volume: 50 Issue: 5 Pages: 635-642

    • DOI

      10.1111/hepr.13487

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Longterm Outcomes of Living Donor Liver Transplantation for Glycogen Storage Disease Type 1b.2020

    • Author(s)
      Shimizu S, Sakamoto S, Horikawa R, Fukuda A, Uchida H, Takeda M, Yanagi Y, Irie R, Yoshioka T, Kasahara M.
    • Journal Title

      Liver Transplantation

      Volume: 26 Issue: 1 Pages: 57-67

    • DOI

      10.1002/lt.25649

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Histologiccal changes of the intestinal mucosa in complications following a living donor liver transplantation for progressive familial intrahepatic cholestasis type12018

    • Author(s)
      Stephanie M, Irie R, Sasaki K, Hirata Y, Narumoto S, Fukuda A, Sakamoto S, Arai K, Yoshioka T, Kasahara M
    • Journal Title

      Pathology International

      Volume: 68 Issue: 9 Pages: 536-537

    • DOI

      10.1111/pin.12686

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Surgical treatment strategy for advanced hepatoblastoma: Resection versus transplantation2018

    • Author(s)
      Uchida Hajime、Sakamoto Seisuke、Sasaki Kengo、Takeda Masahiro、Hirata Yoshihiro、Fukuda Akinari、Hishiki Tomoro、Irie Rie、Nakazawa Atsuko、Miyazaki Osamu、Nosaka Shunsuke、Kasahara Mureo
    • Journal Title

      Pediatric Blood & Cancer

      Volume: 65 Issue: 12

    • DOI

      10.1002/pbc.27383

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] ABO-incompatible liver transplantation for children under 2?years of age: A case report and a single-center review2018

    • Author(s)
      Narumoto Soichi、Sakamoto Seisuke、Sasaki Kengo、Hirata Yoshihiro、Fukuda Akinari、Uchiyama Toru、Irie Rie、Yoshioka Takako、Kasahara Mureo
    • Journal Title

      Pediatric Transplantation

      Volume: 23 Issue: 1

    • DOI

      10.1111/petr.13308

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A severely cholestatic liver graft can be successfully used in deceased donor liver transplantation2017

    • Author(s)
      Sakamoto Seisuke、Sasaki Kengo、Uchida Hajime、Narumoto Soichi、Kitajima Toshihiro、Irie Rie、Fukuda Akinari、Yoshioka Takako、Kasahara Mureo
    • Journal Title

      Hepatology Research

      Volume: 48 Issue: 3

    • DOI

      10.1111/hepr.12968

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Necrotizing enterocolitis in the setting of milk allergy after pediatric living donor liver transplantation2017

    • Author(s)
      Narumoto Soichi、Sakamoto Seisuke、Uchida Hajime、Sasaki Kengo、Shigeta Takanobu、Fukuda Akinari、Nosaka Shunsuke、Irie Rie、Yoshioka Takako、Kasahara Mureo
    • Journal Title

      Pediatric Transplantation

      Volume: 22 Issue: 1

    • DOI

      10.1111/petr.13096

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Free cholesterol accumulation in liver sinusoidal endothelial cells exacerbates acetaminophen hepatotoxicity via TLR9 signaling2017

    • Author(s)
      Teratani Toshiaki、Tomita Kengo、Suzuki Takahiro、Furuhashi Hirotaka、Irie Rie、Hida Shigeaki、Okada Yoshikiyo、Kurihara Chie、Ebinuma Hirotoshi、Nakamoto Nobuhiro、Saito Hidetsugu、Hibi Toshifumi、Miura Soichiro、Hokari Ryota、Kanai Takanori
    • Journal Title

      Journal of Hepatology

      Volume: 67 Issue: 4 Pages: 780-790

    • DOI

      10.1016/j.jhep.2017.05.020

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Etiology of liver dysfuntion after transplantation in hildren with metaboli disorders2019

    • Author(s)
      Rie Irie, Atsuko Nakazawa, Akinari Fukuda, Seisuke Sakamoto, Mureo Kasahara
    • Organizer
      The 2019 Joint International Congress of ILTS, ELITA & LICAGE
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 乳幼児期に肝不全で発症する診断困難例における病理医の役割2019

    • Author(s)
      入江理恵、中澤温子、笠原群生
    • Organizer
      第108回日本病理学会総会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 代謝性疾患に対する肝移植直後に生ずる肝機能障害の組織学的検討2019

    • Author(s)
      入江理恵、中澤温子、中野雅之、笠原群生、義岡孝子
    • Organizer
      第108回日本病理学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 小児肝移植後長期経過症例におけるグラフト肝障害と抗ドナー抗体の関連2019

    • Author(s)
      入江理恵、中澤温子、武田昌寛、柳佑典、清水誠一、内田孟、福田晃也、阪本靖介、笠原群生
    • Organizer
      第55回日本移植学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 小児肝移植後長期経過例におけるグラフト肝組織障害と抗ドナー抗体の関連の検討2019

    • Author(s)
      入江理恵、福田晃也、阪本靖介、笠原群生
    • Organizer
      第23回日本肝臓学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] The outcome of children receiving macrosteatotic grafts from their parents2018

    • Author(s)
      Rie Irie
    • Organizer
      The 2018 Joint International Congress of ILTS, ELITA & LICAGE
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Living donor liver transplantation for hepatorenal fibrocystic disease in children2018

    • Author(s)
      Rie Irie
    • Organizer
      TTS2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 小児生体肝移植においてドナー肝の脂肪変性が予後に与える影響2018

    • Author(s)
      入江理恵
    • Organizer
      第107回日本病理学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 小児肝移植後早期の拒絶発症に関する因子の検討2018

    • Author(s)
      入江理恵
    • Organizer
      第22回日本肝臓学会大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 小児生体肝移植においてドナー肝の脂肪変性が予後に与える影響2018

    • Author(s)
      入江理恵
    • Organizer
      第54回移植学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Pathological signs of graft failure in pediatric patients after liver transplantation2017

    • Author(s)
      Rie Irie, Atsuko Nakazawa, Akinari Fukuda, Seisuke Sakamoto, Mureo Kasahara, Takako Yoshioka
    • Organizer
      The 2017 Joint International Congress of ILTS, ELITA & LICAGE
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 小児肝移植後グラフト不全の原因となる病理組織学的変化の検討2017

    • Author(s)
      入江理恵, 中澤温子, 佐々木健吾, 成本壮一, 福田晃也, 阪本靖介, 義岡孝子, 笠原群生
    • Organizer
      第53回日本移植学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 先天性肝線維症に対する生体肝移植におけるドナー肝の胆管形態と移植後予後に関する検討2017

    • Author(s)
      入江理恵, 成本壮一, 福田晃也, 阪本靖介, 笠原群生
    • Organizer
      第21回日本肝臓学会大会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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