2003 Fiscal Year Annual Research Report

成人生体肝移植の展開と確立―遺伝子解析に基づく免疫抑制療法の開発―

Research Project

Project/Area Number	13307038
Research Institution	KYOTO UNIVERSITY
Principal Investigator	田中紘一京都大学, 医学研究科, 教授 (20115877)
Co-Investigator(Kenkyū-buntansha)	江川裕人京都大学, 医学研究科, 助教授 (40293865) 木内哲也名古屋大学, 医学研究科, 教授 (40303820) 上本伸二三重大学, 医学部, 教授 (40252449) 笠原群生京都大学, 医学研究科, 助手 (30324651) 貝原聡京都府立医科大学, 医学部, 助教授 (70324647)
Keywords	肝移植 / 成人肝移植ドナー / 免疫抑制療法 / メモリーT細胞 / エフェクターT細胞 / チトクロームP450 / P糖蛋白
Research Abstract	1998年より成人生体肝移植を本格的に導入しその展開と確立に努めてきた。この研究期間で、3DCTに基づくコンピューター画像解析による肝脈管構築の正確な分析をして、これに基づく安全性の高い肝グラフトの選択と手術手技を確立した。その結果成人生体肝移植は当施設において急速に進展して適応症例の拡大、症例数の増加、成績向上をもたらし、社会に大きく貢献した。しかしながらその成績は術前から種々の臓器障害が認められる高リスク群では術後合併症による早期死亡例も少なくない。この改善の為の最大のポイントは個々の患者に対する最適な免疫抑制療法と免疫不全に伴う感染症対策である。そこで免疫抑制剤タクロリムスの代謝について小腸粘膜の薬剤代謝に関与するCyp3a4,5とP糖蛋白分析を行い、個々の患者の免疫抑制薬物代謝の違いを明らかにした。また、術前術後に経時的に末梢血リンパ球・T細胞のうちナイーブT細胞/メモリーT細胞とエフェクターT細胞/メモリーT細胞の分析を中心にCD45 isoform expression profilingを行った。この結果に基づいて術前患者を5群のクラスに階層化することができ、それに応じて免疫抑制剤の至適投与量と投与方法を決定するテーラーメイド免疫抑制療法を確立する可能性を明らかにした。この研究により、成人生体肝移植は今後さらに安全に展開できる方向性を得た。

Research Products

(29 results)

All Other

All Publications (29 results)

[Publications] Akira Katsurada: "Circulating Antibody To Hepatitis B Core Antigen Does Not Always Reflect The Latent Hepatitis B Virus Infection In the Liver Tissue"Hepatology Reserch. 25. 105-114 (2003)
[Publications] M.Kido: "Significant Role Of Middle Hepatic Vein In Remnant Liver Regeneration Of Right- Lobe Living Donors"Transprantation. 75・9. 1598-1600 (2003)
[Publications] Kasahara M: "Living-Relate Liver Transplantation For Alagille Syndrome"Transplantation. 75・12. 2147-2150 (2003)
[Publications] Ito T: "Changes In Portal Venous Pressure In The Early Phase After Living Donoe Liver Transplantation : Pathogenesis and Clinical Implications"Transplantation. 75・8. 1313-1317 (2003)
[Publications] Kasahara M: "Monosegmental Living Donor Liver Transplantation For Infantile Hepatic Hemangioendothelioma"J Pediatr Surg. 38・7. 1108-1111 (2003)
[Publications] Hideaki Okajima: "Long- Term Effect Of Liver Transplantation On Bone Mineral Density In Children With End- Stage Liver Disease : A2-Year Prospective Study"Liver Transplantation. 9・4. 360-364 (2003)
[Publications] Koichi Tanaka: "Progress And Future In Living Donor Liver Transplantation"The Keio Journal Of Medicine. 52・2. 73-79 (2003)
[Publications] Ronald W.Busuttil: "Liver Transplantation"Liver Transplantation. 9・7. 651-663 (2003)
[Publications] Takashi Ito: "Surgery-Related Morbidity In Living Donors Of Rightlobe Liver Graft : Lessons From The First 200 Cases"Transplantation. 76・1. 158-163 (2003)
[Publications] Hidekazu Yamamoto: "Background And Clinical Impact Of Tissue Congestion In Right-Lobe Livingdonor Liver Grafts : A Magnetic Resonance Imaging Study"Transplantation. 1・76. 944-950 (2003)
[Publications] Mikiko Ueda: "A Case Of Inflammatory Pseudotumor Of The Liver Hilum Succcessfully Treated With Aggressive Hepatectomy"Journal Of Pediatric Surgery. 38・11. 9-11 (2003)
[Publications] Hironori Haga: "Periportal Edema And Necrosis As Diagnostic Histologic Features Of Early Humoral Rejection In A B O- Incompatible Liver Transplantation"Liver Transplantation. 9・12. 1-12 (2003)
[Publications] Hiroshi Hisatsune: "Endoscopic Management Of Billary Strictures Aafter Duct-To-Duct Biliary Reconstruction In Right-Love Living-Donor Liver Transplantation"Transplantation. 76・5. 810-815 (2003)
[Publications] Tetsuya Kiuchi: "Small-For-Saize Graft In Living Donor Liver Transplantation : How Far Should We Go?"Liver Transplantation. 9・9. 29-35 (2003)
[Publications] Yasuhiro Ogura: "Outcomes For Pediatric Liver Retransplantation From Living Donors"Transplantation. 76・6. 943-948 (2003)
[Publications] Koji Umeshita: "Operative Morbidity Of Living Liver Donors In Japan"The Lancet. 362. 687-690 (2003)
[Publications] Takashi Ito: "Surgery-Related morbidity In Living Donors Of Right-Robe Liver Graft : Lessons From The First 200 Cases"Transplantation. 76・1. 158-163 (2003)
[Publications] Mikiko Ueda: "A Case Of Inflammaatory Pseudotumor Of The Liver Hilum Successfully Tread With Aggressive Hepatectomy"Journal Of Pediatric Surgery. 38・11. 9-11 (2003)
[Publications] Satohiro Masuda: "Enhanced Expression Of Enterocyte P-Glycoprotein Depresses Cyclosporine Bioavailability In A Recipient Of Living Donor Liver Transplantation"Liver Transplantation. 9・11. 1108-1113 (2003)
[Publications] Koji Umeshita: "Operative Morbidity Of Living Liverdonors In Japan"The Lancet. (2003)
[Publications] 伊藤孝司: "肝静脈再建のテクニック"外科. 65. 52-57 (2003)
[Publications] 松本慎一: "膵島移植の最近の進歩"医学のあゆみ. 204. 506-507 (2003)
[Publications] 八木真太郎: "臓器移植と輸液・栄養管理"外科治療. 88. 290-294 (2003)
[Publications] 深津祥央: "タクロリムス免疫抑制導入プロトコールの創意による治療成績・副作用発言頻度の比較検討"日本TDM学会. 20. 95-96 (2003)
[Publications] 上田幹子: "肝芽腫と肝移植"小児外科. 35. 591-595 (2003)
[Publications] 小倉靖弘: "肝移植における適応の限界"Medical science Digest. 29. 10-13 (2003)
[Publications] 田中紘一: "Frontiers in Gastroenterology"メディカルレビュー社. 8. 46-50 (2003)
[Publications] 小倉靖弘: "ABO血液型不適合生体肝移植におけるアスペルギルス感染症"日本医学館. 117-122 (2003)
[Publications] 小柴貴明: "生体肝移植と免疫寛容"BIO Clinica. 18. 76-81 (2003)

2003 Fiscal Year Annual Research Report

成人生体肝移植の展開と確立―遺伝子解析に基づく免疫抑制療法の開発―

Principal Investigator

田中 紘一 京都大学, 医学研究科, 教授 (20115877)

Research Products

[Publications] Akira Katsurada: "Circulating Antibody To Hepatitis B Core Antigen Does Not Always Reflect The Latent Hepatitis B Virus Infection In the Liver Tissue"Hepatology Reserch. 25. 105-114 (2003)

[Publications] M.Kido: "Significant Role Of Middle Hepatic Vein In Remnant Liver Regeneration Of Right- Lobe Living Donors"Transprantation. 75・9. 1598-1600 (2003)

[Publications] Kasahara M: "Living-Relate Liver Transplantation For Alagille Syndrome"Transplantation. 75・12. 2147-2150 (2003)

[Publications] Ito T: "Changes In Portal Venous Pressure In The Early Phase After Living Donoe Liver Transplantation : Pathogenesis and Clinical Implications"Transplantation. 75・8. 1313-1317 (2003)

[Publications] Kasahara M: "Monosegmental Living Donor Liver Transplantation For Infantile Hepatic Hemangioendothelioma"J Pediatr Surg. 38・7. 1108-1111 (2003)

[Publications] Hideaki Okajima: "Long- Term Effect Of Liver Transplantation On Bone Mineral Density In Children With End- Stage Liver Disease : A2-Year Prospective Study"Liver Transplantation. 9・4. 360-364 (2003)

[Publications] Koichi Tanaka: "Progress And Future In Living Donor Liver Transplantation"The Keio Journal Of Medicine. 52・2. 73-79 (2003)

[Publications] Ronald W.Busuttil: "Liver Transplantation"Liver Transplantation. 9・7. 651-663 (2003)

[Publications] Takashi Ito: "Surgery-Related Morbidity In Living Donors Of Rightlobe Liver Graft : Lessons From The First 200 Cases"Transplantation. 76・1. 158-163 (2003)

[Publications] Hidekazu Yamamoto: "Background And Clinical Impact Of Tissue Congestion In Right-Lobe Livingdonor Liver Grafts : A Magnetic Resonance Imaging Study"Transplantation. 1・76. 944-950 (2003)

[Publications] Mikiko Ueda: "A Case Of Inflammatory Pseudotumor Of The Liver Hilum Succcessfully Treated With Aggressive Hepatectomy"Journal Of Pediatric Surgery. 38・11. 9-11 (2003)

[Publications] Hironori Haga: "Periportal Edema And Necrosis As Diagnostic Histologic Features Of Early Humoral Rejection In A B O- Incompatible Liver Transplantation"Liver Transplantation. 9・12. 1-12 (2003)

[Publications] Hiroshi Hisatsune: "Endoscopic Management Of Billary Strictures Aafter Duct-To-Duct Biliary Reconstruction In Right-Love Living-Donor Liver Transplantation"Transplantation. 76・5. 810-815 (2003)

[Publications] Tetsuya Kiuchi: "Small-For-Saize Graft In Living Donor Liver Transplantation : How Far Should We Go?"Liver Transplantation. 9・9. 29-35 (2003)

[Publications] Yasuhiro Ogura: "Outcomes For Pediatric Liver Retransplantation From Living Donors"Transplantation. 76・6. 943-948 (2003)

[Publications] Koji Umeshita: "Operative Morbidity Of Living Liver Donors In Japan"The Lancet. 362. 687-690 (2003)

[Publications] Takashi Ito: "Surgery-Related morbidity In Living Donors Of Right-Robe Liver Graft : Lessons From The First 200 Cases"Transplantation. 76・1. 158-163 (2003)

[Publications] Mikiko Ueda: "A Case Of Inflammaatory Pseudotumor Of The Liver Hilum Successfully Tread With Aggressive Hepatectomy"Journal Of Pediatric Surgery. 38・11. 9-11 (2003)

[Publications] Satohiro Masuda: "Enhanced Expression Of Enterocyte P-Glycoprotein Depresses Cyclosporine Bioavailability In A Recipient Of Living Donor Liver Transplantation"Liver Transplantation. 9・11. 1108-1113 (2003)

[Publications] Koji Umeshita: "Operative Morbidity Of Living Liverdonors In Japan"The Lancet. (2003)

[Publications] 伊藤孝司: "肝静脈再建のテクニック"外科. 65. 52-57 (2003)

[Publications] 松本慎一: "膵島移植の最近の進歩"医学のあゆみ. 204. 506-507 (2003)

[Publications] 八木真太郎: "臓器移植と輸液・栄養管理"外科治療. 88. 290-294 (2003)

[Publications] 深津祥央: "タクロリムス免疫抑制導入プロトコールの創意による治療成績・副作用発言頻度の比較検討"日本TDM学会. 20. 95-96 (2003)

[Publications] 上田幹子: "肝芽腫と肝移植"小児外科. 35. 591-595 (2003)

[Publications] 小倉靖弘: "肝移植における適応の限界"Medical science Digest. 29. 10-13 (2003)

[Publications] 田中紘一: "Frontiers in Gastroenterology"メディカルレビュー社. 8. 46-50 (2003)

[Publications] 小倉靖弘: "ABO血液型不適合生体肝移植におけるアスペルギルス感染症"日本医学館. 117-122 (2003)

[Publications] 小柴貴明: "生体肝移植と免疫寛容"BIO Clinica. 18. 76-81 (2003)

田中紘一京都大学, 医学研究科, 教授 (20115877)