Analysis of the role of hepatic remodeling and signal of hepatic regeneration after hepatic ischemia/reperfusion injury in obstructive jaundice

• Project/Area Number: 20591621
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Chiba University
• Principal Investigator: KATO Atsushi Chiba University, 大学院・医学研究院, 助教 (70344984)
• Co-Investigator(Kenkyū-buntansha): MIYAZAKI Masaru 千葉大学, 大学院・医学研究院, 教授 (70166156) ; SHIMIZU Hiroaki 千葉大学, 大学院・医学研究院, 講師 (80272318) ; YOSHIDOME Hiroyuki 千葉大学, 大学院・医学研究院, 講師 (10312935) ; FURUKAWA Katsunori 千葉大学, 医学部附属病院, 助教 (00400987)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 閉塞性黄疸 / 阻血再灌流 / 肝再生 / 転写因子 / 肝星細胞

Research Abstract

Cholestasis of the liver is known to be an important risk factor for surgical morbidity and mortality after major hepatectomy. However, the mechanism of liver injury in cholestatic liver is not fully understood. Our data suggests that hepatic stellate cell activation and increased endothelin-1 production play a crucial role in hepatic ischemia/reperfusion injury in cholestatic liver. To identify predictive factors for postoperative liver regeneration after major hepatectoy, clinical factors and liver volumetric changes determined by CT volumetry and CT attenuation values (CT-AVs) were compared in patients with and without postoperative hepatic failure. Postoperative lower CT-AV was the only independent risk factor of postoperative hepatic failure. Preoperative portal vein embolization (PVE) is an effective means of creating hypertrophy of future remaining liver, which leads to safety of extensive hepatectomy for hepatic malignancies. Plasma VEGF levels were increased markedly after PVE and were maximal after 7 days of PVE. Measurement of plasma VEGF levels after PVE may be a predictive factor of potential liver regeneration and may provide useful information to decide on the schedule of subsequent hepatectomy.

Research Products

• [Journal Article] Hepatocyte apoptosis is enhanced after ischemia/reperfusion in the steatotic liver. (2011)
  • Author(s): Suzuki T, Yoshidome H, Kimura F, Shimizu H, Ohtsuka M, Takeuchi D, Kato A, Furukawa K, Yoshitomi H, Iida A, Dochi T, Miyazaki M.
  • Journal Title: J Clin Biochem Nutr. 48 Pages: 142-148
  • NAID: 130004466631
  • Peer Reviewed
• [Journal Article] Hepatocyte apoptosis in enhanced after ischemia/reperfusion in the steatotic liver (2011)
  • Author(s): Suzuki T, Yoshidome H, ShimizuH, Kato A, et al
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: 48 Pages: 142-148
  • Peer Reviewed
• [Journal Article] Endothelin-1 aggravates hepatic ischemia/reperfusion injury during obstructive cholestasis in bile duct ligated mice. (2010)
  • Author(s): Nagai H, Kato A, Kimura F, Shimizu H, Yoshidome H, Ohtsuka M, Furukawa K, Nozawa S, Yoshitomi H, Mitsuhashi N, Takeuchi D, Suda K, Yoshioka I, Miyazaki M.
  • Journal Title: J Surg Res 162 Pages: 46-53
  • Peer Reviewed
• [Journal Article] Interleukin-18 exacerbates pulmonary injury after hepatic ischemia/reperfusion in mice. (2010)
  • Author(s): Takeuchi D, Yoshidome H, Kurosawa H, Kimura F, Shimizu H, Ohtsuka M, Kato A, Yoshitomi H, Furukawa K, Miyazaki M.
  • Journal Title: J Surg Res 158 Pages: 87-93
  • Peer Reviewed
• [Journal Article] Aggressive surgical resection for hilar cholangiocarcinoma of the left-side predominance : radicality and safety of left-sided hepatectomy. (2010)
  • Author(s): Shimizu H, Kimura F, Yoshidome H, Ohtsuka M, Kato A, Yoshitomi H, Furukawa K, Miyazaki M.
  • Journal Title: Ann Surg 251 Pages: 281-286
  • Peer Reviewed
• [Journal Article] One hundred seven consecutive surgical resections for hilar cholangiocarcinoma of Bismuth types II, III, IV between 2001 and 2008 (2010)
  • Author(s): Miyazaki M, Kimura F, Shimizu H, Yoshidome H, Otuka M, Kato A, Yoshitomi H, Furukawa K, Takeuchi D, Takayashiki T, Suda K, Takano S.
  • Journal Title: J Hepatobiliary Pancreat Sci 17 Pages: 470-475
  • NAID: 10027423555
  • Peer Reviewed
• [Journal Article] Endothelin-1 aggravates hepatic ischemia/reperfusion injury duringobstructive cholestasis in bile duct ligated mice. (2010)
  • Author(s): Hiroyuki Nagai, Atsushi Kato, Fumio Kimura, Hiroaki Shimizu, Hiroyuki Yoshidome, et al.
  • Journal Title: Journal of Surgical Research Volume: 162 Pages: 46-53
  • Peer Reviewed
• [Journal Article] Role of Kupffer cells in tolerance induction after portal venous administration of alloantigen. (2009)
  • Author(s): Shimizu H, Kataoka M, Kimura F, Yoshidome H, Ohtsuka M, Kato A, Miyazaki M.
  • Journal Title: Hepatogastroenterology 56 Pages: 783-787
  • Peer Reviewed
• [Journal Article] Effect of excessive acute-phase response on liver regeneration after partial hepatectomy in rats. (2009)
  • Author(s): Kusashio K, Shimizu H, Kimura F, Yoshidome H, Ohtsuka M, Kato A, Yoshitomi H, Furukawa K, Fukada T, Miyazaki M.
  • Journal Title: Hepatogastroenterology 56 Pages: 824-828
  • Peer Reviewed
• [Journal Article] Clinical significance of biliary vascular anatomy of the right liver for hilar cholangiocarcinoma applied to left hemihepatectomy. (2009)
  • Author(s): Shimizu H, Sawada S, Kimura F, Yoshidome H, Ohtsuka M, Kato A, Miyazaki M.
  • Journal Title: Ann Surg 249 Pages: 435-439
  • Peer Reviewed
• [Journal Article] Mechanism of neutrophil accumulation in sinusids after extrahepatic biliry obstruction. (2008)
  • Author(s): Wakabayashi Y, Shimizu H, Kimura F, Yoshidome H, Ohtsuka M, Kato A, Miyazaki M
  • Journal Title: Hapetogastroenterology 55 Pages: 1179-1183
  • Peer Reviewed
• [Journal Article] Endothelin-1 Aggravates Hepatic Ischemia/Reperfusion Injury During Obstructive Cholestasis in Bile Duct Ligated Mice.
  • Author(s): Hiroyuki Nagai, Atsushi Kato, Fumio Kimura, Hiroaki Shimizu, Hiroyuki Yoshidome, et al.
  • Journal Title: Journal of Surgical Research (In press)
  • Peer Reviewed
• [Journal Article] Endothelin-1 Aggravates Hepatic Ischemia/Reperfusion Injury During Obstructive Cholestasis in Bile Duct Ligated Mice.
  • Author(s): Hiroyuki Nagai, Atsushi Kato, Fumio Kimura, Hiroaki Shimizu, Hiroyuki Yoshidome, et al
  • Journal Title: Journal of Surgical Research (In press)
  • Peer Reviewed
• [Presentation] 胆道癌における拡大肝切除後の肝不全発症に肝再生は関係するか? (2010)
  • Author(s): 岡庭輝、加藤厚、木村文夫、清水宏明、吉留博之、大塚将之、吉富秀幸、古川勝規、宮崎勝, 他
  • Organizer: 第110回 日本外科学会定期学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2010-04-09
• [Presentation] 胆道癌における拡大肝切除後の肝不全発症に肝再生は関係するか? (2010)
  • Author(s): 岡庭輝、加藤厚, 他
  • Organizer: 第110回日本外科学会定期学術集会
  • Place of Presentation: 名古屋
• [Presentation] 肝胆道系悪性腫瘍に対する門脈塞栓術後の肝再生促進因子に関する検討 (2008)
  • Author(s): 加藤厚、木村文夫、清水宏明、吉留博之、大塚将之、吉富秀幸、古川勝規、宮崎勝, 他
  • Organizer: 第108回日本外科学会定期学術集会
  • Place of Presentation: 長崎
  • Year and Date: 2008-05-15