AASLD Abstracts (pp. 484A–585A)
Authors: Masato Marubashi, Hiroaki Sakon, Atsushi Nagano, Keizo Miyamoto, Shoji Dono, Koji Nakamori, Morito Umeshitu, Shinji Shimoda, Takashi Kamihira, Eric Gershwin, Akihiko Okumura, Tetsuya Ishikawa, Ken Sato, Minoru Ayada, Tadashi Maeno, Naoki Hotta, Tsuneaki Tagaya, Yoshitaka Fukuzawa, Shinichi Kakumu, Maria Longhi, Yun Ma, Giorgina Mieli-Vergani, Diego Vergani, David Sass, Syuichi Koarada, Hong Yue, Noreen Wu, Michael Fertig, John Todd, Paul Lyons, Judith Fenyk- Melody, Linda Wicker, Laurence Peterson, William Xidgway, Stephan Schrarnm, Uniuersity Kanzler, Germany Of Mninz, Hans Weidenbach, Peter Galle, Ansgar Lohse, Regan Ebbeson, Richard Sckreiber
Journal: Hepatology (2003)

BuckgroundlAims: The role of portal-hemodynamics on liver injury and regeneration after partial hepatectomy is not fully understood, although several growth factors such as hepatocyte growth factor (HGF), tumor necrosis factor (TNF) -a, and Interleukin (IL) -6 are proved to be related.The aim of our study was to characterize the effects of portal-hemodynamics with HGF, TNF-a, and IL-6 on liver regeneration using a newly established rat model.Methods: We established a novel rat model of portohepatic shunt and 70% hepatectomy (PHS model), in which the portal pressure remained stable during and for 24 hours after 70% hepatectomy, confirmed by electric manometer directly placed into portal vein.To assess the effect of portal hemodynamics on liver injury and regeneration in the first 24 hours after hepatectomy, we measured (1) survival, (2) transaminase, (3) remnant liver weight, (4) characteristics of the remnant livers (histology with H&E stain, transferase-mediated dUTP nick end-labeling (TUNEL), BrdU incorporation), ( 5) IL-6, TNF-a, and Cyclin B mRNA in the remnant livers, at 6,12,18,24 hours after the procedures.Further, we measured the concentration of HGF in blood and the remnant liver, and studied activation of HGF in liver tissue using westernblot analysis.We compared data of PHS rats (n=6) with those with simple 70% hepatectomy (Control) (n=6).Results: PHS rats could not survive more than 48 hours in spite of no surgical or hemodynamical complications (mean survival, 22 hours), whereas all control rats could.Biochemical and histological changes were similar between two groups.Liver weight increased in control, whereas it did not in PHS group.(Pc0.05)There was no enlargement of hepatocytes in PHS, although DNA synthesis measured by proliferative cell nuclear antigen index, 5-bromo-2'-deoxyuridine incorporation, and the expression of Cyclin B mRNA developed similarly in both groups.Apoptotic hepatocytes detected using TUNEL method increased markedly in PHS on 24 hours, whereas minimal apoptosis was noted throughout the course in control.Hepatocyte growth factor (HGF) increased similarly, except HGF was not activated in PHS.Conclusions: Our results suggest that portal hyper-dynamic state early after 70Y0 hepatectomy was necessary for rats to survive.Hepatocyte hypertrophy seemed dependent on portal hemodynamics, but DNA synthesis in hepatocytes was not.Activation of HGF may have a key role in hepatocyte proliferation under portal hyper-dynamic state.