title: Elevated liver regeneration in response to pharmacological reduction of elevated portal venous pressure by terlipressin after partial hepatectomy.
abstract: BACKGROUND
  Liver regeneration is of crucial importance for patients undergoing living liver transplantations or extended liver resections and can be associated with elevated portal venous pressure, impaired hepatic regeneration, and postoperative morbidity. The aim of this study was to assess whether reduction of portal venous pressure by terlipressin improves postoperative liver regeneration in normal and steatotic livers after partial hepatectomy in a rodent model.
  
  
  METHODS
  Portal venous pressure was assessed after minor (30%), standard (60%), or extended (80%) partial hepatectomy (PH) in mice with and without liver steatosis. Liver regeneration was assessed by BrdU incorporation and Ki-67 immunostaining.
  
  
  RESULTS
  Portal venous pressure was significantly elevated post-PH in mice with normal and steatotic livers compared to sham-operated mice. Reduction of elevated portal pressure after 80% PH by terlipressin was associated with an increase of hepatocellular proliferation. In steatotic livers, animals treated with terlipressin had an increase in liver regeneration after 30% PH and increased survival after 60% PH. Mechanistically, terlipressin alleviated IL-6 mRNA expression following PH and down-regulated p21 and GADD45 mRNA suggesting a reduction of cell cycle inhibition and cellular stress.
  
  
  CONCLUSIONS
  Reduction of elevated portal pressure post-PH by the use of terlipressin improves liver regeneration after PH in lean and steatotic mouse livers.
authors.affiliation: 1 Division of Visceral Surgery and Medicine, Inselspital, University Hospital Bern, Bern, Switzerland. 2 Department of Clinical Research, Inselspital, University Hospital Bern, Bern, Switzerland. 3 Department of Pathology, Inselspital, University Hospital Bern, Bern, Switzerland. 4 Address correspondence to: Guido Beldi, M.D., Division of Visceral Surgery and Medicine, University Hospital Bern, CH-3010 Bern, Switzerland.
authors.forename: René
authors.initials: R
authors.lastname: Fahrner
authors.forename: Eleonora
authors.initials: E
authors.lastname: Patsenker
authors.forename: Andrea
authors.initials: A
authors.lastname: de Gottardi
authors.forename: Felix
authors.initials: F
authors.lastname: Stickel
authors.forename: Matteo
authors.initials: M
authors.lastname: Montani
authors.forename: Deborah
authors.initials: D
authors.lastname: Stroka
authors.forename: Daniel
authors.initials: D
authors.lastname: Candinas
authors.forename: Guido
authors.initials: G
authors.lastname: Beldi
mesh_terms: D000818:Animals; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D005234:Fatty Liver / Q000378:metabolism; D006498:Hepatectomy / Q000379:methods; D015850:Interleukin-6 / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000502:physiology* / Q000601:surgery; D008115:Liver Regeneration / Q000502:physiology*; D008236:Lypressin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000378:metabolism; D017082:Portal Pressure; D011169:Portal Vein / Q000473:pathology; D012038:Regeneration; D000077585:Terlipressin; D014662:Vasoconstrictor Agents / Q000627:therapeutic use; D000097642:GADD45 Proteins
chemical_list: D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D015850:Interleukin-6; D019394:Ki-67 Antigen; D008236:Lypressin; D009687:Nuclear Proteins; D000077585:Terlipressin; D014662:Vasoconstrictor Agents; C493957:Cdkn1a protein, mouse; C499072:Gadd45a protein, mouse; D000097642:GADD45 Proteins