title: Alpha-gluthathione S-transferase as an early marker of hepatic ischemia/reperfusion injury after liver resection.
abstract: Organ dysfunction following liver resection is one of the major postoperative complications of liver surgery. The Pringle maneuver is often applied during liver resection to minimize bleeding, which in turn complicates the postoperative course owing to liver ischemia and reperfusion. Routinely, hepatocellular damage is diagnosed by, for example, abnormal aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and the prothrombin time (PT). The cytosolic liver enzyme alpha-glutathione S-transferase (alpha-GST) has recently been shown to have good sensitivity for detecting hepatic injury after acetaminophen poisoning or liver transplantation, but its role in non-transplantation liver surgery has not been assessed. In this prospective randomized clinical study, the diagnostic role of plasma alpha-GST following warm ischemia and reperfusion is reported. A total of 75 patients who underwent liver resection were randomly assigned to three groups: (1) without Pringle (NPR); (2) with Pringle (PR); (3) with ischemic preconditioning by 10 minutes of ischemia and reperfusion each prior to the Pringle manuever (IPC). The major findings are as follows: (1) ALT, AST, and alpha-GST increased upon liver manipulation as early as prior to resection, with a rapid return of alpha-GST values to preoperative levels, whereas ALT and AST further increased on the first postoperative day. (2) In the PR group, alpha-GST, but not ALT and AST, was significantly elevated compared with that in the NPR group at 15 and 30 minutes and 2 hours after resection/reperfusion. In addition, only levels of alpha-GST significantly correlated with the Pringle duration. (3) The ischemia/reperfusion-induced early rise in alpha-GST was completely prevented by ischemic preconditioning. Moreover, only alpha-GST concentrations (> 490 microg L(-1)) determined early after resection (2 hours) predicted postoperative liver dysfunction (24 hours PT < 60%) with a positive predictive value of 74% and a negative predictive value of 76%. Thus alpha-GST seems to be a sensitive, predictive marker of ischemia/reperfusion-induced hepatocellular injury and postoperative liver dysfunction.
authors.affiliation: Department of Anesthesiology, Klinikum Grosshadern, Marchioninistrasse 15, Ludwig-Maximilians-University, Munich, D-81377, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Choukér
authors.forename: André
authors.initials: A
authors.lastname: Martignoni
authors.forename: Rolf J
authors.initials: RJ
authors.lastname: Schauer
authors.forename: Martin
authors.initials: M
authors.lastname: Dugas
authors.forename: Thomas
authors.initials: T
authors.lastname: Schachtner
authors.forename: Ines
authors.initials: I
authors.lastname: Kaufmann
authors.forename: Florian
authors.initials: F
authors.lastname: Setzer
authors.forename: Horst G
authors.initials: HG
authors.lastname: Rau
authors.forename: Florian
authors.initials: F
authors.lastname: Löhe
authors.forename: Karl W
authors.initials: KW
authors.lastname: Jauch
authors.forename: Klaus
authors.initials: K
authors.lastname: Peter
authors.forename: Manfred
authors.initials: M
authors.lastname: Thiel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000097:blood; D017544:Aortic Aneurysm, Abdominal / Q000601:surgery; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers; D005260:Female; D005982:Glutathione Transferase / Q000097:blood*; D006498:Hepatectomy / Q000009:adverse effects*; D006801:Humans; D019194:Ischemic Preconditioning; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011517:Prothrombin Time; D012372:ROC Curve; D015427:Reperfusion Injury / Q000175:diagnosis*
chemical_list: D015415:Biomarkers; D005982:Glutathione Transferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase