title: Small liver remnants are more vulnerable to ischemia/reperfusion injury after extended hepatectomies: a case-control study.
abstract: BACKGROUND
  There is evidence that small-for-size liver grafts are more vulnerable to ischemia/reperfusion injury after liver transplantation. We hypothesized that ischemic injury is more pronounced in small liver remnants after major hepatectomies.
  
  
  METHODS
  Fifteen patients underwent extended hepatectomy with remnant liver mass less than 30% of standard liver weight (study group). These patients were matched with patients who underwent minor liver resection, with liver remnants equal to or more than 70% of standard liver weight (control group). Ischemia/reperfusion injury was assessed by tissue caspase-3 activity postoperatively as well as peak aspartate aminotransferase (AST) values and a-glutathione S-transferase (α-GST) levels adjusted for remnant liver weight. In addition, caspase-3 activity and adjusted serum markers of hepatocyte injury were correlated with the degree of postoperative portal hypertension.
  
  
  RESULTS
  Caspase-3 activity was higher in patients with small liver remnants (22.66±6.57 vs. 12.60±4.06 count per high-power field, p<0.001). Serum markers of hepatocyte injury, when adjusted per gram of liver remnant, were found to be higher in the study group than in the control group (AST: 1.26±0.25 vs. 0.54±0.11 IU g(-1), p<0.001; α-GST: 0.14±0.02 vs. 0.08±0.01 IU g(-1), p<0.001). Tissue caspase-3 expression in the small liver remnant group correlated with both AST and α-GST levels adjusted per gram of liver remnant (r2=0.51, p=0.005 and r2=0.71, p<0.001, respectively). Significant correlations between postoperative portal hypertension and the same markers as well as caspase-3 activity were also demonstrated.
  
  
  CONCLUSIONS
  Liver remnants less than 30% of standard liver weight are much more susceptible to ischemia/reperfusion injury than controls twice the size. Adjustment of serum markers of hepatocyte injury to the liver remnant weight depicts injury more accurately.
authors.affiliation: First Department of Anesthesiology, Aretaieion Hospital, University of Athens School of Medicine, Vassilissis Sofias 76, 11528, Athens, Greece. ktheodoraki@hotmail.com
authors.forename: Kassiani
authors.initials: K
authors.lastname: Theodoraki
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Arkadopoulos
authors.forename: Constantinos
authors.initials: C
authors.lastname: Nastos
authors.forename: Ioannis
authors.initials: I
authors.lastname: Vassiliou
authors.forename: Iosifina
authors.initials: I
authors.lastname: Karmaniolou
authors.forename: Vassilios
authors.initials: V
authors.lastname: Smyrniotis
mesh_terms: D000368:Aged; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D053148:Caspase 3 / Q000378:metabolism; D005260:Female; D005982:Glutathione Transferase / Q000097:blood; D006498:Hepatectomy; D006801:Humans; D006975:Hypertension, Portal / Q000201:enzymology / Q000209:etiology; D007527:Isoenzymes / Q000097:blood; D008099:Liver / Q000033:anatomy & histology* / Q000201:enzymology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D011183:Postoperative Complications / Q000201:enzymology; D015427:Reperfusion Injury / Q000175:diagnosis / Q000201:enzymology / Q000209:etiology*
chemical_list: D015415:Biomarkers; D007527:Isoenzymes; D005982:Glutathione Transferase; C119995:glutathione S-transferase alpha; D001219:Aspartate Aminotransferases; D053148:Caspase 3