Liver manipulation causes hepatocyte injury and precedes systemic inflammation in patients undergoing liver resection.
BACKGROUND
Liver failure following liver surgery is caused by an insufficient functioning remnant cell mass. This can be due to insufficient liver volume and can be aggravated by additional cell death during or after surgery. The aim of this study was to elucidate the causes of hepatocellular injury in patients undergoing liver resection.


METHODS
Markers of hepatocyte injury (AST, GSTalpha, and L-FABP) and inflammation (IL-6) were measured in plasma of patients undergoing liver resection with and without intermittent inflow occlusion. To study the separate involvement of the intestines and the liver in systemic L-FABP release, arteriovenous concentration differences for L-FABP were measured.


RESULTS
During liver manipulation, liver injury markers increased significantly. Arterial plasma levels and transhepatic and transintestinal concentration gradients of L-FABP indicated that this increase was exclusively due to hepatic and not due to intestinal release. Intermittent hepatic inflow occlusion, anesthesia, and liver transection did not further enhance arterial L-FABP and GSTalpha levels. Hepatocyte injury was followed by an inflammatory response.


CONCLUSIONS
This study shows that liver manipulation is a leading cause of hepatocyte injury during liver surgery. A potential causal relation between liver manipulation and systemic inflammation remains to be established; but since the inflammatory response is apparently initiated early during major abdominal surgery, interventions aimed at reducing postoperative inflammation and related complications should be started early during surgery or beforehand.
van de Poll
Marcel C G
MC
Department of Surgery, University Hospital Maastricht and Nutrition and Toxicology Research Institute (NUTRIM), Maastricht University, Maastricht, The Netherlands. mcg.vandepoll@ah.unimaas.nl
Derikx
Joep P M
JP
Buurman
Wim A
WA
Peters
Wilbert H M
WH
Roelofs
Hennie M J
HM
Wigmore
Stephen J
SJ
Dejong
Cornelis Hc
CH
D000328:Adult; D000368:Aged; D001219:Aspartate Aminotransferases / Q000097:blood; D050556:Fatty Acid-Binding Proteins / Q000097:blood; D005260:Female; D005982:Glutathione Transferase / Q000097:blood; D006498:Hepatectomy / Q000009:adverse effects*; D022781:Hepatocytes / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000209:etiology; D015850:Interleukin-6 / Q000097:blood; D007527:Isoenzymes / Q000097:blood; D008113:Liver Neoplasms / Q000601:surgery; D008297:Male; D008875:Middle Aged
C493319:FABP1 protein, human; D050556:Fatty Acid-Binding Proteins; D015850:Interleukin-6; D007527:Isoenzymes; D005982:Glutathione Transferase; C119995:glutathione S-transferase alpha; D001219:Aspartate Aminotransferases