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. 2007 Oct;31(10):2033-8.
doi: 10.1007/s00268-007-9182-4.

Liver manipulation causes hepatocyte injury and precedes systemic inflammation in patients undergoing liver resection

Marcel C G van de Poll  1 , Joep P M Derikx, Wim A Buurman, Wilbert H M Peters, Hennie M J Roelofs, Stephen J Wigmore, Cornelis Hc Dejong
Affiliations

Liver manipulation causes hepatocyte injury and precedes systemic inflammation in patients undergoing liver resection

Marcel C G van de Poll et al. World J Surg. 2007 Oct.

Abstract

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.

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Figures

Fig. 1
Fig. 1
Mean (SEM) arterial L-FABP (a), GSTα (b), and AST (c) levels in patients undergoing liver surgery with intermittent Pringle maneuver (n = 9). Plasma levels of all liver injury markers increased early during surgery, during liver manipulation (p < 0.05). Intermittent Pringle maneuver (2 × 15 min ischemia and 5 min reperfusion) did not cause significant changes in arterial L-FABP or GSTα levels, whereas AST gradually kept increasing. L-FABP and GSTα levels decreased immediately postoperatively (p = 0.03 and p = 0.004, respectively). *p < 0.05, ns = not significant; I = ischemia, R = reperfusion
Fig. 2
Fig. 2
Mean (SEM) plasma L-FABP levels in four patients undergoing lower abdominal surgery without manipulation of the liver. No changes in L-FABP concentration were observed
Fig. 3
Fig. 3
Mean (SEM) arteriovenous concentration gradients of L-FABP across the intestines (portal vein minus artery), the liver (hepatic vein minus portal vein), and the kidney in patients undergoing liver resection (n = 10). L-FABP was specifically released from the liver (p < 0.0001 vs. zero) and removed from circulation by the kidneys (p < 0.0001 vs. zero)
Fig. 4
Fig. 4
Fractional renal clearance of L-FABP in patients undergoing liver resection (n = 10). From the fractional renal extraction of FABPs (approximately 30%) and renal blood flow (22% of total blood volume per minute) [12], a plasma half-life of FABPs of 11 min can be calculated. [A] = arterial concentration, [RV] = renal venous concentration
Fig. 5
Fig. 5
Mean (SEM) arterial IL-6 concentration before, during, and after liver resection with intermittent Pringle maneuver (n = 9). * = first timepoint where p < 0.05 vs. baseline; I = ischemia, R = reperfusion
See this image and copyright information in PMC

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