Introduction In a recent study we coincidentally showed that mobilisation of the liver was a major cause of liver surgery-induced damage. The magnitude of and mechanisms by which this damage occurs are unknown.
Aim (A) To determine the relative contribution of mobilisation during liver surgery to liver damage and (B) To examine whether there is an association between mobilisation-induced liver damage and liver inflammation.
Method Consecutive patients undergoing liver surgery requiring full mobilisation of the right hemi-liver were included. Plasma samples and liver biopsies were obtained immediately after induction, prior to and directly after liver mobilisation, and after liver transection. Liver Fatty Acid Binding Protein (L-FABP) and alanine aminotranferase (ALAT) were analysed as markers of hepatocyte injury. Specimens were stained by immunohistochemistry for myeloperoxidase (MPO), human neutrophil peptide (HNP), and caspase-3-mediated cleavage generated neo-epitope of CK18 (M30). Gene expression of interleukin (IL) 1β, 6 and 8, and intercellular adhesion molecule (ICAM) were analysed by q-RT-PCR.
Results Nineteen patients were included (11M/8F, median age 64 years [30–79]) who underwent major liver surgery. L-FABP levels increased significantly during liver mobilisation (from 91.7 ng/ml [11.4–2212.5 ng/ml] to 1014.4 ng/ml [141.4–8986.1 ng/ml], p<0.001) and did not increase significantly thereafter (1315.2 ng/ml [67.0–20 099.2 ng/ml], p=0.75). L-FABP levels after ≥60 min mobilisation time were significantly higher when compared to ≥60 min mobilisation (1679.7 ng/ml vs 645.9 ng/ml, p=0.04). ALAT levels increased significantly from 26 IU/l [13–147] before to 130 IU/l [74–813] after liver mobilisation and to 275 IU/l [13–1352] after transection (all p<0.05). Liver mobilisation increased the numbers of positive cells in staining for MPO (p=0.0007), HNP (p=0.03), and M30 (p=0.01), whereas transaction led to no further increase thereafter. Liver mobilisation increased the gene expression of IL1b (p=0.01), IL-6 (p=0.08), IL-8 (p=0.02) and ICAM (p=0.007). Expression increases ranged from 2.8-fold in ICAM to 130-fold in IL-6. After transection, mRNA levels increased even further in IL-6 (p=0.004), IL-8 (p=0.0004) and ICAM (p=0.02), but not IL1b (p=0.32).
Conclusion Mobilisation of the liver during surgery induces profound hepatocellular damage and inflammation, which is associated with activation and/or infiltration of immune cells. Given the short half-life of L-FABP (14 min), hepatocyte damage predominantly occurred during mobilisation of the liver and not during transaction. These data produce insight into the mechanisms of mobilisation-induced liver damage, and provide indications for designing interventions aiming at prevention of surgery-induced liver damage in the future.
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