Early post-operative measurement of cytokine plasma levels combined with pre-operative bilirubin levels identify high-risk patients after liver resection.

Identification of patients at risk of a complicated course after liver resection is crucial for adapting post-operative care. In the present study, we investigated the diagnostic value of the plasma levels of various cytokines obtained immediately after surgery. IL-6, IL-10, IL-8, monokine induced by interferon-γ (MIG), monocyte chemotactic protein-1 (MCP-1) and interferon-inducible protein-10 (IP-10) concentrations were measured in 26 patients after liver resection using a cytometric bead assay and were correlated with liver function, resectate weight, surgery duration, ischemia/reperfusion, hospitalization time and occurrence of complications. Patients with post-surgical complications showed distinctive patterns of IL-6 and IL-8 as early as minutes to hours after surgery. In addition, although pre-operative bilirubin in most patients remained within the normal range, a cut-off of 1 mg/dl separated the patients into groups with different profiles of IL-6, IL-8, and MCP-1 secretion and different likelihoods of experiencing post-operative complications (bilirubin levels ≥1.0 vs. <1.0 mg/dl; IL-6 (4 h): 701 vs. 265; IL-8 (6 h): 262 vs. 97 pg/ml; p<0.05 for both). Extended hospitalization, related to delayed recovery, was correlated with increased IL-8 and MCP-1 immediately after surgery. In conclusion, on the basis of these observations, we suggest that early measurement of post-operative levels of MCP-1, IL-6, and IL-8 can be used to identify individuals at risk of post-operative complications immediately after liver surgery.

Hypoxia and reoxygenation of primary human hepatocytes induce proteome changes of glucose metabolism, oxidative protection and peroxisomal function.

Protective hepatocellular responses to a hypoxic challenge are crucial to preserve liver function. The knowledge of affected metabolic functions could help assess and enhance hepatic ischemic tolerance. Here we studied adaptive mechanisms in human hepatocytes after hypoxia and reoxygenation using a proteomic approach. Proteins from primary hepatocytes were extracted after 6 h of hypoxia and 24 h of reoxygenation. The proteome was analyzed by 2D-electrophoresis. Densitometry and mass spectrometry (MALDI-TOF-MS) were used for protein identification. Two hundred and sixty-two spots were differentially analyzed and 33 spots displayed significant differences between hypoxic and normoxic cells. Seventeen proteins were identified by mass spectrometry. After hypoxia and reoxygenation the UTP-glucose-1-phosphate uridyltransferase, phosphoglycerate kinase1, fructose-1,6-bisphosphate aldolase, glyceraldehyde-3-phosphate dehydrogenase, fructose-1,6-bisphosphatase, thiosulfat-sulfurtransferase, thioredoxin peroxidase, peroxiredoxin III, and annexin A2 proteins were down-regulated. An increased expression was found for carbamoyl phosphate synthetase I, heat shock 70 kDa protein5, phosphoenolpyruvate carboxy-kinase, catalase isoform2, peroxiredoxin II, glutathione S-transferase, hydroxyacid oxidase1, and F1-ATP synthase, alpha subunit1. Hepatocellular adaptation to hypoxia and reoxygenation involve glucose metabolism, peroxisomal functions, and oxidative stress protection. The identified proteins can serve as possible diagnostic targets to monitor hepatic hypoxic tolerance e.g. in the context of liver surgery and transplantation.

Complement and neutrophil function changes after liver resection in humans.

BACKGROUND: Complement activation contributes to the regulation of liver regeneration after liver resection (LR) in mice. METHODS: We hypothesized that complement activation and changes in C5a-receptors (C5aR, C5L2) on polymorphonuclear cells (PMN) and monocytes are important in clinical LR. Anaphylatoxin and C5b9 plasma levels were measured (bead-array, ELISA) (25 patients) and receptor expression was assessed after LR (19 patients) (FACS). In vitro PMN C5a-dependent chemotactic response (7 patients) as well as L-selectin shedding and Mac-1 expression (3 patients) was determined. RESULTS: C3a increased after LR (31.1 +/- 4 before LR vs. 41.6 +/- 5 ng/ml, 30 min after LR, P < 0.01), as did C5b9 (12.7 +/- 1 before LR vs. 26.9 +/- 3 ng/ml, 60 min after LR, P < 0.001). C4a and C5a decreased after LR, by 25% 24 h after LR and 30% 2 h after LR, respectively (P < 0.01). C5L2 expression decreased at 4 h, rising at 24 h after LR (PMN: 6.3 +/- 1 before LR, 3.1 +/- 1, 4 h, 8.3 +/- 2, 24 h; P < 0.01). The receptor-related changes accompanied a diminished C5a-dependent chemotactic response by PMN (42.1 +/- 17 before LR vs. 2.1 +/- 3 4 h after LR; P < 0.01) and a reduction of activation upon C5a-R stimulation as measured by L-selectin shedding and Mac-1 expression on PMN. Changes in C5L2 expression on monocytes paralleled postoperative impairment of liver function. CONCLUSIONS: These results indicate that complement components are released after clinical LR and subsequently PMN display altered C5a-dependent functional responses.