Background: Liver graft steatosis, especially macrosteatosis induces severe graft injury post-liver transplantation (LT) by activating cell-mediated immunity and inflammation. This study aimed to determine differential circulating chemokines in LT recipients.

Samples/Methods: This study included 27 LT that received grafts with different degree of steatosis. Study groups included LT patients receiving livers without (<5%; NS, n=13) or with macrosteatosis (10-30%; MS, n=14). EDTA-anticoagulated blood samples (n=76) were drawn from NS LT recipients at pre- (P1), post-reperfusion (P2), and day 1 (POD1) (NS-P1, n=12; NS-P2, n=13; NS-POD1, n=13) and MS LT recipients (MS-P1, n=12; MS-P2, n=12; MS-POD1, n=14). Plasma was obtained by blood centrifugation. Chemokines were tested by a pre-designed human chemokine panel bead-array (40 cytokines/chemokines) by Luminex. Unpaired t-test was fit (p<0.05). IPA tool was used for biological interpretation. Pearson's correlation was fit for chemokines and transaminases (p<0.05).

Results: Patient's demographics and clinical characteristics were similar between groups. Transaminases were significantly higher in LT patients receiving a steatotic graft at POD1 (AST, p=0.007; ALT, p=0.002) as well as the significant increase of circulating concentrations of 30 chemokines at post-reperfusion. Concentrations of CXCL2, CCL2, MIF, CCL3, IL6, and IL10 were significantly higher in MS group at P2. Longitudinal analyses of concentrations determined significant sustained increment of IFNg, IL1b, IL2, TNFa, CXCL13, CXCL5, CCL26, CX3CL1, CCL1, CXCL8, CCL7, CXCL16, and IL16 until POD1 in MS LT cases. However, concentrations of CCL21, MCP4, and CXCL12 were significantly lower (while CCL20 increased) in MS group at POD1. Biological interpretation suggested significant increment of granulocytes influx and communication of innate and adaptive immune response cells in MS LT. Furthermore, a significant positive correlation was identified between levels of AST and concentrations of CCL21 (r=0.550; p=0.041) at POD1,as well as CXCL8 (r=0.668; p=0.018), IL16 (r=0.742; p=0.006), and MCP1 (r=0.782; p=0.003) in MS LT patients at post-reperfusion time.

Conclusion: Post-reperfusion injury severity in steatotic livers correlates with a significant increase of inflammatory chemokines, accompanied by an overlapping of innate and adaptive immune responses.

CITATION INFORMATION: Gehrau R, Mas V, Sharma A, Bontha V, Maluf D. Liver Graft Steatosis Associates with an Increase of Circulating Immune Response Chemokines. Am J Transplant. 2016;16 (suppl 3).

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