Graft‐derived macrophage migration inhibitory factor correlates with hepatocellular injury in patients undergoing liver transplantation

Baron-Stefaniak, Joanna; Schiefer, Judith; Miller, Edmund J.; Plöchl, Walter; Krenn, Claus G.; Berlakovich, Gabriela; Baron, David M.; Faybik, Peter

doi:10.1111/ctr.12982

Cited by 3 publications

(2 citation statements)

References 42 publications

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“…Immunosuppression was administered as previously described. 16 Demographic and etiological data, surgical reports, use of blood products, model of end-stage liver disease (MELD) score, and perioperative laboratory parameters (blood chemistry, coagulation, full blood count) were collected for each patient. Routinely measured laboratory parameters were extracted from the patient data management software (ICCA, Philips, The Netherlands).…”

Section: Patients and Perioperative Datamentioning

confidence: 99%

“…Furthermore, D-DT and MIF share the unique ability among all cytokines to antagonize the immunosuppressive effect of glucocorticoids. 3,7 Increased serum MIF concentrations have been demonstrated in various clinical settings, [8][9][10][11][12][13][14][15] including orthotopic liver transplantation (OLT), 16 and were associated with poor survival and kidney injury. In contrast, only few studies have been published on D-DT in humans.…”

Section: Introductionmentioning

confidence: 99%

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D-dopachrome tautomerase predicts outcome but not the development of acute kidney injury after orthotopic liver transplantation

Baron-Stefaniak

Schiefer

Lichtenegger

et al. 2019

HPB

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Background: Elevated concentrations of D-dopachrome tautomerase (D-DT) were associated with adverse outcome in various clinical settings. However, no study assessed D-DT concentrations in patients requiring orthotopic liver transplantation (OLT). The aim of this observational study was to measure serum D-DT concentrations in patients undergoing OLT and associate D-DT with survival and acute kidney injury (AKI). Methods: Forty-seven adults with end-stage liver disease undergoing OLT were included. Areas under the receiver operating curves (AUC) were calculated to assess predictive values of D-DT for outcome and AKI after OLT. Survival was analyzed by Kaplan-Meier curves. Results: Serum D-DT concentrations were greater in non-survivors than in survivors prior to OLT (86 [50-117] vs. 53 [31-71] ng/ml, P = 0.008), and on day 1 (357 [238-724] vs. 189 [135-309] ng/ml, P = 0.001) and day 2 (210 [142-471] vs. 159 [120-204] ng/ml, P = 0.004) following OLT. Serum D-DT concentrations predicted lethal outcome when measured preoperatively (AUC = 0.75, P = 0.017) and on postoperative day 1 (AUC = 0.75, P = 0.015). One-year survival of patients with preoperative D-DT concentrations >85 ng/ml was 50%, whereas that of patients with preoperative D-DT concentrations <85 ng/ml was 83% (Chi 2 = 5.83, P = 0.016). In contrast, D-DT was not associated with AKI after OLT. Conclusion: In patients undergoing OLT, serum D-DT might predict outcome after OLT.

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Section: Patients and Perioperative Datamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

D-dopachrome tautomerase predicts outcome but not the development of acute kidney injury after orthotopic liver transplantation

Baron-Stefaniak

Schiefer

Lichtenegger

et al. 2019

HPB

Self Cite

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The Role of Macrophage Migration Inhibitory Factor in Remote Ischemic Conditioning Induced Hepatoprotection in a Rodent Model of Liver Transplantation

Emontzpohl

Stoppe

Theißen

et al. 2019

Shock

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Background: Macrophage migration inhibitory factor (MIF) is an important stress-regulating mediator of acute ischemia/reperfusion (I/R) injury and ischemic conditioning. The present study aimed to investigate whether MIF is involved in the effects of remote ischemic conditioning (RIC) in a rat model of orthotopic liver transplantation (OLT). Methods: OLTs were performed in male Lewis rats (245 g–340 g). Recipients were allocated in a randomized fashion into three experimental groups: remote preconditioning-RIPC, remote post-conditioning-RIPOST, control. RIC was applied as 4×5-5 min I/R via clamping of the infrarenal aorta. Animals were followed for 1, 3, 24, 168 h post-reperfusion (n = 6 recipient/group/time point). Graft micro- and macrocirculation and hepatocellular damage were assessed. Messenger ribonucleic acid (mRNA) expression, serum, and tissue protein levels of MIF, as well as additional markers of I/R injury, were measured. Results: RIC resulted in a prominent downregulation of MIF mRNA, serum, and tissue protein. Compared with control, hepatocellular damage was significantly mitigated after RIPC or RIPOST (serum ALT; RIPC, RIPOST vs. Control, P = 0.008, P = 0.030, respectively). Graft circulation was better preserved in the RIC groups. Furthermore, there was a significant positive correlation between serum MIF and transaminase levels (r = 0.330; P = 0.02). RIC showed a significant effect on iNOS and STAT5 mRNA expressions. Supporting findings were obtained from the measurements of tissue CXCL12 mRNA expression and pAkt/Akt, pErk/Erk. Conclusion: In this sophisticated experimental model of OLT, RIC-induced hepatoprotective effects were associated with a downregulation of MIF at mRNA and protein levels, suggesting the role of MIF as a mediator in RIC-induced protection following OLT.

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Glycocalyx Damage Within Human Liver Grafts Correlates With Graft Injury and Postoperative Graft Function After Orthotopic Liver Transplantation

et al. 2020

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Background. Destruction of the endothelial glycocalyx has been observed within lung and kidney grafts during ischemic organ preservation. We aimed to quantify glycocalyx damage within human liver grafts after organ preservation and correlate the results with graft injury and postoperative graft function in patients undergoing orthotopic liver transplantation (OLT). Methods. Syndecan-1 (Sdc-1) was measured as indicator of glycocalyx degradation in effluents of 38 liver grafts and serum of patients undergoing OLT. Effluent Sdc-1 concentrations were correlated with hepatic injury markers from the effluent. Furthermore, we assessed the association of Sdc-1 with early allograft dysfunction (EAD), 1-year graft survival, and 1-year patient survival. Results. Effluent Sdc-1 concentrations correlated with effluent concentrations of hepatocellular injury markers, including alkaline phosphatase (R = 0.543, P = 0.003), aspartate aminotransferase (R = 0.420, P = 0.029), and lactate (R = 0.574, P = 0.002). Sdc-1 effluent concentrations were greater in patients who developed EAD compared with those without EAD (4720 [4374–5133] vs 3838 [3202–4240] ng/mL, P = 0.015). Furthermore, receiver operating characteristics analyses revealed that effluent Sdc-1 concentrations (AUC = 0.82, P = 0.017) and serum Sdc-1 concentrations (AUC = 0.84, P = 0.006) were associated with the development of EAD. These results were confirmed by regression analyses. No association was found between Sdc-1 and 1-year graft survival or 1-year patient survival. Conclusions. Our data suggest that the glycocalyx is damaged within human liver grafts during preservation and the extent of glycocalyx damage correlates with the severity of hepatocellular injury. Recipients of livers grafts with greater glycocalyx damage might be at higher risk for development of EAD after OLT.

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Graft‐derived macrophage migration inhibitory factor correlates with hepatocellular injury in patients undergoing liver transplantation

Abstract: Human liver grafts release MIF in proportion to hepatocellular injury. Greater MIF concentrations in effluent and recipient's serum are associated with EAD after liver transplantation.

Cited by 3 publications

References 42 publications

D-dopachrome tautomerase predicts outcome but not the development of acute kidney injury after orthotopic liver transplantation

D-dopachrome tautomerase predicts outcome but not the development of acute kidney injury after orthotopic liver transplantation

The Role of Macrophage Migration Inhibitory Factor in Remote Ischemic Conditioning Induced Hepatoprotection in a Rodent Model of Liver Transplantation

Glycocalyx Damage Within Human Liver Grafts Correlates With Graft Injury and Postoperative Graft Function After Orthotopic Liver Transplantation

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