Balance between macrophage migration inhibitory factor and sCD74 predicts outcome in patients with acute decompensation of cirrhosis
Background & Aims: Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine and an important regulator of innate immune responses. We hypothesised that serum concentrations of MIF are associated with disease severity and outcome in patients with decompensated cirrhosis and ac...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-04-01
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| Series: | JHEP Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589555920301555 |
| _version_ | 1818620258009743360 |
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| author | Theresa H. Wirtz Philipp A. Reuken Christian Jansen Petra Fischer Irina Bergmann Christina Backhaus Christoph Emontzpohl Johanna Reißing Elisa F. Brandt M. Teresa Koenen Kai M. Schneider Robert Schierwagen Maximilian J. Brol Johannes Chang Henning W. Zimmermann Nilay Köse-Vogel Thomas Eggermann Ingo Kurth Christian Stoppe Richard Bucala Jürgen Bernhagen Michael Praktiknjo Andreas Stallmach Christian Trautwein Jonel Trebicka Tony Bruns Marie-Luise Berres |
| author_facet | Theresa H. Wirtz Philipp A. Reuken Christian Jansen Petra Fischer Irina Bergmann Christina Backhaus Christoph Emontzpohl Johanna Reißing Elisa F. Brandt M. Teresa Koenen Kai M. Schneider Robert Schierwagen Maximilian J. Brol Johannes Chang Henning W. Zimmermann Nilay Köse-Vogel Thomas Eggermann Ingo Kurth Christian Stoppe Richard Bucala Jürgen Bernhagen Michael Praktiknjo Andreas Stallmach Christian Trautwein Jonel Trebicka Tony Bruns Marie-Luise Berres |
| author_sort | Theresa H. Wirtz |
| collection | DOAJ |
| description | Background & Aims: Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine and an important regulator of innate immune responses. We hypothesised that serum concentrations of MIF are associated with disease severity and outcome in patients with decompensated cirrhosis and acute-on-chronic liver failure (ACLF). Methods: Circulating concentrations of MIF and its soluble receptor CD74 (sCD74) were determined in sera from 292 patients with acute decompensation of cirrhosis defined as new onset or worsening of ascites requiring hospitalisation. Of those, 78 (27%) had ACLF. Short-term mortality was assessed 90 days after inclusion. Results: Although serum concentrations of MIF and sCD74 did not correlate with liver function parameters or ACLF, higher MIF (optimum cut-off >2.3 ng/ml) and lower concentrations of sCD74 (optimum cut-off <66.5 ng/ml) both indicated poorer 90-day transplant-free survival in univariate analyses (unadjusted hazard ratio [HR] 2.01 [1.26–3.22]; p = 0.004 for MIF; HR 0.59 [0.38–0.92]; p = 0.02 for sCD74) and after adjustment in multivariable models. Higher MIF concentrations correlated with surrogates of systemic inflammation (white blood cells, p = 0.005; C-reactive protein, p = 0.05) and were independent of genetic MIF promoter polymorphisms. Assessment of MIF plasma concentrations in portal venous blood and matched blood samples from the right atrium in a second cohort of patients undergoing transjugular intrahepatic portosystemic shunt insertion revealed a transhepatic MIF gradient with higher concentrations in the right atrial blood. Conclusions: Serum concentrations of MIF and its soluble receptor CD74 predict 90-day transplant-free survival in patients with acute decompensation of cirrhosis. This effect was independent of liver function and genetic predispositions, but rather reflected systemic inflammation. Therefore, MIF and sCD74 represent promising prognostic markers beyond classical scoring systems in patients at risk of ACLF. Lay summary: Inflammatory processes contribute to the increased risk of death in patients with cirrhosis and ascites. We show that patients with high serum levels of the inflammatory cytokine macrophage migration inhibitory factor (MIF) alongside low levels of its binding receptor sCD74 in blood indicate an increased mortality risk in patients with ascites. The cirrhotic liver is a relevant source of elevated circulating MIF levels. |
| first_indexed | 2024-12-16T17:50:31Z |
| format | Article |
| id | doaj.art-74e1d74705f34501b1c9829b64a7c90a |
| institution | Directory Open Access Journal |
| issn | 2589-5559 |
| language | English |
| last_indexed | 2024-12-16T17:50:31Z |
| publishDate | 2021-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JHEP Reports |
| spelling | doaj.art-74e1d74705f34501b1c9829b64a7c90a2022-12-21T22:22:20ZengElsevierJHEP Reports2589-55592021-04-0132100221Balance between macrophage migration inhibitory factor and sCD74 predicts outcome in patients with acute decompensation of cirrhosisTheresa H. Wirtz0Philipp A. Reuken1Christian Jansen2Petra Fischer3Irina Bergmann4Christina Backhaus5Christoph Emontzpohl6Johanna Reißing7Elisa F. Brandt8M. Teresa Koenen9Kai M. Schneider10Robert Schierwagen11Maximilian J. Brol12Johannes Chang13Henning W. Zimmermann14Nilay Köse-Vogel15Thomas Eggermann16Ingo Kurth17Christian Stoppe18Richard Bucala19Jürgen Bernhagen20Michael Praktiknjo21Andreas Stallmach22Christian Trautwein23Jonel Trebicka24Tony Bruns25Marie-Luise Berres26Department of Internal Medicine III, RWTH Aachen University Hospital, Aachen, Germany; Corresponding author. Address: Department of Internal Medicine III, RWTH Aachen University Hospital, Pauwelsstrasse 30, 52074 Aachen, Germany. Tel.: +49-241-80-80861; Fax: +49-241-80-82455.Department of Internal Medicine IV, Jena University Hospital, Friedrich Schiller University, Jena, GermanyDepartment of Internal Medicine I, University of Bonn, Bonn, GermanyDepartment of Internal Medicine III, RWTH Aachen University Hospital, Aachen, GermanyDepartment of Internal Medicine III, RWTH Aachen University Hospital, Aachen, GermanyInstitute of Human Genetics, Medical Faculty, RWTH Aachen, Aachen, GermanyDepartment of Anesthesiology, The University of Texas Health Science Center at Houston, Mc Govern Medical School, Houston, TX, USADepartment of Internal Medicine III, RWTH Aachen University Hospital, Aachen, GermanyDepartment of Internal Medicine III, RWTH Aachen University Hospital, Aachen, GermanyDepartment of Internal Medicine III, RWTH Aachen University Hospital, Aachen, GermanyDepartment of Internal Medicine III, RWTH Aachen University Hospital, Aachen, GermanyDepartment of Internal Medicine 1, University Hospital, Goethe University, Frankfurt, GermanyDepartment of Internal Medicine I, University of Bonn, Bonn, GermanyDepartment of Internal Medicine I, University of Bonn, Bonn, GermanyDepartment of Internal Medicine III, RWTH Aachen University Hospital, Aachen, GermanyDepartment of Internal Medicine IV, Jena University Hospital, Friedrich Schiller University, Jena, GermanyInstitute of Human Genetics, Medical Faculty, RWTH Aachen, Aachen, GermanyInstitute of Human Genetics, Medical Faculty, RWTH Aachen, Aachen, GermanyDepartment of Intensive Care Medicine, University Hospital Aachen, Aachen, GermanyDepartment of Internal Medicine, Yale University School of Medicine, New Haven, CT, USADepartment of Vascular Biology, Institute for Stroke and Dementia Research (ISD), Ludwig Maximilians-University (LMU), Munich, Germany; Munich Cluster for Systems Neurology (EXC 2145 SyNergy), Munich, GermanyDepartment of Internal Medicine I, University of Bonn, Bonn, GermanyDepartment of Internal Medicine IV, Jena University Hospital, Friedrich Schiller University, Jena, GermanyDepartment of Internal Medicine III, RWTH Aachen University Hospital, Aachen, GermanyDepartment of Internal Medicine 1, University Hospital, Goethe University, Frankfurt, GermanyDepartment of Internal Medicine III, RWTH Aachen University Hospital, Aachen, GermanyDepartment of Internal Medicine III, RWTH Aachen University Hospital, Aachen, GermanyBackground & Aims: Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine and an important regulator of innate immune responses. We hypothesised that serum concentrations of MIF are associated with disease severity and outcome in patients with decompensated cirrhosis and acute-on-chronic liver failure (ACLF). Methods: Circulating concentrations of MIF and its soluble receptor CD74 (sCD74) were determined in sera from 292 patients with acute decompensation of cirrhosis defined as new onset or worsening of ascites requiring hospitalisation. Of those, 78 (27%) had ACLF. Short-term mortality was assessed 90 days after inclusion. Results: Although serum concentrations of MIF and sCD74 did not correlate with liver function parameters or ACLF, higher MIF (optimum cut-off >2.3 ng/ml) and lower concentrations of sCD74 (optimum cut-off <66.5 ng/ml) both indicated poorer 90-day transplant-free survival in univariate analyses (unadjusted hazard ratio [HR] 2.01 [1.26–3.22]; p = 0.004 for MIF; HR 0.59 [0.38–0.92]; p = 0.02 for sCD74) and after adjustment in multivariable models. Higher MIF concentrations correlated with surrogates of systemic inflammation (white blood cells, p = 0.005; C-reactive protein, p = 0.05) and were independent of genetic MIF promoter polymorphisms. Assessment of MIF plasma concentrations in portal venous blood and matched blood samples from the right atrium in a second cohort of patients undergoing transjugular intrahepatic portosystemic shunt insertion revealed a transhepatic MIF gradient with higher concentrations in the right atrial blood. Conclusions: Serum concentrations of MIF and its soluble receptor CD74 predict 90-day transplant-free survival in patients with acute decompensation of cirrhosis. This effect was independent of liver function and genetic predispositions, but rather reflected systemic inflammation. Therefore, MIF and sCD74 represent promising prognostic markers beyond classical scoring systems in patients at risk of ACLF. Lay summary: Inflammatory processes contribute to the increased risk of death in patients with cirrhosis and ascites. We show that patients with high serum levels of the inflammatory cytokine macrophage migration inhibitory factor (MIF) alongside low levels of its binding receptor sCD74 in blood indicate an increased mortality risk in patients with ascites. The cirrhotic liver is a relevant source of elevated circulating MIF levels.http://www.sciencedirect.com/science/article/pii/S2589555920301555Acute-on-chronic liver failureInflammationLiver cirrhosisBiomarkerSurvival |
| spellingShingle | Theresa H. Wirtz Philipp A. Reuken Christian Jansen Petra Fischer Irina Bergmann Christina Backhaus Christoph Emontzpohl Johanna Reißing Elisa F. Brandt M. Teresa Koenen Kai M. Schneider Robert Schierwagen Maximilian J. Brol Johannes Chang Henning W. Zimmermann Nilay Köse-Vogel Thomas Eggermann Ingo Kurth Christian Stoppe Richard Bucala Jürgen Bernhagen Michael Praktiknjo Andreas Stallmach Christian Trautwein Jonel Trebicka Tony Bruns Marie-Luise Berres Balance between macrophage migration inhibitory factor and sCD74 predicts outcome in patients with acute decompensation of cirrhosis JHEP Reports Acute-on-chronic liver failure Inflammation Liver cirrhosis Biomarker Survival |
| title | Balance between macrophage migration inhibitory factor and sCD74 predicts outcome in patients with acute decompensation of cirrhosis |
| title_full | Balance between macrophage migration inhibitory factor and sCD74 predicts outcome in patients with acute decompensation of cirrhosis |
| title_fullStr | Balance between macrophage migration inhibitory factor and sCD74 predicts outcome in patients with acute decompensation of cirrhosis |
| title_full_unstemmed | Balance between macrophage migration inhibitory factor and sCD74 predicts outcome in patients with acute decompensation of cirrhosis |
| title_short | Balance between macrophage migration inhibitory factor and sCD74 predicts outcome in patients with acute decompensation of cirrhosis |
| title_sort | balance between macrophage migration inhibitory factor and scd74 predicts outcome in patients with acute decompensation of cirrhosis |
| topic | Acute-on-chronic liver failure Inflammation Liver cirrhosis Biomarker Survival |
| url | http://www.sciencedirect.com/science/article/pii/S2589555920301555 |
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