Circulating extracellular vesicles predict outcome in patient undergoing transjugular intrahepatic portosystemic shunt (TIPS) placement

Scientific Reports, vol. 15, pp. 35015

Abstract

Portal hypertension is a primary cause of complications leading to significant morbidity and mortality in patients with cirrhosis. Transjugular intrahepatic portosystemic shunt (TIPS) insertion has improved survival in well-selected patients with refractory ascites and high-risk variceal bleeding. We investigated the prognostic role of circulating extracellular vesicles (EVs), which are known for their role in immunomodulation and intercellular communication, in patients undergoing TIPS. 141 patients undergoing TIPS placement were included in this retrospective analysis. Median EVs size (X50) and total serum concentration were determined by nanoparticle tracking analysis (NTA) prior to TIPS placement, and transplant-free 1-year survival was assessed using time-to event analysis and Cox regression. EVs size but not their concentration moderately correlated with MELD and Child-Pugh scores based on its correlation with bilirubin and international normalized ratio. In addition, a significant correlation of EVs concentration with platelet count and the immune activation marker soluble urokinase plasminogen activator receptor was observed. In univariate analysis, larger EVs size (> 243 nm) was associated with 1-year transplant-free survival after TIPS placement (p = 0.012; HR: 2.539), which remained significant after adjusting for MELD scores in multivariable Cox-regression analysis (p = 0.033; HR: 2.204). Larger EVs size indicates advanced stages of chronic liver disease and served as an independent predictor of transplantation-free survival after TIPS placement. Larger prospective studies are needed to confirm these findings and to identify patients at particularly high-risk following TIPS placement.

Authors 15

1. Sven Heiko Loosen corresponding

   Düsseldorf University Hospital · Heinrich Heine University Düsseldorf

   Affiliation as printed

   Center for Integrated Oncology Aachen-Bonn-Cologne-Düsseldorf (CIOABCD), Aachen, Germany. Sven.Loosen@med.uni-duesseldorf.de

   Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, 40225, Düsseldorf, Germany. Sven.Loosen@med.uni-duesseldorf.de

   Center for Integrated Oncology Aachen-Bonn-Cologne-Düsseldorf (CIOABCD), Aachen, Germany

   Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, 40225, Düsseldorf, Germany

2. Frederik J. Hansen

   Düsseldorf University Hospital · Heinrich Heine University Düsseldorf

   Affiliation as printed

   Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, 40225, Düsseldorf, Germany

3. Denis Schatilow

   Düsseldorf University Hospital · Heinrich Heine University Düsseldorf

   Affiliation as printed

   Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, 40225, Düsseldorf, Germany

4. Theresa Hildegard Wirtz Aachen Department of Medicine III

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Department of Medicine III, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany

5. Philipp Alexander Reuken

   Düsseldorf University Hospital · Heinrich Heine University Düsseldorf

   Affiliation as printed

   Department of Surgery, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, 40225, Düsseldorf, Germany

6. Johannes Georg Bode

   Düsseldorf University Hospital · Heinrich Heine University Düsseldorf

   Affiliation as printed

   Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, 40225, Düsseldorf, Germany

7. Anselm Kunstein

   Düsseldorf University Hospital · Heinrich Heine University Düsseldorf

   Affiliation as printed

   Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, 40225, Düsseldorf, Germany

8. Mihael Vucur

   Düsseldorf University Hospital · Heinrich Heine University Düsseldorf

   Affiliation as printed

   Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, 40225, Düsseldorf, Germany

9. Johanna Reißing Aachen Department of Medicine III

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Department of Medicine III, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany

10. Georg Flügen

    Düsseldorf University Hospital · Heinrich Heine University Düsseldorf

    Affiliation as printed

    Department of Surgery, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, 40225, Düsseldorf, Germany

11. M. Castoldi

    Düsseldorf University Hospital · Heinrich Heine University Düsseldorf

    Affiliation as printed

    Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, 40225, Düsseldorf, Germany

12. Andreas Stallmach

    Jena University Hospital

    Affiliation as printed

    Department of Internal Medicine IV, University Hospital Jena, Am Klinikum 1, 07747, Jena, Germany

13. Tom Luedde

    Düsseldorf University Hospital · Heinrich Heine University Düsseldorf

    Affiliation as printed

    Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, 40225, Düsseldorf, Germany

14. Tony Bruns Aachen Department of Medicine III

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    Department of Medicine III, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany

15. Christoph Roderburg corresponding

    Düsseldorf University Hospital · Heinrich Heine University Düsseldorf

    Affiliation as printed

    Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, 40225, Düsseldorf, Germany. Christoph.roderburg@med.uni-duesseldorf.de

    Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, 40225, Düsseldorf, Germany