M J Nielsen1,2, J Lehmann3, D J Leeming1, R Schierwagen3, S Klein3, C Jansen3, C P Strassburg3, F Bendtsen4, S Møller5, T Sauerbruch3, M A Karsdal1, A Krag2, J Trebicka6. 1. Nordic Bioscience, Fibrosis Biology and Biomarkers, Herlev, Denmark. 2. Department of Gastroenterology, Odense Hospital, University of Southern Denmark, Odense, Denmark. 3. Department of Internal Medicine I, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany. 4. Gastrounit, Medical Division, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark. 5. Department of Clinical Physiology and Nuclear Medicine, 239 Center for Functional and Diagnostic Imaging and Research, Faculty of Health Sciences Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark. 6. Department of Internal Medicine I, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany. jonel.trebicka@ukb.uni-bonn.de.
Abstract
BACKGROUND AND AIMS: Progressive fibrosis increases hepatic resistance and causes portal hypertension with complications. During progressive fibrosis remodeling and deposition of collagens and elastin occur. Elastin remodeling is crucially involved in fibrosis progression in animal models and human data. This study investigated the association of circulating elastin with the clinical outcome in cirrhotic patients with severe portal hypertension receiving transjugular intrahepatic porto-systemic shunt (TIPS). METHODS: We analyzed portal and hepatic venous samples of 110 cirrhotic patients obtained at TIPS insertion and 2 weeks later. The circulating levels of elastin fragments (ELM) were determined using specific monoclonal ELISA. The relationship of ELM with clinical short-time follow-up and long-term outcome was investigated. RESULTS: Circulating levels of ELM showed a gradient across the liver before TIPS with higher levels in the hepatic vein. Interestingly, the circulating ELM levels remained unchanged after TIPS. The circulating levels of ELM in portal and hepatic veins correlated with platelet counts and inversely with serum sodium. Hepatic venous levels of ELM were higher in CHILD C compared to CHILD A and B and were associated with the presence of ascites. Patients with high levels of ELM in the hepatic veins before TIPS showed poorer survival. In multivariate analysis ELM levels in the hepatic veins and MELD were independent predictors of mortality in these patients. CONCLUSION: This study demonstrated that circulating levels of ELM are not associated with hemodynamic changes, but might reflect fibrosis remodeling and predict survival in patients with severe portal hypertension receiving TIPS independently of MELD.
BACKGROUND AND AIMS: Progressive fibrosis increases hepatic resistance and causes portal hypertension with complications. During progressive fibrosis remodeling and deposition of collagens and elastin occur. Elastin remodeling is crucially involved in fibrosis progression in animal models and human data. This study investigated the association of circulating elastin with the clinical outcome in cirrhoticpatients with severe portal hypertension receiving transjugular intrahepatic porto-systemic shunt (TIPS). METHODS: We analyzed portal and hepatic venous samples of 110 cirrhoticpatients obtained at TIPS insertion and 2 weeks later. The circulating levels of elastin fragments (ELM) were determined using specific monoclonal ELISA. The relationship of ELM with clinical short-time follow-up and long-term outcome was investigated. RESULTS: Circulating levels of ELM showed a gradient across the liver before TIPS with higher levels in the hepatic vein. Interestingly, the circulating ELM levels remained unchanged after TIPS. The circulating levels of ELM in portal and hepatic veins correlated with platelet counts and inversely with serum sodium. Hepatic venous levels of ELM were higher in CHILD C compared to CHILD A and B and were associated with the presence of ascites. Patients with high levels of ELM in the hepatic veins before TIPS showed poorer survival. In multivariate analysis ELM levels in the hepatic veins and MELD were independent predictors of mortality in these patients. CONCLUSION: This study demonstrated that circulating levels of ELM are not associated with hemodynamic changes, but might reflect fibrosis remodeling and predict survival in patients with severe portal hypertension receiving TIPS independently of MELD.
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Authors: Helene Skjøt-Arkil; Rikke E Clausen; Quoc Hai Trieu Nguyen; Yaguo Wang; Qinlong Zheng; Fernando J Martinez; Cory M Hogaboam; Meilan Han; Lloyd B Klickstein; Martin R Larsen; Arkadiusz Nawrocki; Diana J Leeming; Morten A Karsdal Journal: BMC Pulm Med Date: 2012-07-20 Impact factor: 3.317
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Authors: Christian Jansen; Hannah Eischeid; Jan Goertzen; Robert Schierwagen; Evrim Anadol; Christian P Strassburg; Tilman Sauerbruch; Margarete Odenthal; Jonel Trebicka Journal: PLoS One Date: 2014-07-28 Impact factor: 3.240
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Authors: 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 Journal: JHEP Rep Date: 2020-12-17
Authors: Johannes Chang; Avend Bamarni; Nina Böhling; Xin Zhou; Leah-Marie Klein; Jonathan Meinke; Georg Daniel Duerr; Philipp Lingohr; Sven Wehner; Maximilian J Brol; Jürgen K Rockstroh; Jörg C Kalff; Steffen Manekeller; Carsten Meyer; Ulrich Spengler; Christian Jansen; Vicente Arroyo; Christian P Strassburg; Jonel Trebicka; Michael Praktiknjo Journal: Hepatol Commun Date: 2021-03-26