title: Circulating Elastin Fragments Are Not Affected by Hepatic, Renal and Hemodynamic Changes, But Reflect Survival in Cirrhosis with TIPS.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Nordic Bioscience, Fibrosis Biology and Biomarkers, Herlev, Denmark.|Department of Gastroenterology, Odense Hospital, University of Southern Denmark, Odense, Denmark.
authors.forename: M J
authors.initials: MJ
authors.lastname: Nielsen
authors.affiliation: Department of Internal Medicine I, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Lehmann
authors.affiliation: Nordic Bioscience, Fibrosis Biology and Biomarkers, Herlev, Denmark.
authors.forename: D J
authors.initials: DJ
authors.lastname: Leeming
authors.affiliation: Department of Internal Medicine I, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Schierwagen
authors.affiliation: Department of Internal Medicine I, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Klein
authors.affiliation: Department of Internal Medicine I, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Jansen
authors.affiliation: Department of Internal Medicine I, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
authors.forename: C P
authors.initials: CP
authors.lastname: Strassburg
authors.affiliation: Gastrounit, Medical Division, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark.
authors.forename: F
authors.initials: F
authors.lastname: Bendtsen
authors.affiliation: 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.
authors.forename: S
authors.initials: S
authors.lastname: Møller
authors.affiliation: Department of Internal Medicine I, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Sauerbruch
authors.affiliation: Nordic Bioscience, Fibrosis Biology and Biomarkers, Herlev, Denmark.
authors.forename: M A
authors.initials: MA
authors.lastname: Karsdal
authors.affiliation: Department of Gastroenterology, Odense Hospital, University of Southern Denmark, Odense, Denmark.
authors.forename: A
authors.initials: A
authors.lastname: Krag
authors.affiliation: Department of Internal Medicine I, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany. jonel.trebicka@ukb.uni-bonn.de.
authors.forename: J
authors.initials: J
authors.lastname: Trebicka
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D004549:Elastin / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006439:Hemodynamics; D006530:Hepatorenal Syndrome / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology*; D006801:Humans; D006975:Hypertension, Portal / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology / Q000601:surgery*; D053208:Kaplan-Meier Estimate; D007677:Kidney Function Tests; D008102:Liver Circulation; D008103:Liver Cirrhosis / Q000097:blood* / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010446:Peptide Fragments / Q000097:blood*; D011169:Portal Vein / Q000503:physiopathology*; D019168:Portasystemic Shunt, Transjugular Intrahepatic / Q000009:adverse effects / Q000401:mortality; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D004549:Elastin
keywords: Cirrhosis; Elastin; Portal hypertension; Transjugular intrahepatic portosystemic shunt