Circulating Elastin Fragments Are Not Affected by Hepatic, Renal and Hemodynamic Changes, But Reflect Survival in Cirrhosis with TIPS

Research output: Contribution to journalJournal articleResearchpeer-review

  • M. J. Nielsen
  • J Lehmann
  • D J Leeming
  • R Schierwagen
  • S. Klein
  • C Jansen
  • C P Strassburg
  • Bendtsen, Flemming
  • S Møller
  • T Sauerbruch
  • Morten A Karsdal
  • A Krag
  • J Trebicka

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.

Original languageEnglish
JournalDigestive Diseases and Sciences
Volume60
Issue number11
Pages (from-to)3456-64
Number of pages9
ISSN0163-2116
DOIs
Publication statusPublished - Nov 2015

    Research areas

  • Adult, Aged, Aged, 80 and over, Biomarkers, Elastin, Enzyme-Linked Immunosorbent Assay, Female, Hemodynamics, Hepatorenal Syndrome, Humans, Hypertension, Portal, Kaplan-Meier Estimate, Kidney Function Tests, Liver Circulation, Liver Cirrhosis, Liver Function Tests, Male, Middle Aged, Multivariate Analysis, Peptide Fragments, Portal Vein, Portasystemic Shunt, Transjugular Intrahepatic, Predictive Value of Tests, Proportional Hazards Models, Risk Factors, Severity of Illness Index, Time Factors, Treatment Outcome

ID: 162453069