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

TY - JOUR

T1 - Circulating Elastin Fragments Are Not Affected by Hepatic, Renal and Hemodynamic Changes, But Reflect Survival in Cirrhosis with TIPS

AU - Nielsen, M. J.

AU - Lehmann, J

AU - Leeming, D J

AU - Schierwagen, R

AU - Klein, S.

AU - Jansen, C

AU - Strassburg, C P

AU - Bendtsen, F

AU - Møller, S

AU - Sauerbruch, T

AU - Karsdal, Morten A

AU - Krag, A

AU - Trebicka, J

PY - 2015/11/1

Y1 - 2015/11/1

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Biomarkers

KW - Elastin

KW - Enzyme-Linked Immunosorbent Assay

KW - Female

KW - Hemodynamics

KW - Hepatorenal Syndrome

KW - Humans

KW - Hypertension, Portal

KW - Kaplan-Meier Estimate

KW - Kidney Function Tests

KW - Liver Circulation

KW - Liver Cirrhosis

KW - Liver Function Tests

KW - Male

KW - Middle Aged

KW - Multivariate Analysis

KW - Peptide Fragments

KW - Portal Vein

KW - Portasystemic Shunt, Transjugular Intrahepatic

KW - Predictive Value of Tests

KW - Proportional Hazards Models

KW - Risk Factors

KW - Severity of Illness Index

KW - Time Factors

KW - Treatment Outcome

U2 - 10.1007/s10620-015-3783-9

DO - 10.1007/s10620-015-3783-9

M3 - Journal article

C2 - 26138655

SN - 0163-2116

VL - 60

SP - 3456

EP - 3464

JO - Digestive Diseases and Sciences

JF - Digestive Diseases and Sciences

IS - 11

ER -