Enhanced processing of von Willebrand factor reflects disease severity and discriminates severe portal hypertension in cirrhosis
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Enhanced processing of von Willebrand factor reflects disease severity and discriminates severe portal hypertension in cirrhosis. / Langholm, Lasse L.; Manon-Jensen, Tina; Karsdal, Morten A.; Bendtsen, Flemming; Leeming, Diana J.; Moller, Soren.
In: European journal of gastroenterology & hepatology, Vol. 31, No. 8, 2019, p. 1040-1048.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Enhanced processing of von Willebrand factor reflects disease severity and discriminates severe portal hypertension in cirrhosis
AU - Langholm, Lasse L.
AU - Manon-Jensen, Tina
AU - Karsdal, Morten A.
AU - Bendtsen, Flemming
AU - Leeming, Diana J.
AU - Moller, Soren
PY - 2019
Y1 - 2019
N2 - Objectives Portal hypertension in cirrhosis is associated with endothelial dysfunction, impaired wound healing, and decreased platelet count. Increased von Willebrand factor (VWF) formation has been suggested as a compensatory mechanism, but the role of VWF processing has not been directly assessed. The aim was to measure the processing of activated VWF (VWF-A) in addition to VWF release (VWF-N) to investigate the association of primary hemostasis with disease activity and portal hypertension in liver cirrhosis. Participants and methods Plasma samples from 105 participants undergoing liver vein catheterization and with liver cirrhosis of varying severity were included in the study together with 20 controls without liver disease. Competitive enzyme-linked immunosorbent assay format was used to estimate biomarkers of VWF turnover using neo-epitope-specific monoclonal antibodies. Results VWF-N levels and VWF-A levels were significantly elevated in cirrhotic patients compared with controls (P<0.0001), and both markers could discriminate mild from severe cirrhosis (VWF-N, P<0.0001; VWF-A, P<0.05). Both markers correlated well with increasing portal hypertension and could identify patients with clinically significant portal hypertension (VWF-N, area under the curve: 0.78; VWF-A, area under the curve: 0.67). Only VWF-A significantly separated compensated from decompensated patients (P<0.05). Conclusion The data indicate that both VWF release and processing of active VWF are increased in cirrhosis, reflecting ongoing wound healing initiation. VWF-N and VWF-A may specifically contain information to assess the presence and severity of PHT as an early indicator of cirrhosis, and for acute damage in decompensated cirrhosis. Whether the increased wound healing affects long-term outcome needs to be addressed in future studies. Copyright (C) 2019 Wolters Kluwer Health, Inc. All rights reserved.
AB - Objectives Portal hypertension in cirrhosis is associated with endothelial dysfunction, impaired wound healing, and decreased platelet count. Increased von Willebrand factor (VWF) formation has been suggested as a compensatory mechanism, but the role of VWF processing has not been directly assessed. The aim was to measure the processing of activated VWF (VWF-A) in addition to VWF release (VWF-N) to investigate the association of primary hemostasis with disease activity and portal hypertension in liver cirrhosis. Participants and methods Plasma samples from 105 participants undergoing liver vein catheterization and with liver cirrhosis of varying severity were included in the study together with 20 controls without liver disease. Competitive enzyme-linked immunosorbent assay format was used to estimate biomarkers of VWF turnover using neo-epitope-specific monoclonal antibodies. Results VWF-N levels and VWF-A levels were significantly elevated in cirrhotic patients compared with controls (P<0.0001), and both markers could discriminate mild from severe cirrhosis (VWF-N, P<0.0001; VWF-A, P<0.05). Both markers correlated well with increasing portal hypertension and could identify patients with clinically significant portal hypertension (VWF-N, area under the curve: 0.78; VWF-A, area under the curve: 0.67). Only VWF-A significantly separated compensated from decompensated patients (P<0.05). Conclusion The data indicate that both VWF release and processing of active VWF are increased in cirrhosis, reflecting ongoing wound healing initiation. VWF-N and VWF-A may specifically contain information to assess the presence and severity of PHT as an early indicator of cirrhosis, and for acute damage in decompensated cirrhosis. Whether the increased wound healing affects long-term outcome needs to be addressed in future studies. Copyright (C) 2019 Wolters Kluwer Health, Inc. All rights reserved.
KW - biomarkers
KW - cirrhosis
KW - inflammation
KW - portal hypertension
KW - wound healing
U2 - 10.1097/MEG.0000000000001380
DO - 10.1097/MEG.0000000000001380
M3 - Journal article
C2 - 30768435
VL - 31
SP - 1040
EP - 1048
JO - European Journal of Gastroenterology and Hepatology, Supplement
JF - European Journal of Gastroenterology and Hepatology, Supplement
SN - 0954-691X
IS - 8
ER -
ID: 225559949