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Acute decompensation boosts hepatic collagen type III deposition and deteriorates experimental and human cirrhosis

Patients with end‐stage liver disease develop acute decompensation (AD) episodes, which become more frequent and might develop into acute‐on‐chronic liver failure (ACLF). However, it remains unknown how AD induces acceleration of liver disease. We hypothesized that remodeling of collagen type III pl...

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Autores principales: Praktiknjo, Michael, Lehmann, Jennifer, Nielsen, Mette J., Schierwagen, Robert, Uschner, Frank E., Meyer, Carsten, Thomas, Daniel, Strassburg, Christian P., Bendtsen, Flemming, Møller, Søren, Krag, Aleksander, Karsdal, Morten A., Leeming, Diana J., Trebicka, Jonel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5796334/
https://www.ncbi.nlm.nih.gov/pubmed/29404528
http://dx.doi.org/10.1002/hep4.1135
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author Praktiknjo, Michael
Lehmann, Jennifer
Nielsen, Mette J.
Schierwagen, Robert
Uschner, Frank E.
Meyer, Carsten
Thomas, Daniel
Strassburg, Christian P.
Bendtsen, Flemming
Møller, Søren
Krag, Aleksander
Karsdal, Morten A.
Leeming, Diana J.
Trebicka, Jonel
author_facet Praktiknjo, Michael
Lehmann, Jennifer
Nielsen, Mette J.
Schierwagen, Robert
Uschner, Frank E.
Meyer, Carsten
Thomas, Daniel
Strassburg, Christian P.
Bendtsen, Flemming
Møller, Søren
Krag, Aleksander
Karsdal, Morten A.
Leeming, Diana J.
Trebicka, Jonel
author_sort Praktiknjo, Michael
collection PubMed
description Patients with end‐stage liver disease develop acute decompensation (AD) episodes, which become more frequent and might develop into acute‐on‐chronic liver failure (ACLF). However, it remains unknown how AD induces acceleration of liver disease. We hypothesized that remodeling of collagen type III plays a role in the acceleration of liver cirrhosis after AD and analyzed its formation (Pro‐C3) and degradation (matrix metalloproteinase‐degraded type III collagen [C3M]) markers in animal models and human disease. Bile duct ligation induced different stages of liver fibrosis in rats. Fibrosis development (hydroxyprolin content, sirius red staining, α‐smooth muscle actin immunohistochemistry, messenger RNA of profibrotic cytokines), necroinflammation (aminotransferases levels), fibrolysis (matrix metalloproteinase 2 expression and activity, C1M, C4M), and Pro‐C3 and C3M were analyzed 2, 3, 4, 5, and 6 weeks after bile duct ligation (n = 5 each group). In 110 patients with decompensated liver cirrhosis who underwent a transjugular intrahepatic portosystemic shunt procedure for AD, clinical and laboratory parameters as well as Pro‐C3 and C3M were measured in blood samples from portal and hepatic veins and were collected just before the transjugular intrahepatic portosystemic shunt placement and 1‐3 weeks later. Animal studies showed increased markers of collagen type III deposition with fibrosis, necroinflammation, and decompensation of liver cirrhosis, defined as ascites development. Higher Pro‐C3 levels were associated with injury, disease severity scores (Model for End‐Stage Liver Disease, Child‐Pugh, chronic liver failure‐C AD), ACLF development, and mortality. C3M decreased with AD and the chronic liver failure‐C AD score. Collagen type III deposition ratio increased with the risk of ACLF development and mortality. Conclusion: We show for the first time that AD boosts collagen type III deposition in experimental and human cirrhosis, possibly contributing to the worsened outcome in patients with decompensated cirrhosis. (Hepatology Communications 2018;2:211–222)
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spelling pubmed-57963342018-02-05 Acute decompensation boosts hepatic collagen type III deposition and deteriorates experimental and human cirrhosis Praktiknjo, Michael Lehmann, Jennifer Nielsen, Mette J. Schierwagen, Robert Uschner, Frank E. Meyer, Carsten Thomas, Daniel Strassburg, Christian P. Bendtsen, Flemming Møller, Søren Krag, Aleksander Karsdal, Morten A. Leeming, Diana J. Trebicka, Jonel Hepatol Commun Original Articles Patients with end‐stage liver disease develop acute decompensation (AD) episodes, which become more frequent and might develop into acute‐on‐chronic liver failure (ACLF). However, it remains unknown how AD induces acceleration of liver disease. We hypothesized that remodeling of collagen type III plays a role in the acceleration of liver cirrhosis after AD and analyzed its formation (Pro‐C3) and degradation (matrix metalloproteinase‐degraded type III collagen [C3M]) markers in animal models and human disease. Bile duct ligation induced different stages of liver fibrosis in rats. Fibrosis development (hydroxyprolin content, sirius red staining, α‐smooth muscle actin immunohistochemistry, messenger RNA of profibrotic cytokines), necroinflammation (aminotransferases levels), fibrolysis (matrix metalloproteinase 2 expression and activity, C1M, C4M), and Pro‐C3 and C3M were analyzed 2, 3, 4, 5, and 6 weeks after bile duct ligation (n = 5 each group). In 110 patients with decompensated liver cirrhosis who underwent a transjugular intrahepatic portosystemic shunt procedure for AD, clinical and laboratory parameters as well as Pro‐C3 and C3M were measured in blood samples from portal and hepatic veins and were collected just before the transjugular intrahepatic portosystemic shunt placement and 1‐3 weeks later. Animal studies showed increased markers of collagen type III deposition with fibrosis, necroinflammation, and decompensation of liver cirrhosis, defined as ascites development. Higher Pro‐C3 levels were associated with injury, disease severity scores (Model for End‐Stage Liver Disease, Child‐Pugh, chronic liver failure‐C AD), ACLF development, and mortality. C3M decreased with AD and the chronic liver failure‐C AD score. Collagen type III deposition ratio increased with the risk of ACLF development and mortality. Conclusion: We show for the first time that AD boosts collagen type III deposition in experimental and human cirrhosis, possibly contributing to the worsened outcome in patients with decompensated cirrhosis. (Hepatology Communications 2018;2:211–222) John Wiley and Sons Inc. 2018-01-18 /pmc/articles/PMC5796334/ /pubmed/29404528 http://dx.doi.org/10.1002/hep4.1135 Text en © 2018 The Authors. Hepatology Communications published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Praktiknjo, Michael
Lehmann, Jennifer
Nielsen, Mette J.
Schierwagen, Robert
Uschner, Frank E.
Meyer, Carsten
Thomas, Daniel
Strassburg, Christian P.
Bendtsen, Flemming
Møller, Søren
Krag, Aleksander
Karsdal, Morten A.
Leeming, Diana J.
Trebicka, Jonel
Acute decompensation boosts hepatic collagen type III deposition and deteriorates experimental and human cirrhosis
title Acute decompensation boosts hepatic collagen type III deposition and deteriorates experimental and human cirrhosis
title_full Acute decompensation boosts hepatic collagen type III deposition and deteriorates experimental and human cirrhosis
title_fullStr Acute decompensation boosts hepatic collagen type III deposition and deteriorates experimental and human cirrhosis
title_full_unstemmed Acute decompensation boosts hepatic collagen type III deposition and deteriorates experimental and human cirrhosis
title_short Acute decompensation boosts hepatic collagen type III deposition and deteriorates experimental and human cirrhosis
title_sort acute decompensation boosts hepatic collagen type iii deposition and deteriorates experimental and human cirrhosis
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5796334/
https://www.ncbi.nlm.nih.gov/pubmed/29404528
http://dx.doi.org/10.1002/hep4.1135
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