Biomarkers of extracellular matrix formation are associated with acute-on-chronic liver failure
Background & Aims: Acute-on-chronic liver failure (ACLF) is characterised by organ failure(s), high short-term mortality, and, pathophysiologically, deranged inflammatory responses. The extracellular matrix (ECM) is critically involved in regulating the inflammatory response. This study aime...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Elsevier
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/60899aef3e0647849024975785540415 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:60899aef3e0647849024975785540415 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:60899aef3e06478490249757855404152021-11-20T05:11:35ZBiomarkers of extracellular matrix formation are associated with acute-on-chronic liver failure2589-555910.1016/j.jhepr.2021.100355https://doaj.org/article/60899aef3e06478490249757855404152021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589555921001312https://doaj.org/toc/2589-5559Background & Aims: Acute-on-chronic liver failure (ACLF) is characterised by organ failure(s), high short-term mortality, and, pathophysiologically, deranged inflammatory responses. The extracellular matrix (ECM) is critically involved in regulating the inflammatory response. This study aimed to determine alterations in biomarkers of ECM turnover in ACLF and their association with inflammation, organ failures, and mortality. Methods: We studied 283 patients with cirrhosis admitted for acute decompensation (AD) with or without ACLF, 64 patients with stable cirrhosis, and 30 healthy controls. A validation cohort (25 ACLF, 9 healthy controls) was included. Plasma PRO-C3, PRO-C4, PRO-C5, PRO-C6, and PRO-C8 (i.e. collagen type III–VI and VIII formation) and C4M and C6M (i.e. collagen type IV and VI degradation) were measured. Immunohistochemistry of PRO-C6 was performed on liver biopsies (AD [n = 7], ACLF [n = 5]). A competing-risk regression analysis was performed to explore the prognostic value of biomarkers of ECM turnover with 28- and 90-day mortality. Results: PRO-C3 and PRO-C6 were increased in ACLF compared to AD (p = 0.089 and p <0.001, respectively), whereas collagen degradation markers C4M and C6M were similar. Both PRO-C3 and PRO-C6 were strongly associated with liver function and inflammatory markers. Only PRO-C6 was associated with extrahepatic organ failures and 28- and 90-day mortality (hazard ratio [HR; on log-scale] 6.168, 95% CI 2.366–16.080, p <0.001, and 3.495, 95% CI 1.509–8.093, p = 0.003, respectively). These findings were consistent in the validation cohort. High PRO-C6 expression was observed in liver biopsies of patients with ACLF. Conclusions: This study shows, for the first time, evidence of severe net interstitial collagen deposition in ACLF and makes the novel observation of the association between PRO-C6 and (extrahepatic) organ failures and mortality. Further studies are needed to define the pathogenic significance of these observations. Lay summary: This study describes a disrupted turnover of collagen type III and VI in Acute-on-chronic liver failure (ACLF). Plasma biomarkers of these collagens (PRO-C3 and PRO-C6) are associated with the severity of liver dysfunction and inflammation. PRO-C6, also known as the hormone endotrophin, has also been found to be associated with multi-organ failure and prognosis in acute decompensation and ACLF.Annarein J.C. KerbertSaurabh GuptaEman AlabsawyIwona DoblerIda LønsmannAndrew HallSigne Holm NielsenMette J. NielsenHenning GronbaekÀlex AmorosDave YeungJane MacnaughtanRajeshwar P. MookerjeeStewart MacdonaldFausto AndreolaRichard MoreauVicente ArroyoPaolo AngeliDiana J. LeemingWilliam TreemMorten A. KarsdalRajiv JalanElsevierarticleLiver cirrhosisMulti-organ failureCollagenPrognosisDiseases of the digestive system. GastroenterologyRC799-869ENJHEP Reports, Vol 3, Iss 6, Pp 100355- (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Liver cirrhosis Multi-organ failure Collagen Prognosis Diseases of the digestive system. Gastroenterology RC799-869 |
| spellingShingle |
Liver cirrhosis Multi-organ failure Collagen Prognosis Diseases of the digestive system. Gastroenterology RC799-869 Annarein J.C. Kerbert Saurabh Gupta Eman Alabsawy Iwona Dobler Ida Lønsmann Andrew Hall Signe Holm Nielsen Mette J. Nielsen Henning Gronbaek Àlex Amoros Dave Yeung Jane Macnaughtan Rajeshwar P. Mookerjee Stewart Macdonald Fausto Andreola Richard Moreau Vicente Arroyo Paolo Angeli Diana J. Leeming William Treem Morten A. Karsdal Rajiv Jalan Biomarkers of extracellular matrix formation are associated with acute-on-chronic liver failure |
| description |
Background & Aims: Acute-on-chronic liver failure (ACLF) is characterised by organ failure(s), high short-term mortality, and, pathophysiologically, deranged inflammatory responses. The extracellular matrix (ECM) is critically involved in regulating the inflammatory response. This study aimed to determine alterations in biomarkers of ECM turnover in ACLF and their association with inflammation, organ failures, and mortality. Methods: We studied 283 patients with cirrhosis admitted for acute decompensation (AD) with or without ACLF, 64 patients with stable cirrhosis, and 30 healthy controls. A validation cohort (25 ACLF, 9 healthy controls) was included. Plasma PRO-C3, PRO-C4, PRO-C5, PRO-C6, and PRO-C8 (i.e. collagen type III–VI and VIII formation) and C4M and C6M (i.e. collagen type IV and VI degradation) were measured. Immunohistochemistry of PRO-C6 was performed on liver biopsies (AD [n = 7], ACLF [n = 5]). A competing-risk regression analysis was performed to explore the prognostic value of biomarkers of ECM turnover with 28- and 90-day mortality. Results: PRO-C3 and PRO-C6 were increased in ACLF compared to AD (p = 0.089 and p <0.001, respectively), whereas collagen degradation markers C4M and C6M were similar. Both PRO-C3 and PRO-C6 were strongly associated with liver function and inflammatory markers. Only PRO-C6 was associated with extrahepatic organ failures and 28- and 90-day mortality (hazard ratio [HR; on log-scale] 6.168, 95% CI 2.366–16.080, p <0.001, and 3.495, 95% CI 1.509–8.093, p = 0.003, respectively). These findings were consistent in the validation cohort. High PRO-C6 expression was observed in liver biopsies of patients with ACLF. Conclusions: This study shows, for the first time, evidence of severe net interstitial collagen deposition in ACLF and makes the novel observation of the association between PRO-C6 and (extrahepatic) organ failures and mortality. Further studies are needed to define the pathogenic significance of these observations. Lay summary: This study describes a disrupted turnover of collagen type III and VI in Acute-on-chronic liver failure (ACLF). Plasma biomarkers of these collagens (PRO-C3 and PRO-C6) are associated with the severity of liver dysfunction and inflammation. PRO-C6, also known as the hormone endotrophin, has also been found to be associated with multi-organ failure and prognosis in acute decompensation and ACLF. |
| format |
article |
| author |
Annarein J.C. Kerbert Saurabh Gupta Eman Alabsawy Iwona Dobler Ida Lønsmann Andrew Hall Signe Holm Nielsen Mette J. Nielsen Henning Gronbaek Àlex Amoros Dave Yeung Jane Macnaughtan Rajeshwar P. Mookerjee Stewart Macdonald Fausto Andreola Richard Moreau Vicente Arroyo Paolo Angeli Diana J. Leeming William Treem Morten A. Karsdal Rajiv Jalan |
| author_facet |
Annarein J.C. Kerbert Saurabh Gupta Eman Alabsawy Iwona Dobler Ida Lønsmann Andrew Hall Signe Holm Nielsen Mette J. Nielsen Henning Gronbaek Àlex Amoros Dave Yeung Jane Macnaughtan Rajeshwar P. Mookerjee Stewart Macdonald Fausto Andreola Richard Moreau Vicente Arroyo Paolo Angeli Diana J. Leeming William Treem Morten A. Karsdal Rajiv Jalan |
| author_sort |
Annarein J.C. Kerbert |
| title |
Biomarkers of extracellular matrix formation are associated with acute-on-chronic liver failure |
| title_short |
Biomarkers of extracellular matrix formation are associated with acute-on-chronic liver failure |
| title_full |
Biomarkers of extracellular matrix formation are associated with acute-on-chronic liver failure |
| title_fullStr |
Biomarkers of extracellular matrix formation are associated with acute-on-chronic liver failure |
| title_full_unstemmed |
Biomarkers of extracellular matrix formation are associated with acute-on-chronic liver failure |
| title_sort |
biomarkers of extracellular matrix formation are associated with acute-on-chronic liver failure |
| publisher |
Elsevier |
| publishDate |
2021 |
| url |
https://doaj.org/article/60899aef3e0647849024975785540415 |
| work_keys_str_mv |
AT annareinjckerbert biomarkersofextracellularmatrixformationareassociatedwithacuteonchronicliverfailure AT saurabhgupta biomarkersofextracellularmatrixformationareassociatedwithacuteonchronicliverfailure AT emanalabsawy biomarkersofextracellularmatrixformationareassociatedwithacuteonchronicliverfailure AT iwonadobler biomarkersofextracellularmatrixformationareassociatedwithacuteonchronicliverfailure AT idalønsmann biomarkersofextracellularmatrixformationareassociatedwithacuteonchronicliverfailure AT andrewhall biomarkersofextracellularmatrixformationareassociatedwithacuteonchronicliverfailure AT signeholmnielsen biomarkersofextracellularmatrixformationareassociatedwithacuteonchronicliverfailure AT mettejnielsen biomarkersofextracellularmatrixformationareassociatedwithacuteonchronicliverfailure AT henninggronbaek biomarkersofextracellularmatrixformationareassociatedwithacuteonchronicliverfailure AT alexamoros biomarkersofextracellularmatrixformationareassociatedwithacuteonchronicliverfailure AT daveyeung biomarkersofextracellularmatrixformationareassociatedwithacuteonchronicliverfailure AT janemacnaughtan biomarkersofextracellularmatrixformationareassociatedwithacuteonchronicliverfailure AT rajeshwarpmookerjee biomarkersofextracellularmatrixformationareassociatedwithacuteonchronicliverfailure AT stewartmacdonald biomarkersofextracellularmatrixformationareassociatedwithacuteonchronicliverfailure AT faustoandreola biomarkersofextracellularmatrixformationareassociatedwithacuteonchronicliverfailure AT richardmoreau biomarkersofextracellularmatrixformationareassociatedwithacuteonchronicliverfailure AT vicentearroyo biomarkersofextracellularmatrixformationareassociatedwithacuteonchronicliverfailure AT paoloangeli biomarkersofextracellularmatrixformationareassociatedwithacuteonchronicliverfailure AT dianajleeming biomarkersofextracellularmatrixformationareassociatedwithacuteonchronicliverfailure AT williamtreem biomarkersofextracellularmatrixformationareassociatedwithacuteonchronicliverfailure AT mortenakarsdal biomarkersofextracellularmatrixformationareassociatedwithacuteonchronicliverfailure AT rajivjalan biomarkersofextracellularmatrixformationareassociatedwithacuteonchronicliverfailure |
| _version_ |
1718419544225087488 |