Metabolomic biomarkers are associated with mortality in patients with cirrhosis caused by primary biliary cholangitis or primary sclerosing cholangitis

Aim: To assess the ability of signature metabolites alone, or in combination with the model for end-stage liver disease-Na (MELD-Na) score to predict mortality in patients with cirrhosis caused by primary biliary cholangitis or primary sclerosing cholangitis. Materials & methods: Plasma metaboli...

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Main Authors: Ayse L Mindikoglu, Cristian Coarfa, Antone R Opekun, Vijay H Shah, Juan P Arab, Konstantinos N Lazaridis, Nagireddy Putluri, Chandrashekar R Ambati, Matthew J Robertson, Sridevi Devaraj, Prasun K Jalal, Abbas Rana, John A Goss, Thomas C Dowling, Matthew R Weir, Stephen L Seliger, Jean-Pierre Raufman, David W Bernard, John M Vierling
Format: Article
Language:English
Published: Taylor & Francis Group 2020-02-01
Series:Future Science OA
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Online Access:https://www.future-science.com/doi/10.2144/fsoa-2019-0124
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author Ayse L Mindikoglu
Cristian Coarfa
Antone R Opekun
Vijay H Shah
Juan P Arab
Konstantinos N Lazaridis
Nagireddy Putluri
Chandrashekar R Ambati
Matthew J Robertson
Sridevi Devaraj
Prasun K Jalal
Abbas Rana
John A Goss
Thomas C Dowling
Matthew R Weir
Stephen L Seliger
Jean-Pierre Raufman
David W Bernard
John M Vierling
author_facet Ayse L Mindikoglu
Cristian Coarfa
Antone R Opekun
Vijay H Shah
Juan P Arab
Konstantinos N Lazaridis
Nagireddy Putluri
Chandrashekar R Ambati
Matthew J Robertson
Sridevi Devaraj
Prasun K Jalal
Abbas Rana
John A Goss
Thomas C Dowling
Matthew R Weir
Stephen L Seliger
Jean-Pierre Raufman
David W Bernard
John M Vierling
author_sort Ayse L Mindikoglu
collection DOAJ
description Aim: To assess the ability of signature metabolites alone, or in combination with the model for end-stage liver disease-Na (MELD-Na) score to predict mortality in patients with cirrhosis caused by primary biliary cholangitis or primary sclerosing cholangitis. Materials & methods: Plasma metabolites were detected using ultrahigh-performance liquid chromatography/tandem mass spectrometry in 39 patients with cirrhosis caused by primary biliary cholangitis or primary sclerosing cholangitis. Mortality was predicted using Cox proportional hazards regression and time-dependent receiver operating characteristic curve analyses. Results: The top five metabolites with significantly greater accuracy than the MELD-Na score (area under the receiver operating characteristic curve [AUROC] = 0.7591) to predict 1-year mortality were myo-inositol (AUROC = 0.9537), N-acetylputrescine (AUROC = 0.9018), trans-aconitate (AUROC = 0.8880), erythronate (AUROC = 0.8345) and N6-carbamoylthreonyladenosine (AUROC = 0.8055). Several combined MELD-Na-metabolite models increased the accuracy of predicted 1-year mortality substantially (AUROC increased from 0.7591 up to 0.9392). Conclusion: Plasma metabolites have the potential to enhance the accuracy of mortality predictions, minimize underestimates of mortality in patients with cirrhosis and low MELD-Na scores, and promote equitable allocation of donor livers.
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spelling doaj-art-67b9ede47d7a43a09cc32b36b4d67d972025-08-20T02:25:48ZengTaylor & Francis GroupFuture Science OA2056-56232020-02-016210.2144/fsoa-2019-0124Metabolomic biomarkers are associated with mortality in patients with cirrhosis caused by primary biliary cholangitis or primary sclerosing cholangitisAyse L Mindikoglu0Cristian Coarfa1Antone R Opekun2Vijay H Shah3Juan P Arab4Konstantinos N Lazaridis5Nagireddy Putluri6Chandrashekar R Ambati7Matthew J Robertson8Sridevi Devaraj9Prasun K Jalal10Abbas Rana11John A Goss12Thomas C Dowling13Matthew R Weir14Stephen L Seliger15Jean-Pierre Raufman16David W Bernard17John M Vierling181Margaret M & Albert B Alkek Department of Medicine, Section of Gastroenterology & Hepatology, Baylor College of Medicine, Houston, TX, USA3Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, TX, USA1Margaret M & Albert B Alkek Department of Medicine, Section of Gastroenterology & Hepatology, Baylor College of Medicine, Houston, TX, USA6Department of Medicine, Division of Gastroenterology & Hepatology, Mayo Clinic College of Medicine, Rochester, MN, USA7Departamento de Gastroenterologia, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile6Department of Medicine, Division of Gastroenterology & Hepatology, Mayo Clinic College of Medicine, Rochester, MN, USA3Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, TX, USA3Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, TX, USA3Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, TX, USA8Clinical Chemistry & Point of Care Technology, Texas Children's Hospital & Health Centers, Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, USA1Margaret M & Albert B Alkek Department of Medicine, Section of Gastroenterology & Hepatology, Baylor College of Medicine, Houston, TX, USA2Michael E DeBakey Department of Surgery, Division of Abdominal Transplantation, Baylor College of Medicine, Houston, TX, USA2Michael E DeBakey Department of Surgery, Division of Abdominal Transplantation, Baylor College of Medicine, Houston, TX, USA9Ferris State University, College of Pharmacy, Grand Rapids, MI, USA10Department of Medicine, Division of Nephrology, University of Maryland School of Medicine, Baltimore, MD, USA10Department of Medicine, Division of Nephrology, University of Maryland School of Medicine, Baltimore, MD, USA11Department of Medicine, Division of Gastroenterology & Hepatology, University of Maryland School of Medicine, Baltimore, MD, USA12Department of Pathology & Genomic Medicine, Houston Methodist Hospital, Houston, TX, USA1Margaret M & Albert B Alkek Department of Medicine, Section of Gastroenterology & Hepatology, Baylor College of Medicine, Houston, TX, USAAim: To assess the ability of signature metabolites alone, or in combination with the model for end-stage liver disease-Na (MELD-Na) score to predict mortality in patients with cirrhosis caused by primary biliary cholangitis or primary sclerosing cholangitis. Materials & methods: Plasma metabolites were detected using ultrahigh-performance liquid chromatography/tandem mass spectrometry in 39 patients with cirrhosis caused by primary biliary cholangitis or primary sclerosing cholangitis. Mortality was predicted using Cox proportional hazards regression and time-dependent receiver operating characteristic curve analyses. Results: The top five metabolites with significantly greater accuracy than the MELD-Na score (area under the receiver operating characteristic curve [AUROC] = 0.7591) to predict 1-year mortality were myo-inositol (AUROC = 0.9537), N-acetylputrescine (AUROC = 0.9018), trans-aconitate (AUROC = 0.8880), erythronate (AUROC = 0.8345) and N6-carbamoylthreonyladenosine (AUROC = 0.8055). Several combined MELD-Na-metabolite models increased the accuracy of predicted 1-year mortality substantially (AUROC increased from 0.7591 up to 0.9392). Conclusion: Plasma metabolites have the potential to enhance the accuracy of mortality predictions, minimize underestimates of mortality in patients with cirrhosis and low MELD-Na scores, and promote equitable allocation of donor livers.https://www.future-science.com/doi/10.2144/fsoa-2019-0124biomarkercirrhosisliver transplantationMELD-Na scoremetabolitemetabolomics
spellingShingle Ayse L Mindikoglu
Cristian Coarfa
Antone R Opekun
Vijay H Shah
Juan P Arab
Konstantinos N Lazaridis
Nagireddy Putluri
Chandrashekar R Ambati
Matthew J Robertson
Sridevi Devaraj
Prasun K Jalal
Abbas Rana
John A Goss
Thomas C Dowling
Matthew R Weir
Stephen L Seliger
Jean-Pierre Raufman
David W Bernard
John M Vierling
Metabolomic biomarkers are associated with mortality in patients with cirrhosis caused by primary biliary cholangitis or primary sclerosing cholangitis
Future Science OA
biomarker
cirrhosis
liver transplantation
MELD-Na score
metabolite
metabolomics
title Metabolomic biomarkers are associated with mortality in patients with cirrhosis caused by primary biliary cholangitis or primary sclerosing cholangitis
title_full Metabolomic biomarkers are associated with mortality in patients with cirrhosis caused by primary biliary cholangitis or primary sclerosing cholangitis
title_fullStr Metabolomic biomarkers are associated with mortality in patients with cirrhosis caused by primary biliary cholangitis or primary sclerosing cholangitis
title_full_unstemmed Metabolomic biomarkers are associated with mortality in patients with cirrhosis caused by primary biliary cholangitis or primary sclerosing cholangitis
title_short Metabolomic biomarkers are associated with mortality in patients with cirrhosis caused by primary biliary cholangitis or primary sclerosing cholangitis
title_sort metabolomic biomarkers are associated with mortality in patients with cirrhosis caused by primary biliary cholangitis or primary sclerosing cholangitis
topic biomarker
cirrhosis
liver transplantation
MELD-Na score
metabolite
metabolomics
url https://www.future-science.com/doi/10.2144/fsoa-2019-0124
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