@article{f20e8c8fe43a422cadee67b2ae093ec9,
title = "Metabolomic biomarkers are associated with mortality in patients with cirrhosis caused by primary biliary cholangitis or primary sclerosing cholangitis",
abstract = "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.",
keywords = "MELD-Na score, biomarker, cirrhosis, liver transplantation, metabolite, metabolomics, mortality, myo-inositol, primary biliary cholangitis, primary sclerosing cholangitis",
author = "Mindikoglu, {Ayse L.} and Cristian Coarfa and Opekun, {Antone R.} and Shah, {Vijay H.} and Arab, {Juan P.} and Lazaridis, {Konstantinos N.} and Nagireddy Putluri and Ambati, {Chandrashekar R.} and Robertson, {Matthew J.} and Sridevi Devaraj and Jalal, {Prasun K.} and Abbas Rana and Goss, {John A.} and Dowling, {Thomas C.} and Weir, {Matthew R.} and Seliger, {Stephen L.} and Raufman, {Jean Pierre} and Bernard, {David W.} and Vierling, {John M.}",
note = "Funding Information: AL Mindikoglu was supported by 2017 Roderick D MacDonald Research Award/Baylor St Luke{\textquoteright}s Medical Center (award number 17RDM005). This project was also supported in part by NIH Public Health Service grant P30DK056338, which funds the Texas Medical Center Digestive Diseases Center and its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institute of Diabetes and Digestive and Kidney Diseases or the NIH. JP Arab and VH Shah were supported by NIH/NIDDK P30DK084567 which funds Mayo Center for Cell Signaling in Gastroenterology and the contents of this project are solely the responsibility of the authors and do not necessarily represent the official views of the National Institute of Diabetes and Digestive and Kidney Diseases or the NIH. C Coarfa was partially supported by Cancer Prevention and Research Institute of Texas (CPRIT) awards RP170295 and RP170005, and by the NIH/NIDDK award R01DK111522 and the contents of this project are solely the responsibility of the authors and do not necessarily represent the official views of the National Institute of Diabetes and Digestive and Kidney Diseases or the NIH. AR Opekun was partially supported by an unrestricted institutional grant from DR and GP Laws. The laboratory of N Putluri receives grant funding from Agilent Technologies to develop mass spectrometry-based biomarkers in cancer (grant number: 0300016016). The authors have no other rel37evant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript. Publisher Copyright: {\textcopyright} 2020 The authors.",
year = "2020",
doi = "10.2144/fsoa-2019-0124",
language = "English (US)",
volume = "6",
journal = "Future Science OA",
issn = "2056-5623",
publisher = "Future Medicine Ltd.",
number = "2",
}