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

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

Research output: Contribution to journalArticle

1 Scopus citations

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.

Original languageEnglish (US)
JournalFuture Science OA
Volume6
Issue number2
DOIs
StatePublished - 2020

Keywords

  • MELD-Na score
  • biomarker
  • cirrhosis
  • liver transplantation
  • metabolite
  • metabolomics
  • mortality
  • myo-inositol
  • primary biliary cholangitis
  • primary sclerosing cholangitis

ASJC Scopus subject areas

  • Biotechnology

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    Mindikoglu, A. L., Coarfa, C., Opekun, A. R., Shah, V. H., Arab, J. P., Lazaridis, K. N., Putluri, N., Ambati, C. R., Robertson, M. J., Devaraj, S., Jalal, P. K., Rana, A., Goss, J. A., Dowling, T. C., Weir, M. R., Seliger, S. L., Raufman, J. P., Bernard, D. W., & Vierling, J. M. (2020). Metabolomic biomarkers are associated with mortality in patients with cirrhosis caused by primary biliary cholangitis or primary sclerosing cholangitis. Future Science OA, 6(2). https://doi.org/10.2144/fsoa-2019-0124