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Multivariate metabotyping of plasma predicts survival in patients with decompensated cirrhosis.
- Source :
-
Journal of hepatology [J Hepatol] 2016 May; Vol. 64 (5), pp. 1058-1067. Date of Electronic Publication: 2016 Jan 18. - Publication Year :
- 2016
-
Abstract
- Background & Aims: Predicting survival in decompensated cirrhosis (DC) is important in decision making for liver transplantation and resource allocation. We investigated whether high-resolution metabolic profiling can determine a metabolic phenotype associated with 90-day survival.<br />Methods: Two hundred and forty-eight subjects underwent plasma metabotyping by (1)H nuclear magnetic resonance (NMR) spectroscopy and reversed-phase ultra-performance liquid chromatography coupled to time-of-flight mass spectrometry (UPLC-TOF-MS; DC: 80-derivation set, 101-validation; stable cirrhosis (CLD) 20 and 47 healthy controls (HC)).<br />Results: (1)H NMR metabotyping accurately discriminated between surviving and non-surviving patients with DC. The NMR plasma profiles of non-survivors were attributed to reduced phosphatidylcholines and lipid resonances, with increased lactate, tyrosine, methionine and phenylalanine signal intensities. This was confirmed on external validation (area under the receiver operating curve [AUROC]=0.96 (95% CI 0.90-1.00, sensitivity 98%, specificity 89%). UPLC-TOF-MS confirmed that lysophosphatidylcholines and phosphatidylcholines [LPC/PC] were downregulated in non-survivors (UPLC-TOF-MS profiles AUROC of 0.94 (95% CI 0.89-0.98, sensitivity 100%, specificity 85% [positive ion detection])). LPC concentrations negatively correlated with circulating markers of cell death (M30 and M65) levels in DC. Histological examination of liver tissue from DC patients confirmed increased hepatocyte cell death compared to controls. Cross liver sampling at time of liver transplantation demonstrated that hepatic endothelial beds are a source of increased circulating total cytokeratin-18 in DC.<br />Conclusion: Plasma metabotyping accurately predicts mortality in DC. LPC and amino acid dysregulation is associated with increased mortality and severity of disease reflecting hepatocyte cell death.<br /> (Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)
- Subjects :
- Adult
Aged
Biomarkers blood
Biopsy
Cell Death
Female
Follow-Up Studies
Humans
Immunohistochemistry
Liver metabolism
Liver Cirrhosis mortality
Liver Cirrhosis pathology
Male
Middle Aged
Retrospective Studies
Survival Rate trends
Time Factors
United Kingdom epidemiology
Young Adult
Cytokines blood
Liver pathology
Liver Cirrhosis blood
Metabolomics methods
Subjects
Details
- Language :
- English
- ISSN :
- 1600-0641
- Volume :
- 64
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of hepatology
- Publication Type :
- Academic Journal
- Accession number :
- 26795831
- Full Text :
- https://doi.org/10.1016/j.jhep.2016.01.003