Imperial College London
Portrait Picture

Dr Evangelos Triantafyllou

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Lecturer in Liver Immunology
 
 
 
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Contact

 

e.triantafyllou Website

 
 
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Location

 

10.N12ACommonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{McPhail:2016:10.1016/j.jhep.2016.01.003,
author = {McPhail, MJW and Shawcross, D and Lewis, MR and Coltart, I and Want, E and Veselkov, K and Abeles, RD and Kyriakides, M and Pop, O and Triantafyllou, E and Antoniades, CG and Quaglia, A and Bernal, W and Auzinger, G and Coen, M and Nicholson, J and Wendon, JA and Holmes, E and Taylor-Robinson, SD and Jassem, W and O'Grady, J and Heaton, N},
doi = {10.1016/j.jhep.2016.01.003},
journal = {Journal of Hepatology},
pages = {1058--1067},
title = {Mutlivariate metabotyping of plasma accurately predicts survival in decompensated cirrhosis},
url = {http://dx.doi.org/10.1016/j.jhep.2016.01.003},
volume = {64},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background & AimsPredicting 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.MethodsTwo hundred and forty-eight subjects underwent plasma metabotyping by 1H 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)).Results1H 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.ConclusionPlasma metabotyping accurately predicts mortality in DC. LPC and amino acid dysregulation is associated with increased mortality and severity of disease reflecting hepatocyte cell death.
AU  - McPhail,MJW
AU  - Shawcross,D
AU  - Lewis,MR
AU  - Coltart,I
AU  - Want,E
AU  - Veselkov,K
AU  - Abeles,RD
AU  - Kyriakides,M
AU  - Pop,O
AU  - Triantafyllou,E
AU  - Antoniades,CG
AU  - Quaglia,A
AU  - Bernal,W
AU  - Auzinger,G
AU  - Coen,M
AU  - Nicholson,J
AU  - Wendon,JA
AU  - Holmes,E
AU  - Taylor-Robinson,SD
AU  - Jassem,W
AU  - O'Grady,J
AU  - Heaton,N
DO  - 10.1016/j.jhep.2016.01.003
EP  - 1067
PY  - 2016///
SN  - 1600-0641
SP  - 1058
TI  - Mutlivariate metabotyping of plasma accurately predicts survival in decompensated cirrhosis
T2  - Journal of Hepatology
UR  - http://dx.doi.org/10.1016/j.jhep.2016.01.003
UR  - http://hdl.handle.net/10044/1/29194
VL  - 64
ER  -
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