Urinary metabolic profiling by 1H NMR spectroscopy in patients with cirrhosis may discriminate overt but not covert hepatic encephalopathy
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Type
Journal Article
Abstract
To date urinary metabolic profiling has been applied to define a specific metabolic fingerprint
of hepatocellular carcinoma on a background of cirrhosis. Its utility for the stratification of other
complications of cirrhosis, such as hepatic encephalopathy (HE), remains to be established. Urinary
proton nuclear magnetic resonance (1H-NMR) spectra were acquired and NMR data from 52 patients
with cirrhosis (35 male; 17 female, median (range) age [60 (18-81) years]) and 17 controls were
compared. A sub-set of 45 patients (33 male; 12 female, [60 (18-90) years, median model for end stage
liver disease (MELD) score 11 (7-27)]) were fully characterised by West-Haven criteria, Psychometric
Hepatic Encephalopathy Score (PHES) and electroencephalogram (EEG), and defined as overt HE
(OHE, n=21), covert HE (cHE, n=7) or no HE (n=17). Urinary proton nuclear magnetic resonance (1HNMR)
spectra were analysed by partial-least-squares discriminant analysis (PLS-DA). The results
showed good discrimination between patients with cirrhosis (n=52) and healthy controls (n=17)
(R2X=0.66, R2Y=0.47, Q2Y=0.31, sensitivity-60%, specificity-100%) as the cirrhosis group had
higher 1-methylnicotinamide with lower hippurate, acetate, phenylacetylglycine and N-methyl nicotinic
acid levels. While patients with OHE could be discriminated from those with no HE, with higher
histidine, citrate and creatinine levels, the best models lack robust validity (R2X=0.65, R2Y=0.48,
Q2Y=0.12, sensitivity-100%, specificity-64%) with the sample size used. Urinary 1H-NMR metabolic
profiling did not discriminate patients with cHE from those without HE, nor discriminate subjects on
the basis of PHES/EEG result or MELD score. In conclusion, patients with cirrhosis showed different
urinary 1H-NMR metabolic profiles compared to healthy controls and those with OHE may be
distinguished from those with no HE although larger studies are required. However, urinary 1H-NMR
metabolic profiling did not discriminate patients with differing grades of HE or according to severity
of underlying liver disease.
of hepatocellular carcinoma on a background of cirrhosis. Its utility for the stratification of other
complications of cirrhosis, such as hepatic encephalopathy (HE), remains to be established. Urinary
proton nuclear magnetic resonance (1H-NMR) spectra were acquired and NMR data from 52 patients
with cirrhosis (35 male; 17 female, median (range) age [60 (18-81) years]) and 17 controls were
compared. A sub-set of 45 patients (33 male; 12 female, [60 (18-90) years, median model for end stage
liver disease (MELD) score 11 (7-27)]) were fully characterised by West-Haven criteria, Psychometric
Hepatic Encephalopathy Score (PHES) and electroencephalogram (EEG), and defined as overt HE
(OHE, n=21), covert HE (cHE, n=7) or no HE (n=17). Urinary proton nuclear magnetic resonance (1HNMR)
spectra were analysed by partial-least-squares discriminant analysis (PLS-DA). The results
showed good discrimination between patients with cirrhosis (n=52) and healthy controls (n=17)
(R2X=0.66, R2Y=0.47, Q2Y=0.31, sensitivity-60%, specificity-100%) as the cirrhosis group had
higher 1-methylnicotinamide with lower hippurate, acetate, phenylacetylglycine and N-methyl nicotinic
acid levels. While patients with OHE could be discriminated from those with no HE, with higher
histidine, citrate and creatinine levels, the best models lack robust validity (R2X=0.65, R2Y=0.48,
Q2Y=0.12, sensitivity-100%, specificity-64%) with the sample size used. Urinary 1H-NMR metabolic
profiling did not discriminate patients with cHE from those without HE, nor discriminate subjects on
the basis of PHES/EEG result or MELD score. In conclusion, patients with cirrhosis showed different
urinary 1H-NMR metabolic profiles compared to healthy controls and those with OHE may be
distinguished from those with no HE although larger studies are required. However, urinary 1H-NMR
metabolic profiling did not discriminate patients with differing grades of HE or according to severity
of underlying liver disease.
Date Issued
2016-09-17
Date Acceptance
2016-09-01
Citation
Metabolic Brain Disease, 2016, 32 (2), pp.331-341
ISSN
1573-7365
Publisher
Springer Verlag (Germany)
Start Page
331
End Page
341
Journal / Book Title
Metabolic Brain Disease
Volume
32
Issue
2
Copyright Statement
© The Authors 2016. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
License URL
Sponsor
Wellcome Trust, UK
Subjects
Science & Technology
Life Sciences & Biomedicine
Endocrinology & Metabolism
Neurosciences
Neurosciences & Neurology
Hepatic encephalopathy
Metabolic profiling
Urinary biomarkers
Magnetic resonance spectroscopy
Hippurate
Histidine
HEPATOCELLULAR-CARCINOMA
MAGNETIC-RESONANCE
NUTRITIONAL-STATUS
METABONOMICS
VALIDATION
DISEASE
SYSTEMS
TESTS
LIVER
EEG
1103 Clinical Sciences
1109 Neurosciences
Neurology & Neurosurgery
Publication Status
Published