1. Urinary metabolic profiling by 1H NMR spectroscopy in patients with cirrhosis may discriminate overt but not covert hepatic encephalopathy
- Author
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Sara Montagnese, Hamza El Hadi, Simon D. Taylor-Robinson, Roger Williams, Mark J. W. McPhail, I. Jane Cox, Manuela Villanova, Piero Amodio, Mary M.E. Crossey, and Wellcome Trust, UK
- Subjects
0301 basic medicine ,LIVER ,Cirrhosis ,Hepatic encephalopathy ,Hippurate ,Histidine ,Magnetic resonance spectroscopy ,Metabolic profiling ,Urinary biomarkers ,Biochemistry ,Neurology (clinical) ,Cellular and Molecular Neuroscience ,Gastroenterology ,DISEASE ,Liver disease ,chemistry.chemical_compound ,0302 clinical medicine ,Model for End-Stage Liver Disease ,HEPATOCELLULAR-CARCINOMA ,MAGNETIC-RESONANCE ,EEG ,medicine.diagnostic_test ,Hepatocellular carcinoma ,TESTS ,030211 gastroenterology & hepatology ,Life Sciences & Biomedicine ,NUTRITIONAL-STATUS ,medicine.medical_specialty ,Urinary system ,Clinical Neurology ,VALIDATION ,Endocrinology & Metabolism ,03 medical and health sciences ,SYSTEMS ,Internal medicine ,medicine ,Creatinine ,Science & Technology ,Neurology & Neurosurgery ,business.industry ,Neurosciences ,METABONOMICS ,1103 Clinical Sciences ,Magnetic resonance imaging ,medicine.disease ,030104 developmental biology ,Endocrinology ,chemistry ,Neurosciences & Neurology ,1109 Neurosciences ,business - 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 (1H-NMR) 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.
- Published
- 2016
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