title: Urinary metabolic profiling by1H NMR spectroscopy in patients with cirrhosis may discriminate overt but not covert hepatic encephalopathy.
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. Urinary1H-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 urinary1H-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, urinary1H-NMR metabolic profiling did not discriminate patients with differing grades of HE or according to severity of underlying liver disease.
authors.affiliation: Liver Unit, Division of Digestive Health, Department of Surgery and Cancer, Imperial College London, St Mary's Campus, London, W2 1NY, UK.
authors.forename: Mark J W
authors.initials: MJ
authors.lastname: McPhail
authors.affiliation: Department of Medicine DIMED, University of Padova, Padova, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Montagnese
authors.affiliation: Department of Medicine DIMED, University of Padova, Padova, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Villanova
authors.affiliation: Department of Medicine DIMED, University of Padova, Padova, Italy.
authors.forename: Hamza
authors.initials: H
authors.lastname: El Hadi
authors.affiliation: Department of Medicine DIMED, University of Padova, Padova, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Amodio
authors.affiliation: Liver Unit, Division of Digestive Health, Department of Surgery and Cancer, Imperial College London, St Mary's Campus, London, W2 1NY, UK.
authors.forename: Mary M E
authors.initials: MM
authors.lastname: Crossey
authors.affiliation: Institute of Hepatology London, Foundation for Liver Research, 111 Coldharbour Lane, London, SE5 9NT, UK.|Faculty of Life Sciences & Medicine, King's College London, London, UK.
authors.forename: Roger
authors.initials: R
authors.lastname: Williams
authors.affiliation: Institute of Hepatology London, Foundation for Liver Research, 111 Coldharbour Lane, London, SE5 9NT, UK. j.cox@researchinliver.org.uk.|Faculty of Life Sciences & Medicine, King's College London, London, UK. j.cox@researchinliver.org.uk.
authors.forename: I Jane
authors.initials: IJ
authors.lastname: Cox
authors.affiliation: Liver Unit, Division of Digestive Health, Department of Surgery and Cancer, Imperial College London, St Mary's Campus, London, W2 1NY, UK.
authors.forename: Simon D
authors.initials: SD
authors.lastname: Taylor-Robinson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003937:Diagnosis, Differential; D004569:Electroencephalography; D058625:End Stage Liver Disease / Q000652:urine; D005260:Female; D006501:Hepatic Encephalopathy / Q000523:psychology / Q000652:urine*; D006626:Hippurates / Q000652:urine; D006639:Histidine / Q000652:urine; D006801:Humans; D008103:Liver Cirrhosis / Q000652:urine*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D009752:Nutritional Status; D011569:Psychiatric Status Rating Scales; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D006626:Hippurates; D006639:Histidine; C030514:hippuric acid
keywords: Hepatic encephalopathy; Hippurate; Histidine; Magnetic resonance spectroscopy; Metabolic profiling; Urinary biomarkers