Urinary metabolic profiling by 1H 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. 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.

• Authors: Mark J W McPhail, Sara Montagnese, Manuela Villanova, Hamza El Hadi, Piero Amodio, Mary M E Crossey, Roger Williams, I Jane Cox, Simon D Taylor-Robinson
• Journal: Metabolic brain disease (Metab Brain Dis) Vol. 32 Issue 2 Pg. 331-341 (04 2017) ISSN: 1573-7365 [Electronic] United States
• PMID: 27638475 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Hippurates
• Histidine
• hippuric acid

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Diagnosis, Differential
• Electroencephalography
• End Stage Liver Disease (urine)
• Female
• Hepatic Encephalopathy (psychology, urine)
• Hippurates (urine)
• Histidine (urine)
• Humans
• Liver Cirrhosis (urine)
• Magnetic Resonance Spectroscopy
• Male
• Middle Aged
• Neuropsychological Tests
• Nutritional Status
• Psychiatric Status Rating Scales
• Sensitivity and Specificity
• Young Adult