1H nuclear magnetic resonance spectroscopy-based metabonomic study in patients with cirrhosis and hepatic encephalopathy

Table 1 Patients and controls were well matched for age and sex

	Controls	Cirrhosis	Encephalopathy
Age	48.8 ± 9.9	54.3 ± 8.8	56.8 ± 6.0
Sex	M: 10	M: 9	M: 12
	F: 7	F: 9	F: 6
CP score	N/A	7.8 ± 1.6	9.9 ± 2.1
Child class a	N/A	1	1
Child class b	N/A	11	6
Child class c	N/A	6	11

Patients with hepatic encephalopathy had more severe liver disease. CP: Child-Pugh; M: Male; F: Female.

Table 2 Results for ketone bodies, branch chain and aromatic amino acids are shown

	Chemical shift	Cirrhosis	Encephalopathy	Controls
Acetoacetate	2.29	0.23 ± 0.02b	0.41 ± 0.05b	0.05 ± 0.00
Β-hydroxybutyr	2.31	0.58 ± 0.14b	0.16 ± 0.02b	0.08 ± 0.00
Leucine	0.96	0.33 ± 0.02	0.49 ± 0.05b	0.35 ± 0.02
Isoleucine	1.01	0.12 ± 0.02	0.27 ± 0.02b	0.13 ± 0.02
Valine	1.04	0.14 ± 0.01d	0.16 ± 0.02d	0.36 ± 0.03
Phenylalanine	7.38	0.08 ± 0.01b	0.06 ± 0.02b	0.02 ± 0.01
Tyrosine	6.91	0.23 ± 0.02b	0.25 ± 0.06b	0.07 ± 0.00
Methionine	2.14	0.07 ± 0.02b	0.08 ± 0.02b	0.03 ± 0.01

Acetoacetate and β-hydroxybutyrate concentrations were significantly higher in patients than controls (^bP < 0.01 in all cases). Aromatic amino acids concentrations were significantly higher in patients than controls (P < 0.01 in all cases). Valine concentrations were significantly lower in patients than controls (^dP < 0.01). Leucine was significantly higher if we compared encephalopathics with controls (^bP < 0.01), but there was no difference if we compared cirrhotics and controls. Isoleucine was significantly lower if we compared encephalopathics with controls (^bP < 0.01) but there was no difference between cirrhotics and controls.

Table 3 Results for glycolysis end products and gluconeogenetic precursors are shown

	Chemical shift	Cirrhosis	Encephalopathy	Controls
Lactate	1.33	1.53 ± 0.11b	1.41 ± 0.13b	0.42 ± 0.05
Pyruvate	2.38	0.11 ± 0.02b	0.17 ± 0.02b	0.03 ± 0.00
Alanine	1.48	0.77 ± 0.04b	0.73 ± 0.06b	0.61 ± 0.05
Threonine	1.34	0.39 ± 0.02b	0.25 ± 0.01b	0.08 ± 0.1
Glycine	3.57	0.31 ± 0.03b	0.18 ± 0.01b	0.09 ± 0.1
Aspartate	2.82	0.37 ± 0.03b	0.27 ± 0.02b	0.03 ± 0.1

Lactate, pyruvate, alanine, threonine, glycine and aspartate concentrations were all significantly higher in patients than controls (^bP < 0.01 in all cases).

Table 4 Results for urea cycle intermediates are shown

	Chemical shift	Cirrhosis	Encephalopathy	Controls
Glutamine	2.46	0.44 ± 0.08b	0.36 ± 0.04b	0.63 ± 0.03
Glutamate	2.36	1.36 ± 0.25d	0.84 ± 0.16a	0.58 ± 0.04
Histidine	7.83	0.16 ± 0.01b	0.18 ± 0.02b	0.36 ± 0.04
Arginine	1.93	0.08 ± 0.01b	0.1 ± 0.01b	0.14 ± 0.02

Glutamine, histidine and arginine concentrations were significantly lower in patients than controls (^bP < 0.01 in all cases). Glutamate concentrations were significantly higher in cirrhotics (^dP < 0.01) compared to controls. It was also significantly increased if we compared encephalopathics with controls (^aP < 0.05).

Table 5 Results for amines, glycerol and myo-inositol are shown

	Chemical shift	Cirrhotics	Encephalopathics	Controls
Methylamine	2.54	0.17 ± 0.03	0.19 ± 0.03	0
Dimethylamine	2.72	0.29 ± 0.03	0.31 ± 0.04	0
Tmao	3.27	0.45 ± 0.07	0.51 ± 0.08	0
Glycerol	3.79	0.53 ± 0.09b	0.2 ± 0.02b	0.08 ± 0.02
Myoinositol	3.63	0.37 ± 0.06a	0.19 ± 0.04	0.16 ± 0.03

Methylamine, dimethylamine and TMAO were present in patients and absent in controls. Glycerol concentrations were significantly higher in patients than controls (^bP < 0.01). Myo-inositol concentrations were significantly higher in cirrhotics (^aP < 0.015) but there were no differences between encephalopathics and controls.