Table 3.
Summary of metabolomic studies examining the development of hepatic fibrosis and cirrhosis
| species [ref] | tissue | platform | up-regulated | down-regulated | conclusions |
|---|---|---|---|---|---|
| Human [63 HV; 36 LC] [27] |
serum | NMR | Acetate, pyruvate, glutamine, "N-acetylglycoproteins", 2-oxoglutarate, taurine, glycerol, tyrosine, 1-methylhistidine, phenylalanine | LDL, VLDL, leucine, isoleucine, valine, acetoacetate, choline, unsaturated lipid | Downregulation of essential amino acids suggests depressed protein turnover. |
| Human [16 HV; 25 LC] [28] |
serum | GCxGC- TOFMS |
D-Alanine, D-proline | L-Alanine, L-valine, L-isoleucine, L-leucine, L-serine, L-asparagine | Targeted amino acid analysis reveals loss of ability by the cirrhotic liver to metabolize D-amino acids |
| Human [22 HV; 18 LC (alcohol); 19 LC (HBV) [29] |
serum | UPLC-ESI- QTOFMS |
GCDCA, GCA, L-acetylcarnitine, myristamide, oleamide (only in alcohol cirrhosis) | LPC(16:0), LPC(18:2), LPC(18:0), LPC(20:3), LPC(20:5) myristamide, oleamide (only in HBV cirrhosis) | Pattern very similar to NASH and so NASH signature dominates serum picture in cirrhosis, irrespective of origin as alcohol or HBV. |
| Human [HV and LC (HBV)] [30] |
serum | LCMS | GCDCA | LPCs | Confirmatory of bile acid and phospholipid perturbations. |
| Human [30 HV; 30 LC (compensated); 30 LC (decompensated) [31] |
serum | NMR | - | In both compensated and decompensated LC: isoleucine, valine | Many other changes recorded, but with OPLS-DA correlations <0.85 |
| Human [30 HV; 30 CHB; 30 LC] [32] |
serum | LCMS | Relative to HV: 16:1-carnitine, 18:1-carnitine | Relative to HV: carnitine, pimeloylcarnitine Also relative to CHB: PE(22:6/16:0), PE(20:4/18:0) | Elevation of two MUFA-carnitines suggests reduced β-oxidation of these two fatty acids. |
| Human [24 HV; 17 LC] [34] |
faeces | UPLC-ESI- QTOFMS |
LPC(16:0), LPC(18:0), LPC(18:1), LPC(18:2) | CDCA, 7-ketolithocholic acid, urobilin, urobilinogen | Increased LPCs in faeces consistent with lower serum LPCs in LC. Biliary excretion of bile acids known to be reduced in LC |
| Human [57 non-LC; 11 LC] [33] | liver | NMR | UFA, phosphocholine, glutamate, phosphoethanolamine | Choline, TMAO, α-glucose, glutamine, aspartate, β-glucose | Shift from glutamine and glucose to glutamate suggests a net release of ammonium and impaired ammonium detoxication. |
| Rat treated with CCl4, then with Xia Yu Xue Decoction [25] | urine | GCMS | Apart from propionate and leucine, all changes due to CCl4 were reversed by Xia Yu Xue Decoction. | Effect of CCl4: Propionate, benzoate, leucine, octanoate, phenol, glycine, indole, oleic acid, lysine | Some metabolic changes of uncertain origin that may be associated with fibrosis |
| Rat treated with CCl4 [26] | urine | UPLC-ESI- QTOFMS |
Glycocholate | Hard to evaluate in this model if GCA is really a marker for fibrosis | |
| Rat treated with thioacetamide [22] | liver | NMR | Lactate, choline, proline, "glutamine/glutamate" | TMA, glycogen, inosine, fumarate | Raw data very poor and these NMR findings have uncertain validity |
Abbreviations used: LC, liver cirrhosis; CHB, chronic hepatitis B; TMA, trimethylamine; CCl4, carbon tetrachloride; UFA, unsaturated fatty acid units (-CH=CH-CH2-). GCxGC-TOFMS, Two-dimensional gas chromatography time-of-flight mass spectrometry. OPLS-DA, orthogonal partial least squares projection to latent structures-discriminant analysis, PE, phosphatidylethanolamine. For other abbreviations, see footnotes to Table 1