Introduction
Metabolomics
Metabolomics platforms
Data handling
Cirrhosis: potential biomarkers
Diagnostic markers of cirrhosis and progressive disease
Reference | Sample type | Application | Important metabolites reported | Analytical platform used | |
---|---|---|---|---|---|
Increased | Decreased | ||||
Yoo et al. (2019) [31] | Serum | Differentiation between patient with cirrhosis and healthy control | Phenylalanine, tyrosine, and tryptophan, palmitoylcarnitine and oleoylcarnitine, palmitic acid (C16:0), LPC (16:0, 18:2, and 22:6), | Myristic acid (C14:0), a-linolenic acid a (C18:3) and its downstream -3 PUFA metabolites, including and eicosapentaenoic acid (C20:5), leukotriene B4 and 5-HETE, LPA (16:0 and 18:1) | Untargeted LC-MS |
Zheng et al. (2017) [32] | Serum | Identification of potential metabolites associated with devolvement of cirrhosis in HBV | Acetate, pyruvate, and glutamine | Formate | NMR |
Xie et al. (2020) [33•] | Serum | Identification of biomarkers associated with stages of cirrhosis in patients with chronic liver disease | Taurocholate, tyrosine | Valine, linoelaidic acid | Targeted LC-MS |
Salguero et al. (2020) [34] | Plasma | Identification of metabolites associated with advanced cirrhosis. | Fatty acids, bile acids, aromatic and sulphur amino acids, butyrate derivatives, oxidised phospholipids, energy-related metabolites and bacterial fermentation–related metabolites | LPC and LPE, BCAA and metabolites of tricarboxylic acid cycle, among others | GC-MS, LC-MS |
Cano et al. (2017) [35] | Serum | Discriminate different stages of liver cirrhosis | taurochenodeoxycholate, taurocholate, glycocholate, tyrosine and PC (16:0/16:0) phosphatidylcholine | LC-MS | |
Liu et al. (2018) [36•] | Serum | Identification of specific bile acids and their contribution in cirrhosis | TCA, TCDCA, TUDCA, GCA, UDCA, CDCA, CA, TLCA, TDCA, HDCA and LCA. | Targeted LC-MS | |
Shao et al. (2018) [37] | Urine | association between gut microbiota and their metabolites vs cirrhosis | N6-methyladnosine, 1-methyluric acid cinnamic acid, deconoylcarnitine and phenacetylglutamine | LC-MS | |
Adams et al. (2020) [38] | Serum | Investigate the link between gut microbiome, bile acid profile and liver fibrosis. | Serum bile acids mainly primary conjugated bile acids including GCA and secondary conjugated bile acids. Faecal bile acids mainly secondary unconjugated bile acids including DCA | LC-MS | |
McPhail et al. (2017) [39] | Urine | Identification of metabolites associated with hepatic encephalopathy in patient with cirrhosis | Histidine, citrate and creatinine | NMR | |
Mindikoglu et al. (2018) [40] | Plasma | Identify metabolites related to prognosis (focus is kidney disease in cirrhosis) | S-adenosylhomocysteine, glucuronate, trans-aconitate, 3-ureidopropionate, 3-(4-hydroxyphenyl) lactate, 3-methoxytyramine sulphate, arabitol/xylitol, N-formylmethionine, phenyllactate and 7-methylguanine | Untargeted LC-MS | |
Bajaj et al. (2019) [41] | Serum and urine | Characterise changes in serum and urine of patient with cirrhosis who develop HE, are hospitalised or die | Hospitalisation: top important cluster in serum include pyridines and pyrimidines, sugar acids, sugar alcohols, amino acids and sulphur amino acids HE: top important cluster include pyridines and pyrimidines, sugar acids, sugar alcohols, amino acids, phenylacetates, disaccharides. Mortality: top important cluster include pyridines, sugar acids, sugar alcohols, acidic amino acids, phenylacetates, disaccharides | Hospitalisation: top important cluster in serum include basic amino acids, saturated fatty acids, dicarboxylic acids, purines and adipates HE: top important cluster include basic amino acids, saturated fatty acids, dicarboxylic acids, purines and adipates Mortality: top important cluster include saturated and unsaturated fatty acids, purine nucleosides, basic and sulphur amino acids, dicarboxylic acids, and adipates | GC-MS |
Predicting poor outcome
ACLF: potential biomarkers
Reference | Application | Sample | Important metabolites reported | Analytical platform | |
---|---|---|---|---|---|
Increased | Decreased | ||||
Bajaj et al. (2020) [47] | To identify metabolites profile which can predict development of ACLF in high-risk patient with cirrhosis | Serum | Microbial metabolites such as aromatic compounds, secondary or sulphated bile acids, and benzoate, oestrogen metabolites | Untargeted LC-MS | |
Moreau et al. (2020) [48•] | To assess metabolomic profile associated with ACLF. | Serum | L-Saccharopine, pentose phosphate, orotidine, cystathionine, hexose alcohols, N-Acetyl-L-tryptophan, D-Galacturonic acid,4-acetamidobutanoic acid, hydroxyphenylacetic acids, hydroxy-3-methoxyphenylglycol sulphate, 2-Heptanone, phenyllactic acid, quinolinic acid | Untargeted LC-MS | |
López-Vicario et al. (2020) [49•] | Role of lipid mediators in ACLF | Plasma | HETE, DiHETrE, EKODE, 11,12-DiHETrE, HETrE, HOTrEc, LTE4, 11-keto-TXB2 and PGE1, PGF2a | Targeted LC-MS | |
Mucke et al. (2020) [50] | To identify whether S1P concentration is associated with disease severity in patients with different stages of end stage liver failure and mortality. | Serum | S1P | Targeted LC-MS |
HCC: potential biomarkers
Reference | Application | Sample | Important metabolites reported | Analytical platform used | |
---|---|---|---|---|---|
Increased | Decreased | ||||
Poto et al. (2017) [53∙] | To Identify biomarkers which distinguish between HC and HCC | Plasma | Valine, serine, isoleucine, alpha D-glucosamine 1-phosphate and linoleic acid | Untargeted and targeted GC-MS | |
Cotte et al. (2019) [54] | To investigate plasma phospholipids as possible prognostic biomarkers for HCC | Plasma | higher phosphatidylcholine (PC), sphingomyelin (SM) | LPC 20:4 and plasmalogen- phosphatidylethanolamine (pPE) | LC-MS |
Kim et al. (2019) [55] | To distinguish between patients with cirrhosis and HCC | Serum | Methionine, proline, ornithine | Pimelylcranitine and octanoylcarnitine | Untargeted GC-MS and Targeted LC-MS |
Liang et al. (2020) [56] | Estimating risk for HCC development in patient with cirrhosis | Plasma | Phenylalanine | Glutamine | NMR and LC-MS |
Luo et al. (2018) [57∙] | To identify metabolites for early HCC diagnosis | Serum | Glycocholate (GCA) | Phenylalanyl-tryptophan (Phe-Trp) | LC-MS |