title: Metabolomic approach by 1H NMR spectroscopy of serum for the assessment of chronic liver failure in patients with cirrhosis.
abstract: Assessment of chronic liver failure (CLF) in cirrhotic patients is needed to make therapeutic decisions. A biological score is usually performed, using the Model for End-Stage Liver Disease (MELD), to evaluate CLF. Nevertheless, MELD does not take into account metabolic perturbations produced by liver-function impairment. In contrast, metabolomics can investigate many metabolic perturbations within biological systems. The purpose of this study was to assess whether metabolomic profiles of serum, obtained by proton NMR spectroscopy from cirrhotic patients, are affected by the severity of CLF. An orthogonal projection to latent-structure analysis was performed to compare MELD scores and NMR spectra of 124 patients with cirrhosis. The statistical model obtained showed a good explained variance (R(2)X = 0.87 and R(2)Y = 0.86) and a good predictability (Q(2)Y = 0.64). Metabolomic profiles showed significant differences regarding various metabolites depending of severity of CLF: levels of high-density lipoprotein and phosphocholine resonances were significantly higher in patients with mild CLF compared to severe CLF. Other metabolites such as lactate, pyruvate, glucose, amino acids, and creatinine were significantly higher in patients with severe CLF than mild CLF. Our conclusion is that metabolomic NMR analysis provides new insights into metabolic processes related to the severity of hepatic function impairment in cirrhosis.
authors.affiliation: Laboratoire CSPBAT, UMR 7244, Université Paris 13, Equipe Spectroscopie Biomolécules et Milieux Biologiques, Avenue Marcel Cachin, Bobigny 93000, France. roland.amathieu@jvr.aphp.fr
authors.forename: Roland
authors.initials: R
authors.lastname: Amathieu
authors.forename: Pierre
authors.initials: P
authors.lastname: Nahon
authors.forename: Mohamed
authors.initials: M
authors.lastname: Triba
authors.forename: Nadia
authors.initials: N
authors.lastname: Bouchemal
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Trinchet
authors.forename: Michel
authors.initials: M
authors.lastname: Beaugrand
authors.forename: Gilles
authors.initials: G
authors.lastname: Dhonneur
authors.forename: Laurence
authors.initials: L
authors.lastname: Le Moyec
mesh_terms: D058625:End Stage Liver Disease / Q000097:blood* / Q000209:etiology / Q000473:pathology; D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008103:Liver Cirrhosis / Q000097:blood* / Q000150:complications / Q000473:pathology; D008111:Liver Function Tests; D009682:Magnetic Resonance Spectroscopy / Q000379:methods* / Q000706:statistics & numerical data; D008297:Male; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D015233:Models, Statistical; D011379:Prognosis; D012372:ROC Curve; D012107:Research Design; D044967:Serum / Q000737:chemistry*; D012720:Severity of Illness Index