Serum 1H-NMR metabolomic fingerprints of acute-on-chronic liver failure in intensive care unit patients with alcoholic cirrhosis

Roland Amathieu (1, 2) , Mohamed N Triba (2) , Pierre Nahon (3) , Nadine Bouchemal (2) , Walid Kamoun (1) , Hakim Haouache (1) , Jean-Claude Trinchet (3) , Philippe Savarin (2) , Laurence Le Moyec (4) , Gilles Dhonneur (1)

1 Service d'Anesthésie et des Réanimations Chirurgicales
2 CSPBAT - Chimie, Structures et Propriétés de Biomatériaux et d'Agents Thérapeutiques
3 Hôpital Jean Verdier [AP-HP]
4 UBIAE - Unité de biologie intégrative des adaptations à l'exercice

Introduction Acute-on-chronic liver failure is characterized by acute deterioration of liver function in patients with compensated or decompensated, but stable, cirrhosis. However, there is no accurate definition of acute-on-chronic liver failure and physicians often use this term to describe different clinical entities. Metabolomics investigates metabolic changes in biological systems and identifies the biomarkers or metabolic profiles. Our study assessed the metabolomic profile of serum using proton nuclear magnetic resonance (1H-NMR) spectroscopy to identify metabolic changes related to acute-on-chronic liver failure. Patients Ninety-three patients with compensated or decompensated cirrhosis (CLF group) but stable liver function and 30 patients with cirrhosis and hospitalized for the management of an acute event who may be responsible of acute-on-chronic liver failure (ACLF group), were fully analyzed. Blood samples were drawn at admission, and sera were separated and stored at -80°C until 1H-NMR spectral analysis. Using orthogonal projection to latent-structure discriminant analyses, various metabolites contribute to the complete separation between these both groups. Results The predictability of the model was 0.73 (Q2Y) and the explained variance was 0.63 (R2Y). The main metabolites that had increased signals related to acute-on-chronic liver failure were lactate, pyruvate, ketone bodies, glutamine, phenylalanine, tyrosine, and creatinine. High-density lipids were lower in the ALCF group than in CLF group. Conclusion A serum metabolite fingerprint for acute-on-chronic liver failure, obtained with 1H-NMR, was identified. Metabolomic profiling may aid clinical evaluation of patients with cirrhosis admitted into intensive care units with acute-on-chronic liver failure, and provide new insights into the metabolic processes involved in acute impairment of hepatic function.

Keywords: Biological Markers; Creatinine; Glutamine; high density lipoprotein; ketone body; acute on chronic liver failure; adult; alcohol liver cirrhosis; amino acid blood level; article; blood level; blood sampling; blood storage; controlled study; creatinine blood level; critically ill patient; cryopreservation; decompensated liver cirrhosis; discriminant analysis; female; glutamine blood level; hospitalization; human; intensive care unit; ketone body blood level; lactate blood level; lipoprotein blood level; liver function; major clinical study; male; metabolomics; proton nuclear magnetic resonance; pyruvate blood level; Humans; Intensive Care Units; Ketone Bodies; Lactic Acid; Liver Cirrhosis; Alcoholic; Liver Failure; Acute; Magnetic Resonance Spectroscopy; Metabolome; Multivariate Analysis; Phenylalanine; Pyruvic Acid; Tyrosine

Domains: Life Sciences [q-bio]

Roland Amathieu, Mohamed N Triba, Pierre Nahon, Nadine Bouchemal, Walid Kamoun, et al.. Serum 1H-NMR metabolomic fingerprints of acute-on-chronic liver failure in intensive care unit patients with alcoholic cirrhosis. PLoS ONE, 2014, 9 (2), pp.e89230. ⟨10.1371/journal.pone.0089230⟩. ⟨hal-02489938⟩