title: Plasma Amino Acid Concentrations Predict Mortality in Patients with End-Stage Liver Disease.
abstract: BACKGROUND
  The liver plays a key role in amino acid metabolism. In former studies, a ratio between branched-chain and aromatic amino acids (Fischer's ratio) revealed associations with hepatic encephalopathy. Furthermore, low concentrations of branched-chain amino acids were linked to sarcopenia in literature. Encephalopathy and sarcopenia are known to dramatically worsen the prognosis. Aim of this study was to investigate a complex panel of plasma amino acids in the context of mortality in patients with end-stage liver disease.
  
  
  METHODS
  166 patients evaluated for orthotopic liver transplantation were included. 19 amino acids were measured from citrated plasma samples using mass spectrometry. We performed survival analysis for plasma amino acid constellations and examined the relationship to established mortality predictors.
  
  
  RESULTS
  33/166 (19.9%) patients died during follow-up. Lower values of valine (p<0.001), Fischer's ratio (p<0.001) and valine to phenylalanine ratio (p<0.001) and higher values of phenylalanine (p<0.05) and tyrosine (p<0.05) were significantly associated with mortality. When divided in three groups, the tertiles discriminated cumulative survival for valine (p = 0.016), phenylalanine (p = 0.024) and in particular for valine to phenylalanine ratio (p = 0.003) and Fischer's ratio (p = 0.005). Parameters were also significantly correlated with MELD and MELD-Na score.
  
  
  CONCLUSIONS
  Amino acids in plasma are valuable biomarkers to determine increased risk of mortality in patients with end-stage liver disease. In particular, valine concentrations and constellations composed of branched-chain and aromatic amino acids were strongly associated with prognosis. Due to their pathophysiological importance, the identified amino acids could be used to examine individual dietary recommendations to serve as potential therapeutic targets.
authors.affiliation: Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Leipzig, Germany.
authors.forename: Benedict
authors.initials: B
authors.lastname: Kinny-Köster
authors.affiliation: Department of Visceral, Vascular, Thoracic and Transplant Surgery, University Hospital Leipzig, Leipzig, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Bartels
authors.affiliation: Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Leipzig, Germany.|LIFE - Leipzig Research Center for Civilization Diseases, University Hospital Leipzig, Leipzig, Germany.
authors.forename: Susen
authors.initials: S
authors.lastname: Becker
authors.affiliation: LIFE - Leipzig Research Center for Civilization Diseases, University Hospital Leipzig, Leipzig, Germany.|Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Scholz
authors.affiliation: Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Leipzig, Germany.|LIFE - Leipzig Research Center for Civilization Diseases, University Hospital Leipzig, Leipzig, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Thiery
authors.affiliation: Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Leipzig, Germany.|LIFE - Leipzig Research Center for Civilization Diseases, University Hospital Leipzig, Leipzig, Germany.
authors.forename: Uta
authors.initials: U
authors.lastname: Ceglarek
authors.affiliation: Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Leipzig, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Kaiser
mesh_terms: D024322:Amino Acids, Aromatic / Q000097:blood* / Q000378:metabolism; D000597:Amino Acids, Branched-Chain / Q000097:blood* / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D058625:End Stage Liver Disease / Q000097:blood* / Q000401:mortality; D005260:Female; D006501:Hepatic Encephalopathy / Q000097:blood* / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D016031:Liver Transplantation; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D055948:Sarcopenia / Q000097:blood*
chemical_list: D024322:Amino Acids, Aromatic; D000597:Amino Acids, Branched-Chain; D015415:Biomarkers