Plasma Amino Acid Concentrations Predict Mortality in Patients with End-Stage Liver Disease

Abstract

BackgroundThe 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.Methods166 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.Results33/166 (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.ConclusionsAmino 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.

Serum Metabonomics Analysis of Liver Failure Treated by Nonbioartificial Liver Support Systems

“…The liver plays a key role in amino acid metabolism [ 23 ], liver injury can cause imbalance of amino acid metabolism and change of amino acid levels in human body [ 24 , 25 ]. Phenylalanine is an essential amino acid, it can synthesize proteins and be converted into nonessential amino acid tyrosine.…”

Assessment of Malnutrition, Sarcopenia and Frailty in Patients with Cirrhosis: Which Tools Should We Use in Clinical Practice?

“…This ratio increases as the liver disease progresses and is predictive of survival and other major complications such as hepatic encephalopathy [97]. Decreased values of valine, Fischer ratio and increased rate of phenylalanine and tyrosine were associated with mortality, with a significant correlation with MELD and MELD-Na [98]. The presence of an altered amino-acid ratio was also associated with a reduction in the serum albumin concentration in the following year [99].…”

Increased plasma proline concentrations are associated with sarcopenia in the elderly

“…Amino acid profiling and metabolome analysis using mass spectrometry have been powerful analytical tools [ 7 ] for revealed associations between plasma amino acid profiles and various diseases, including cancer [ 8 – 10 ], obesity and glucose metabolism [ 11 – 14 ], end-stage liver disease [ 15 ], inflammatory bowel disease [ 16 ], depression [ 17 ], rheumatoid arthritis [ 18 ], acute dissecting aortic aneurysm [ 19 ], and aging and longevity [ 20 , 21 ]. Understanding changes in amino acid profiles may therefore be useful for early diagnosis and insight into the pathophysiological mechanisms underlying such diseases.…”