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.
Highlights
The human liver is crucial to metabolic processes
Valine concentrations and constellations composed of branched-chain and aromatic amino acids were strongly associated with prognosis
Already in 1971, Fischer et al presented data indicating that low levels of the ratio between the structurally related branched-chain amino acids (BCAA) valine, leucine and isoleucine and the structurally related aromatic amino acids (AAA) phenylalanine, tyrosine and tryptophan (BCAA / AAA, Fischer’s ratio) promote hepatic encephalopathy in cirrhotic patients [3,4]
Summary
The human liver is crucial to metabolic processes. Imbalances in amino acid metabolism and alterations of amino acid levels in human blood due to liver diseases are described in existing literature [1,2]. Changes in amino acid levels in blood affect a large number of different metabolic pathways, but to our knowledge until now there is no study available investigating the complex relationship between plasma amino acid concentrations and prognosis in patients with end-stage liver disease. The MELD scoring system has replaced the ChildPugh-Turcotte based classification for listing in UNOS (United Network of Organ Sharing) area in 2002. It was introduced into the Eurotransplant community in 2006. 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
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