Dynamic elevation of aromatic amino acids in Hepatitis C Virus induced cirrhosis after a standard meal

Kareen L. Hill, James A. Haddad, Rabab O. Ali, Grace Y. Zhang, Gabriella M. Quinn, Elizabeth Townsend, Gregory T. Everson, Steve M. Helmke, Mohammadhadi Bagheri, Megan Schoenfeld, Shanna Yang, Christopher Koh, Elliot B. Levy, David E. Kleiner, David B. Sacks, Ohad Etzion, Theo Heller

Research output: Contribution to journalArticlepeer-review

Abstract

Background & Aims: Perturbations in aromatic (AAA) and branched-chain amino acids (BCAA) are seen in decompensated liver disease. The aim of this study was to evaluate the dynamic, post-prandial relationship between hepatitis C virus (HCV) induced liver disease and amino acid concentrations in patients with compensated liver disease. Methods: HCV-infected patients underwent a baseline liver biopsy to determine Ishak Fibrosis and evaluate the liver transcriptome. Patients ate a standard meal and underwent peripheral vein sampling at defined intervals. Quantitative analysis of amino acids was preformed using liquid chromatography-tandem mass spectrometry. Results: At baseline there was no difference in AAA and BCAA concentrations between cirrhotic and non-cirrhotic patients. After a standard meal, AAA, but not BCAA, were elevated in cirrhotic patients compared to non-cirrhotic at every time point. The Hepquant shunt fraction was significantly higher in cirrhotic patients and positively correlated with AAA at all time points, but not BCAA. Analysis of the hepatic transcriptome demonstrated greater downregulation of the AAA degradation pathways than the BCAA degradation pathways. Conclusion: At baseline cirrhotic patients with compensated liver disease have adequate reserve liver function to metabolize AAA and BCAA. When faced with a metabolic stressor, such as a standard meal, cirrhotic patients are less able to metabolize the increased load of AAA. This impairment correlates with porto-systemic shunting. Further evaluation of AAA in compensated liver disease might further the understanding of the liver-muscle- axis and the role it may play in development of sarcopenia in liver disease.

Original languageEnglish
JournalClinical and Translational Gastroenterology
DOIs
StateAccepted/In press - 1 Jan 2023
Externally publishedYes

Keywords

  • Amino Acids
  • Aromatic Amino Acids
  • Branched-chain amino acids
  • Cirrhosis
  • Hepatitis C
  • sarcopenia
  • standardized meal

ASJC Scopus subject areas

  • Gastroenterology

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