Abstract

Low plasma levels of branched chain amino acids (BCAA) in liver cirrhosis are associated with hepatic encephalopathy (HE). We aimed to identify a metabolic signature of minimal hepatic encephalopathy (MHE) in malnourished cirrhotic patients and evaluate its modification with oral nutritional supplements (ONS) enriched with ß-Hydroxy-ß-methylbutyrate (HMB), a derivative of the BCAA leucine. Post hoc analysis was conducted on a double-blind placebo-controlled trial of 43 individuals with cirrhosis and malnutrition, who were randomized to receive, for 12 weeks, oral supplementation twice a day with either 220 mL of Ensure® Plus Advance (HMB group, n = 22) or with 220 mL of Ensure® Plus High Protein (HP group, n = 21). MHE evaluation was by psychometric hepatic encephalopathy score (PHES). Compared to the HP group, an HMB-specific treatment effect led to a larger increase in Val, Leu, Phe, Trp and BCAA fasting plasma levels. Both treatments increased Fischer’s ratio and urea without an increase in Gln or ammonia fasting plasma levels. MHE was associated with a reduced total plasma amino acid concentration, a reduced BCAA and Fischer´s ratio, and an increased Gln/Glu ratio. HMB-enriched ONS increased Fischer´s ratio without varying Gln or ammonia plasma levels in liver cirrhosis and malnutrition, a protective amino acid profile that can help prevent MHE.

Highlights

  • Malnutrition in cirrhosis is characterized by an increase in fatty acid oxidation, reduced utilization of glucose as energy source, and decreased protein synthesis

  • Gluconeogenesis is increased in early stages of liver cirrhosis and the skeletal muscle is the main source of amino acids by proteolysis

  • We sought to investigate the difference in plasma amino acid profile between cirrhotic patients with clinical malnutrition (n = 43) and healthy individuals (n = 31) matched for age and sex

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Summary

Introduction

Malnutrition in cirrhosis is characterized by an increase in fatty acid oxidation, reduced utilization of glucose as energy source, and decreased protein synthesis. All these processes converge into a loss of muscle mass [1]. Gluconeogenesis is increased in early stages of liver cirrhosis and the skeletal muscle is the main source of amino acids by proteolysis. As a result, both aromatic (AAA) and branched chain amino acids (BCAA) are generated [2]. BCAA are catabolized in the skeletal muscle and AAA are primarily metabolized in the liver. Plasma BCAA concentrations and Fischer s ratio (BCAA/AAA)

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