Hepatic amino-acid metabolism in liver cirrhosis and in the long-term course after liver transplantation

The aim of this study was to investigate the impact of orthotopic liver transplantation (OLT) on plasma levels and splanchnic turnover of key amino acids for muscular (branched-chain amino acids: BCAAs) and hepatic metabolism (aromatic amino acids (AAAs) and methionine) in 48 patients with cirrhosis, 14 patients after OLT, and 46 controls. Also, hepatic amino-acid supply and resting energy expenditure were measured. BCAA levels (no hepatic uptake) decreased in cirrhosis (P < 0.001) and were improved, although not normalized, after OLT (P < 0.001). AAA and methionine levels were raised in cirrhosis (P < 0.001) and normalized after OLT (P < 0.001). Hepatic supply of these amino acids increased in patients graded Child B and C and decreased significantly after OLT. Splanchnic uptake of AAAs and methionine increased significantly in Child-B and decreased in Child-C patients. After OLT, splanchnic extraction of AAAs and methionine was as in Child A. Circulating AAAs and methionine correlated with indocyanine-green half-life (r = 0.71, P < 0.001) and resting energy expenditure (r = 0.50, P < 0.001), indicating that levels of circulating AAAs and methionine in cirrhosis are determined by hepatic and extrahepatic metabolic factors. This study demonstrates persistent changes in muscular metabolism of BCAAs after OLT, while the hepatic amino-acid metabolism is normalized due to (1) a significant reduction in the rate of peripheral proteolysis, and (2) improved liver function compared with that in patients with cirrhosis.