Background.The amino acid (AA) metabolism in cirrhosis is deranged, reflected by an altered plasma AA profile. Alanine is a unique AA with predominant production by muscle and the highest hepatic extraction rate.Methods.We studied circulating levels and hepatic alanine extraction in 52 patients with advanced cirrhosis, 16 stable patients more than 6 months after orthotopic liver transplant (OLT), and 50 controls. In addition, hepatic hemodynamics (portal pressure, hepatic blood flow, and splanchnic percent indocyanine green extraction) and parameters of hepatic metabolism (splanchnic oxygen uptake and splanchnic glucose production) were assessed.Results.Circulating alanine levels decreased independently of the clinical stage in cirrhosis (262±15 &mgr;mol/L vs. 330±14 &mgr;mol/L in controls,P<0.001) and decreased even further after OLT (209±10 &mgr;mol/L,P<0.001). Hepatic alanine extraction decreased dependently on the clinical stage in cirrhosis (59±7 &mgr;mol/min) and was normalized after OLT (100±10 &mgr;mol/min,P<0.001), indicating that decreased plasma alanine levels in OLT patients are the result of changes in extrahepatic metabolism. Hepatic alanine extraction correlated with splanchnic oxygen uptake (r=0.64,P<0.001) and hepatic glucose production (r=0.65,P<0.001).Conclusions.These results demonstrate that significant alterations in muscular AA metabolism persist even in the clinically stable long-term course after OLT when the hepatic AA metabolism is normalized.