Abnormalities in branched-chain amino acid metabolism in cirrhosis: influence of hormonal and nutritional factors and directions for future research

Plasma branched-chain amino acid (BCAA) levels are decreased in patients wi th liver cirrhosis, owing to an increase in BCAA tissue uptake and/or catab olism and a decrease in BCAA production from proteins. Non-specific factors such as malnutrition worsen this picture. Studies of BCAA fluxes and prote in turnover in cirrhotic patients have given conflicting results due to pat ient heterogeneity, differences in method and bias in the expression of res ults. In well compensated cirrhosis, muscle wasting is moderate and probabl y due more to decreased protein synthesis than to increased protein catabol ism. Hyperinsulinemia has been suggested as the main cause of decreased BCAA lev els, by increasing BCAA uptake in muscle and additionally in adipose tissue . However, as depletion of fat stores is frequent in cirrhosis, this effect is certainly quantitatively weak. Also, there is no correlation between st ate of hyperinsulinemia and decrease in BCAA levels. An effect of cytokines (IL1 and TNF) on muscle BCAA catabolism is a possibility. Until recently, the contribution of the liver to abnormal BCAA metabolism h as been underestimated. In cirrhotic liver an increase in liver transaminat ion of branched-chain keto acids (BCKAs) has been suggested and may result from inhibition of liver BCKA dehydrogenase. A modification of protein turn over in cirrhotic liver must be also considered. Lastly, the contribution o f non-hepatocyte liver cells, which are activated in cirrhosis, remains to be assessed.