Impaired metabolism of methionine in severe liver diseases. I. Clinical and pathophysiological significance of elevated serum methionine levels.

Serum methionine levels increased to a greater extent in patients with severe liver diseases such as fulminant hepatitis and liver cirrhosis with and without hepatic encephalopathy. However, the concentrations remained unchanged in non-encephalopathic cirrhotic cases associated with hepatocellular carcinoma, and their serum methionine levels increased only moderately even at the time of encephalopathy. At least two different mechanisms of serum methionine elevations, possibly due to release from injured hepatocytes or diminished catabolisms of this amino acid in the damaged liver, could be differentiated; the former would be involved mainly in fulminant hepatitis and the latter in liver cirrhosis. A methionine-loading test performed in cirrhotic patients supported the validity of these considerations. No significant increase of serum methionine levels in cirrhotic patients with hepatocellular carcinoma was observed, possibly by remarkable consumption of this amino acid in hepatoma tissues. During the clinical course of several patients, serial determinations of serum methionine concentrations indicated that the levels varied depending upon alterations in the pathophysiological state of the damaged liver; much higher levels were observed concomitantly with decompensated signs such as ascites, jaundice and hepatic encephalopathy. These results suggest that monitoring of serum methionine levels would be very valuable, especially for judging prognosis and predicting hepatic encephalopathy in severe liver disease.