The activities of urea-cycle enzymes were measured in liver biopsies of patients suffering from chronic-persistent hepatitis (CPH), chronic-active hepatitis (CAH) and liver cirrhosis. Most of the activities of urea-cycle enzymes did not differ in the case of CPH as compared to controls. Chronic-active hepatitis and liver cirrhosis are associated with a significant (p less than 0.05) decrease of enzyme activity as compared to normal persons. Most of the urea-cycle enzymes are significantly decreased in patients with CAH in comparison with CPH. No significant differences can be demonstrated in the case of CAH as compared to patients with complete cirrhosis. In conclusion, progression of chronic liver disease is associated with increasing alterations of enzyme activities catalyzing a liver specific metabolic pathway. The decrease of the activities of the key enzymes of the urea cycle (Carbamylphosphate-Synthetase and Arginino-succinate-Synthetase) is nearly identical both in CAH and liver cirhosis, although CAH may be a reversible disease. Therefore, marked alterations in the metabolic pathway of ammonia detoxification seem to preceed the histological manifestation of irreversible liver damage.

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