Effects of long-term oral misoprostol administration on hepatic amino acid–nitrogen metabolism in patients with cirrhosis

Background: The acute infusion of a Prostaglandin of E series 1 (PGE1) analogue results in nitrogen sparing in cirrhosis. Aims: To test the effects of long-term oral PGE1 on hepatic and whole-body nitrogen metabolism. Patients and methods: Ten patients with advanced cirrhosis were studied in paired experiments, before and 30–50 days after oral misoprostol therapy. α-Amino-nitrogen levels and urea-nitrogen synthesis rate were measured in the post-absorptive state and in response to continuous alanine infusion (2 mmol/kg per hour for 4.5 h). Data were used to compute the functional hepatic nitrogen clearance, i.e. the slope of the regression of α-amino-N levels to urea-N synthesis rate, and the apparent nitrogen exchange. Results: Misoprostol reduced urea-N synthesis rate (during fasting and in response to alanine), resulting in a positive nitrogen exchange. The functional hepatic nitrogen clearance slightly increased, and the regression line was rightwards shifted, indicating a reduced urea synthesis rate at any α-amino-N concentration. Amino acid- and ammonia-N did not accumulate in plasma. No systematic effects on insulin and glucagon were observed. Conclusions: Data are consistent with a nitrogen sparing mechanism of misoprostol, not mediated by hormone levels. These effects may be beneficial in clinical hepatology, and need to be tested in controlled trials.