ORAL L-ORNITHINE-L-ASPARTATE THERAPY OF CHRONIC HEPATIC-ENCEPHALOPATHY - RESULTS OF A PLACEBO-CONTROLLED DOUBLE-BLIND-STUDY

Background/Aims: In the current state of knowledge of the pathophysiol ogy of hepatic encephalopathy, a reduction in hyperammonemia is the mo st important evidence of effective treatment, Therefore, the therapeut ic efficacy of oral L-ornithine-L-aspartate, which improves impaired a mmonia detoxification, was investigated in patients with cirrhosis, hy perammonemia and stable, overt, chronic hepatic encephalopathy, and in subclinical hepatic encephalopathy in a randomized, double-blind, pla cebo-controlled clinical trial. Methods: Oral L-ornithine-L-aspartate was administered three times daily at fixed times for 14 consecutive d ays in a total dose of 18 g per day, The design was chosen to prevent an increase in ammonia induced by a protein meal of 0.25 g/kg body wei ght, given at the start of the daily treatment period, Efficacy variab les were: fasting and postprandial ammonia concentration, Number-Conne ction-Test time, mental state grades, and a Portosystemic Encephalopat hy Index, Analyses were based on the total study sample of 32 placebo- and 34 L-ornithine-L-aspartate-treated patients as well as on the subg roup samples in the overt (20 placebo- and 23 L-ornithine-L-aspartate- treated) and subclinical hepatic encephalopathy (12 placebo-and 11 L-o rnithine-L-aspartate-treated) patients. Results: Number Connection Tes t performance times (p<0.01) as well as fasting (p<0.01) and postprand ial (p<0.05) venous blood ammonia concentrations in the L-ornithine-L- aspartate-treated group showed improvement in comparison to placebo. A lso, the mental state grade (p<0.05) and the Portosystemic Encephalopa thy Index (p<0.01), improved to a much greater degree in the L-ornithi ne-L-aspartate group than in the placebo group, Adverse events were ob served in neither the placebo nor the L-ornithine-L-aspartate-treated patients. Conclusion: Oral L-ornithine-L-aspartate is a safe, well-tol erated treatment with a good compliance rate and a beneficial therapeu tic effect in patients with cirrhosis and stable, overt, chronic hepat ic encephalopathy.