title: Oral L-ornithine-L-aspartate therapy of chronic hepatic encephalopathy: results of a placebo-controlled double-blind study.
abstract: OBJECTIVE
  In the current state of knowledge of the pathophysiology of hepatic encephalopathy, a reduction in hyperammonemia is the most important evidence of effective treatment. Therefore, the therapeutic efficacy of oral L-ornithine-L-aspartate, which improves impaired ammonia detoxification, was investigated in patients with cirrhosis, hyperammonemia and stable, overt, chronic hepatic encephalopathy, and in subclinical hepatic encephalopathy in a randomized, double-blind, placebo-controlled clinical trial.
  
  
  METHODS
  Oral L-ornithine-L-aspartate was administered three times daily at fixed times for 14 consecutive days 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 weight, given at the start of the daily treatment period. Efficacy variables were: fasting and postprandial ammonia concentration, Number-Connection-Test time, mental state grades, and a Portosystemic Encephalopathy 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 subgroup samples in the overt (20 placebo- and 23 L-ornithine-L-aspartate-treated) and subclinical hepatic encephalopathy (12 placebo- and 11 L-ornithine-L-aspartate-treated) patients.
  
  
  RESULTS
  Number Connection Test performance times (p<0.01) as well as fasting (p<0.01) and postprandial (p<0.05) venous blood ammonia concentrations in the L-ornithine-L-aspartate-treated group showed improvement in comparison to placebo. Also, the mental state grade (p<0.05) and the Portosystemic Encephalopathy Index (p<0.01), improved to a much greater degree in the L-ornithine-L-aspartate group than in the placebo group. Adverse events were observed in neither the placebo nor the L-ornithine-L-aspartate-treated patients.
  
  
  CONCLUSIONS
  Oral L-ornithine-L-aspartate is a safe, well-tolerated treatment with a good compliance rate and a beneficial therapeutic effect in patients with cirrhosis and stable, overt, chronic hepatic encephalopathy.
authors.affiliation: Hospital Nordwest, Dept. of Internal Medicine, Frankfurt/Main, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Stauch
authors.forename: G
authors.initials: G
authors.lastname: Kircheis
authors.forename: G
authors.initials: G
authors.lastname: Adler
authors.forename: K
authors.initials: K
authors.lastname: Beckh
authors.forename: H
authors.initials: H
authors.lastname: Ditschuneit
authors.forename: R
authors.initials: R
authors.lastname: Görtelmeyer
authors.forename: R
authors.initials: R
authors.lastname: Hendricks
authors.forename: A
authors.initials: A
authors.lastname: Heuser
authors.forename: C
authors.initials: C
authors.lastname: Karoff
authors.forename: P
authors.initials: P
authors.lastname: Malfertheiner
authors.forename: D
authors.initials: D
authors.lastname: Mayer
authors.forename: W
authors.initials: W
authors.lastname: Rösch
authors.forename: J
authors.initials: J
authors.lastname: Steffens
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000641:Ammonia / Q000097:blood*; D004044:Dietary Proteins; D004151:Dipeptides / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006501:Hepatic Encephalopathy / Q000097:blood / Q000188:drug therapy* / Q000523:psychology; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D009483:Neuropsychological Tests; D010919:Placebos; D019518:Postprandial Period
chemical_list: D004044:Dietary Proteins; D004151:Dipeptides; D010919:Placebos; D000641:Ammonia; C002939:ornithylaspartate