title: Oral l-ornithine-l-aspartate in minimal hepatic encephalopathy: A randomized, double-blind, placebo-controlled trial.
abstract: OBJECTIVE
  Evaluate efficacy/safety of oral l-ornithine-l-aspartate (LOLA) in controlling minimal hepatic encephalopathy (MHE).
  
  
  METHODS
  Consecutive cirrhotic outpatients with MHE (defined by psychometric number connection tests A/B [NCT-A/B] and digit symbol substitution test [DSST] score of >2 standard deviations) were randomized to a 60-day oral LOLA (5 g t.i.d) or placebo group. Critical flicker frequency test (CFF), quantitative electroencephalogram (qEEG), arterial ammonia (NH3), Beck's anxiety-depression forms and liver disease quality of life (LD-QOL) were assessed. Patients were followed for 6 months after the end of the study to assess LOLA prophylactic role on overt hepatic encephalopathy (OHE).
  
  
  RESULTS
  Sixty-four patients were included, 63 (98.4%) with MHE. In six of these patients, CFT was less than 39 Hz (9.52%); NH3 was increased in 32 (50.8%); 25% had abnormal qEEG. Age, sex, scholarship, Child-Pugh (CP), Model for End-Stage Liver Disease, NCT-A/B, DSST, CFF and NH3 were similar in both groups at the baseline. LOLA led to a significant improvement in NCT-B age-controlled z-score (3.4 ± 3.4 vs 1.5 ± 2.3, P = 0.01) and CFF (42.2 ± 5.8 vs 45.2 ± 5.8, P = 0.02), comparing the first and the last visit, but there were no differences between LOLA and placebo regarding the whole psychometric battery, CFF, LD-QOL and Beck's forms. No serious adverse effects occurred. Patients taking LOLA had less episodes of OHE at 6 months (5% vs 37.9%, P = 0.016), as they have significant improvement on liver function assessed by CP (P < 0.001).
  
  
  CONCLUSIONS
  A 60-day oral LOLA course was not better than placebo in treating MHE, but was useful in preventing further episodes of OHE.
authors.affiliation: School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Division of Gastroenterology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
authors.forename: Mario Reis
authors.initials: MR
authors.lastname: Alvares-da-Silva
authors.forename: Alexandre
authors.initials: A
authors.lastname: de Araujo
authors.forename: João Reinhardt
authors.initials: JR
authors.lastname: Vicenzi
authors.forename: Gabriel Veber
authors.initials: GV
authors.lastname: da Silva
authors.forename: Fabiana Bazanella
authors.initials: FB
authors.lastname: Oliveira
authors.forename: Fernando
authors.initials: F
authors.lastname: Schacher
authors.forename: Lucas
authors.initials: L
authors.lastname: Oliboni
authors.forename: Aline
authors.initials: A
authors.lastname: Magnus
authors.forename: Leticia Pinto
authors.initials: LP
authors.lastname: Kruel
authors.forename: Rita
authors.initials: R
authors.lastname: Prieb
authors.forename: Luiz Nelson Teixeira
authors.initials: LN
authors.lastname: Fernandes
keywords: cirrhosis; flicker test; l-ornithine-l-aspartate; minimal hepatic encephalopathy; psychometric test