Oral l-ornithine-l-aspartate in minimal hepatic encephalopathy: A randomized, double-blind, placebo-controlled trial

Aim: 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).

Conclusion: A 60-day oral LOLA course was not better than placebo in treating MHE, but was useful in preventing further episodes of OHE.