Secondary prophylaxis of hepatic encephalopathy in cirrhosis of liver: a double-blind randomized controlled trial of L-ornithine L-aspartate versus placebo.

Abstract

BACKGROUND AND AIMS:

Hepatic encephalopathy (HE) is associated with a poor prognosis. There is no study on the prevention of recurrence of encephalopathy with L-ornithine L-aspartate (LOLA).

PATIENTS AND METHODS:

We conducted a double-blind randomized controlled trial at a tertiary center. Consecutive patients with cirrhosis who had recovered from HE were randomized to receive LOLA (6 g thrice daily) or similar amount of placebo by computer-based randomization for 6 months. Patients were assessed by psychometric HE scores using five paper-pencil tests, critical flicker frequency test, arterial ammonia, and sickness impact profile scores at inclusion. Primary end point was development of overt HE.

RESULTS:

Of 306 patients, 150 patients were enrolled. HE recurred in nine (12.3%) of 73 and in 20 (27.7%) of 72 patients receiving LOLA and placebo, respectively (P=0.02), with hazard ratio of 0.389 (95% confidence interval=0.174-0.870). Mortality was similar in both groups (6.8 vs. 13.8%, P=0.18). At 6 months follow-up, there was a significant change in the psychometric hepatic encephalopathy score (2.53±2.18 vs. -0.01±1.92, P<0.001), ammonia level (-23.58±14.8 vs. 1.41±13.34 μmol/l, P<0.001), CFF (5.85±4.82 vs. 0.58±4.53, P<0.001), and SIP scores (-7.89±5.52 vs. -0.95±4.25, P<0.001) in patients treated with LOLA compared with placebo. On multivariate analysis, only MELD score predicted the recurrence of overt HE, with odds ratio of 2.21 (95% confidence interval: 1.526-3.204, P<0.001).

CONCLUSION:

LOLA is effective in the secondary prophylaxis of HE and is associated with significant improvements in psychometric hepatic encephalopathy score, ammonia level, critical flicker frequency scores, and health-related quality of life.

• Authors: Shivakumar Varakanahalli, Barjesh C Sharma, Siddharth Srivastava, Sanjeev Sachdeva, Amol S Dahale
• Journal: European journal of gastroenterology & hepatology (Eur J Gastroenterol Hepatol) Vol. 30 Issue 8 Pg. 951-958 (08 2018) ISSN: 1473-5687 [Electronic] England
• PMID: 29727385 (Publication Type: Journal Article, Randomized Controlled Trial)

Chemical References

• Biomarkers
• Dipeptides
• Ammonia
• ornithylaspartate

Topics

• Adult
• Ammonia (blood)
• Biomarkers (blood)
• Chi-Square Distribution
• Dipeptides (administration & dosage, adverse effects)
• Double-Blind Method
• Female
• Flicker Fusion
• Hepatic Encephalopathy (blood, diagnosis, mortality, prevention & control)
• Humans
• India
• Kaplan-Meier Estimate
• Liver Cirrhosis (blood, diagnosis, drug therapy, mortality)
• Logistic Models
• Male
• Middle Aged
• Multivariate Analysis
• Neuropsychological Tests
• Odds Ratio
• Psychometrics
• Recurrence
• Risk Factors
• Secondary Prevention (methods)
• Sickness Impact Profile
• Tertiary Care Centers
• Time Factors
• Treatment Outcome