Systematic ReviewEfficacy of l-Ornithine l-Aspartate for the Treatment of Hepatic Encephalopathy and Hyperammonemia in Cirrhosis: Systematic Review and Meta-Analysis of Randomized Controlled Trials
Section snippets
Search Criteria
This involved electronic and manual searches using appropriate keywords as follows: Search strings: (1) Hepatic Encephalopathy (HE), (2) Overt Hepatic Encephalopathy (OHE), (3) Minimal Hepatic Encephalopathy (MHE), (4) l-Ornithine l-Aspartate (LOLA), (5) Intravenous Formulation (iv), (6) oral formulation (oral), (7) cirrhosis, (8) Randomized Controlled Trial (RCT). Search string: (#1 or #2 or #3) and (#4 or #5) and #7 and #8. Medline, PubMed, the Cochrane Controlled Trials Register (2008),
Results
Electronic searches of the databases identified 43 trials with a further 16 from manual searches. Five full-text articles were excluded for reasons of incompatibility of data presentation required for pooling. Following removal of duplicate citations and elimination of published studies in line with eligibility and inclusion/exclusion criteria, a total of 10 trials were included in the final meta-analysis (Figure 1) where sufficient data were available for pooling. Included trials are
Discussion
Hyperammonemia: Results of the present systematic review and meta-analysis significantly extend the findings of a number of individual RCTs namely that LOLA is effective in lowering blood ammonia in patients with cirrhosis. Pooled data from the eight RCTs in which blood ammonia was measured in all patients with HE revealed that blood ammonia was significantly reduced although the degree of reduction was variable from trial-to-trial, the overall effect was statistically significant (MD: −17.50,
Conflicts of Interest
The authors have none to declare.
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Cited by (47)
Efficacy of L-ornithine L-aspartate for minimal hepatic encephalopathy in patients with cirrhosis: A meta-analysis of randomized controlled trials
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2022, Developmental and Comparative ImmunologyCitation Excerpt :It has been shown to reduce blood ammonia levels in mammal experiment with hyperammonemia (Rose et al., 1999). Several mechanisms have been proposed to explain the effect of LoLa on hyperammonemia: 1) participates in ammonia metabolism via l-ornithine and/or l-aspartate and related metabolites including glutamate, glutamine and glutathione; 2) increases nitric oxide synthesis by increasing arginine production; 3) increases glutathione synthesis from glutamate and reduces harmful reactive species contents, thereby enhancing antioxidant capacity; 4) reduces the occurrence of hepatocyte necrosis and apoptosis (Butterworth and Gruengreiff, 2018; Butterworth et al., 2018; Sidhu, 2018). In aquaculture, LoLa has potential value in treating ammonia poisoning in fish due to its low price.
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2021, Clinical Nutrition ESPENCitation Excerpt :Therefore, LOLA enhances ammonia clearance through these dual pathways [71]. In clinical trials, LOLA improves both overt and minimal hepatic encephalopathy [72]. Furthermore, the metabolites of LOLA including glutamine, l-arginine and glutathione have potent antioxidant properties and improve hepatic microcirculation which may have additional hepatoprotective effects [73].
Hepatic encephalopathy: Novel insights into classification, pathophysiology and therapy
2020, Journal of HepatologyCitation Excerpt :The efficacy of oral LOLA has been a subject of debate, as the AASLD-EASL clinical guidelines suggested that oral supplementation with LOLA is not effective.1 Recent meta-analyses204–206 suggest that LOLA has beneficial effects on HE, decompensation, and mortality, but the number of clinical trials analysed was dissimilar in the reports, with one stating that the quality of evidence was very low.206 Thus, the potential beneficial effect of LOLA remain uncertain.
The assessment and management of cirrhotic patients with encephalopathy
2024, United European Gastroenterology JournalFrailty in end-stage liver disease: Understanding pathophysiology, tools for assessment, and strategies for management
2023, World Journal of Gastroenterology