P30 L-Ornithine L-Aspartate [LOLA] Improves Both Severe Encephalopathy and Survival in Patients With Liver Cirrhosis: Results of RCTs, Systematic Reviews and Meta-Analyses
Bibliographic record
Abstract
Liver cirrhosis invariably leads to alterations of mental state [hepatic encephalopathy (HE)] with associated reductions of life expectancy. The goal of the present study was an update of the evidence base in support of LOLA for the treatment of severe (overt) HE in patients with cirrhosis. Literature searches of the results of randomized controlled trials [RTCs] and their associated systematic reviews with meta-analyses published during the 20-year period from 1998-2018 were examined for inclusion in the analyses. Parameters investigated included effects of LOLA versus placebo or no treatment on hyperammonemia measured by standard biochemical procedures in addition to improvements of mental state assessed by West-Haven Criteria; 28-day survival rates were recorded in all cases. Pooled data from 10 RCTs in the first-published meta-analysis revealed significant beneficial effects of LOLA on blood ammonia and mental state in overt HE with decreased mortality in 6 trials [1]. Comparable benefits were reported in a later Cochrane-based meta-analysis of 15 RCTs [2], In a subsequent RCT, continuous infusions of LOLA in addition to lactulose and rifaximin were found to be more effective than lactulose/rifaximin alone for improvements in OHE grade at day 5 [P<0.03] with significant lowering of 28-day mortality [16.4% vs 41.8% for placebo P<0.001] [3]. Beneficial effects of LOLA were accompanied by greater reductions of blood ammonia and cytokines (TNF-alpha and IL-6). Plausible mechanisms proposed include effects of LOLA on hepatic function via synthesis from LOLA of antioxidants (glutathione, glutamine) and improved hepatic microcirculation via the production of nitric oxide. References 1. Butterworth RF, Kircheis G, Hilger N, McPhail MJW. Efficacy of l-Ornithine l-Aspartate for the Treatment of Hepatic Encephalopathy and Hyperammonemia in Cirrhosis: Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Clin Exp Hepatol. 2018;8(3):301-313. 2. Goh ET, Stokes CS, Sidhu SS, Vilstrup H, Gluud LL, Morgan MY. L-ornithine L-aspartate for prevention and treatment of hepatic encephalopathy in people with cirrhosis. Cochrane Database Syst Rev. 2018;5(5):CD012410. 3. Jain A, Sharma BC, Mahajan B, et al. L-ornithine L-aspartate in acute treatment of severe hepatic encephalopathy: A double-blind randomized controlled trial. Hepatology. 2022;75(5):1194-1203.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.012 | 0.024 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.011 | 0.021 |
| Bibliometrics | 0.004 | 0.004 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.003 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".