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Record W3156032412 · doi:10.1007/s40268-021-00345-4

Ammonia Removal by Metabolic Scavengers for the Prevention and Treatment of Hepatic Encephalopathy in Cirrhosis

2021· review· en· W3156032412 on OpenAlexaff
Roger F. Butterworth

Bibliographic record

VenueDrugs in R&D · 2021
Typereview
Languageen
FieldMedicine
TopicLiver Disease and Transplantation
Canadian institutionsUniversité de Montréal
Fundersnot available
KeywordsHyperammonemiaUrea cycleHepatic encephalopathyLactuloseCirrhosisInternal medicineOrnithineChemistryPhenylbutyrateMedicineEndocrinologyBiochemistryPharmacologyArginineAmino acid

Abstract

fetched live from OpenAlex

Effective lowering of circulating ammonia is the mainstay strategy in the prevention and treatment of hepatic encephalopathy in cirrhosis and there is increasing interest in agents with the metabolic potential for the active removal of ammonia by the liver and skeletal muscle by agents including L-ornithine L-aspartate, branched-chain amino acids, as well as the re-purposing of benzoate and phenylacetate currently employed for the control of hyperammonaemia in congenital urea-cycle enzymopathies. Based upon results of multiple systematic reviews with meta-analyses, L-ornithine L-aspartate demonstrably lowers circulating ammonia in patients with cirrhosis with concomitantly improved mental status. Distinct mechanisms responsible include optimisation of hepatic metabolic pathways for ammonia removal as well as direct hepatoprotective effects involving the release of glutathione and of nitric oxide with beneficial effects on hepatic microcirculation. L-ornithine L-aspartate also prevents cirrhosis-related sarcopenia, leading to increased capacity for ammonia removal by skeletal muscle. Branched-chain amino acids continue to be prescribed as nutritional supplements with the potential to result in improvements in liver function. Sodium benzoate, glycerol phenylbutyrate and an analogous compound L-ornithine phenylacetate were also evaluated. Glycerol phenylbutyrate was the only agent with a beneficial effect on both hyperammonaemia and hepatic encephalopathy. None were superior to lactulose for the lowering of blood ammonia.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Other design · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.990
Threshold uncertainty score0.426

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.032
GPT teacher head0.338
Teacher spread0.306 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designOther design
Domainnot available
GenreReview

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".

Quick stats

Citations28
Published2021
Admission routes1
Has abstractyes

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