Evidence map›Paper›PMID 30201461›Full record

ArticleJournal of hepatology2019

Impaired brain glymphatic flow in experimental hepatic encephalopathy.

Anna Hadjihambi, Ian F Harrison, Marta Costas-Rodríguez, Frank Vanhaecke, Natalia Arias, Rocío Gallego-Durán, Svetlana Mastitskaya, Patrick S Hosford, Steven W M Olde Damink, Nathan Davies and 4 more

Erratum issuedOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of hepatology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
3.5field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

59 citing papers in PubMed, 99 citations in OpenAlex.

  1. The role of ammonia in chronic liver disease.Hepatology communications · 2026
    Review
  2. Article
  3. Review
  4. Article
  5. Mechanistic insights into the liver-brain axis during chronic liver disease.Nature reviews. Gastroenterology & hepatology · 2026
    Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Hepatic Encephalopathy: Current Thoughts on Pathophysiology and Management.Current neurology and neuroscience reports · 2025
    Review
  16. Review
  17. Article
  18. Review
  19. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 5 institutions in 4 countries.

Anna HadjihambiLiver Failure Group Institute for Liver and Digestive Health, Division of Medicine, UCL Medical School, Royal Free Hospital, Rowland Hill Street, NW3 2PF London, UK; Centre for Cardiovascular and Metabolic Neuroscience, Neuroscience, Physiology and Pharmacology, University College London, WC1E 6BT London, UK.
Ian F HarrisonUCL Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, WC1E 6BT London, UK.
Marta Costas-RodríguezGhent University, Department of Chemistry, Atomic and Mass Spectrometry - A&MS Research Unit, Campus Sterre, Krijgslaan 281-S12, BE-9000 Ghent, Belgium.
Frank VanhaeckeGhent University, Department of Chemistry, Atomic and Mass Spectrometry - A&MS Research Unit, Campus Sterre, Krijgslaan 281-S12, BE-9000 Ghent, Belgium.
Natalia AriasLiver Failure Group Institute for Liver and Digestive Health, Division of Medicine, UCL Medical School, Royal Free Hospital, Rowland Hill Street, NW3 2PF London, UK.
Rocío Gallego-DuránInstitute of Biomedicine of Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, UCM Digestive Diseases & CIBERehd Sevilla, Spain.
Svetlana MastitskayaCentre for Cardiovascular and Metabolic Neuroscience, Neuroscience, Physiology and Pharmacology, University College London, WC1E 6BT London, UK.
Patrick S HosfordCentre for Cardiovascular and Metabolic Neuroscience, Neuroscience, Physiology and Pharmacology, University College London, WC1E 6BT London, UK.
Steven W M Olde DaminkDepartment of Surgery, Maastricht University, Maastricht, the Netherlands.
Nathan DaviesLiver Failure Group Institute for Liver and Digestive Health, Division of Medicine, UCL Medical School, Royal Free Hospital, Rowland Hill Street, NW3 2PF London, UK.
Abeba HabtesionLiver Failure Group Institute for Liver and Digestive Health, Division of Medicine, UCL Medical School, Royal Free Hospital, Rowland Hill Street, NW3 2PF London, UK.
Mark F LythgoeUCL Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, WC1E 6BT London, UK.
Alexander V GourineCentre for Cardiovascular and Metabolic Neuroscience, Neuroscience, Physiology and Pharmacology, University College London, WC1E 6BT London, UK.
Rajiv JalanLiver Failure Group Institute for Liver and Digestive Health, Division of Medicine, UCL Medical School, Royal Free Hospital, Rowland Hill Street, NW3 2PF London, UK. Electronic address: r.jalan@ucl.ac.uk.
The Royal Free Hospital · GBUniversity College London · GBGhent University · BEHospital Universitario Virgen del Rocío · ESMaastricht University · NL

Funding

Medical Research Council MR/K026739/1Wellcome Trust 095064Wellcome Trust 200893Wellcome Trust 200893/Z/16/Z
6 · The paper itself

Abstract

BACKGROUND &

aimsNeuronal function is exquisitely sensitive to alterations in the extracellular environment. In patients with hepatic encephalopathy (HE), accumulation of metabolic waste products and noxious substances in the interstitial fluid of the brain is thought to result from liver disease and may contribute to neuronal dysfunction and cognitive impairment. This study was designed to test the hypothesis that the accumulation of these substances, such as bile acids, may result from reduced clearance from the brain.

methodsIn a rat model of chronic liver disease with minimal HE (the bile duct ligation [BDL] model), we used emerging dynamic contrast-enhanced MRI and mass-spectroscopy techniques to assess the efficacy of the glymphatic system, which facilitates clearance of solutes from the brain. Immunofluorescence of aquaporin-4 (AQP4) and behavioural experiments were also performed.

resultsWe identified discrete brain regions (olfactory bulb, prefrontal cortex and hippocampus) of altered glymphatic clearance in BDL rats, which aligned with cognitive/behavioural deficits. Reduced AQP4 expression was observed in the olfactory bulb and prefrontal cortex in HE, which could contribute to the pathophysiological mechanisms underlying the impairment in glymphatic function in BDL rats.

conclusionsThis study provides the first experimental evidence of impaired glymphatic flow in HE, potentially mediated by decreased AQP4 expression in the affected regions. LAY SUMMARY: The 'glymphatic system' is a newly discovered brain-wide pathway that facilitates clearance of various substances that accumulate in the brain due to its activity. This study evaluated whether the function of this system is altered in a model of brain dysfunction that occurs in cirrhosis. For the first time, we identified that the clearance of substances from the brain in cirrhosis is reduced because this clearance system is defective. This study proposes a new mechanism of brain dysfunction in patients with cirrhosis and provides new targets for therapy.

Indexed as

AnimalsAquaporin 4BrainCerebrospinal FluidDisease Models, AnimalGlymphatic SystemHepatic EncephalopathyIntracranial PressureMagnetic Resonance ImagingMaleRatsRats, Sprague-DawleyAqp4 protein, ratAquaporin 4CirrhosisGlymphatic systemHepatic encephalopathyMass spectrometryMRI

Identifiers

PMID30201461
PMCPMC7613052
OpenAlexW2892352916

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.