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Hepatic encephalopathy

Nature Reviews Disease Primers volume 8, Article number: 43 (2022) Cite this article

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Abstract

Hepatic encephalopathy (HE) is a prognostically relevant neuropsychiatric syndrome that occurs in the course of acute or chronic liver disease. Besides ascites and variceal bleeding, it is the most serious complication of decompensated liver cirrhosis. Ammonia and inflammation are major triggers for the appearance of HE, which in patients with liver cirrhosis involves pathophysiologically low-grade cerebral oedema with oxidative/nitrosative stress, inflammation and disturbances of oscillatory networks in the brain. Severity classification and diagnostic approaches regarding mild forms of HE are still a matter of debate. Current medical treatment predominantly involves lactulose and rifaximin following rigorous treatment of so-called known HE precipitating factors. New treatments based on an improved pathophysiological understanding are emerging.

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Fig. 1: Model for the pathogenesis of HE.
Fig. 2: Mechanisms and consequences of oxidative/nitrosative stress in astrocytes in HE.
Fig. 3: Glutamine formation triggers oxidative stress in astrocytes through protein O-GlcNAcylation.
Fig. 4: Steps involved in the process by which liver damage leads to cognitive and motor impairment in MHE and HE.
Fig. 5: Classification of severity of HE.
Fig. 6: Algorithms for assessment of HE and treatment in stable outpatients and hospitalized patients with cirrhosis.

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Authors and Affiliations

  1. Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany

    Dieter Häussinger & Boris Görg

  2. Department of Hepatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, (Uttar Pradesh), India

    Radha K. Dhiman

  3. Laboratory of Neurobiology, Centro de Investigación Principe Felipe, Valencia, Spain

    Vicente Felipo

  4. Liver Failure Group ILDH, Division of Medicine, UCL Medical School, Royal Free Campus, London, UK

    Rajiv Jalan

  5. European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain

    Rajiv Jalan

  6. Department of Gastroenterology, Diabetology and Hepatology, University Hospital Brandenburg an der Havel, Brandenburg Medical School, Brandenburg an der Havel, Germany

    Gerald Kircheis

  7. Department of Translational and Precision Medicine, Universita’ degli Studi di Roma – Sapienza, Roma, Italy

    Manuela Merli

  8. Department of Medicine, University of Padova, Padova, Italy

    Sara Montagnese

  9. UCM Digestive Diseases, Virgen del Rocío University Hospital, Institute of Biomedicine of Seville (HUVR/CSIC/US), University of Seville, Seville, Spain

    Manuel Romero-Gomez

  10. Institute of Clinical Neuroscience and Medical Psychology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany

    Alfons Schnitzler

  11. Department of Surgery and Cancer, St. Mary’s Hospital Campus, Imperial College London, London, UK

    Simon D. Taylor-Robinson

  12. Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark

    Hendrik Vilstrup

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Contributions

Introduction (D.H.); Epidemiology (D.H. and H.V.); Mechanisms/pathophysiology (D.H., B.G., V.F. and A.S.); Diagnosis, screening and prevention (D.H., S.M., G.K., S.D.T.-R. and M.R.-G.); Management (D.H., H.V., S.M., M.M. and R.J.); Quality of life (D.H., H.V., G.K. and R.K.D.); Outlook (D.H. and R.J.); Overview of Primer (D.H.).

Corresponding author

Correspondence to Dieter Häussinger.

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Competing interests

D.H. and G.K. are members of the “Flicker Diagnostics GbR”. The S.M. group has received research funding from AlfaSigma S.p.a., Norgine Ltd., Merz Pharmaceuticals GmbH, Umecrine Cognition AB and Versantis AG. R.J. has research collaborations with Yaqrit Ltd. and Takeda. R.J. is the inventor of OPA, which has been patented by University College London and licensed to Mallinckrodt Pharma. He is also the founder of Yaqrit Ltd., a spin-out company from University College London, Cyberliver Ltd. and Hepyx Ltd. S.D.T.-R., B.G., M.R.-G., M.M., R.K.D., H.V., A.S. and V.F. declare no competing interests.

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Nature Reviews Disease Primers thanks Patrick Kamath, Naveen Nasser-Ghodsi and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Häussinger, D., Dhiman, R.K., Felipo, V. et al. Hepatic encephalopathy. Nat Rev Dis Primers 8, 43 (2022). https://doi.org/10.1038/s41572-022-00366-6

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