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Hepatic encephalopathy

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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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.).

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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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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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