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Mechanisms, diagnosis and management of hepatic encephalopathy

Nature Reviews Gastroenterology & Hepatology volume 7, pages 515–525 (2010)Cite this article

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Abstract

Hepatic encephalopathy (HE) is a serious neuropsychiatric complication of both acute and chronic liver disease. Symptoms of HE can include confusion, disorientation and poor coordination. A general consensus exists that the synergistic effects of excess ammonia and inflammation cause astrocyte swelling and cerebral edema; however, the precise molecular mechanisms that lead to these morphological changes in the brain are unclear. Cerebral edema occurs to some degree in all patients with HE, regardless of its grade, and could underlie the pathogenesis of this disorder. The different grades of HE can be diagnosed by a number of investigations, including neuropsychometric tests (such as the psychometric hepatic encephalopathy score), brain imaging and clinical scales (such as the West Haven criteria). HE is best managed by excluding other possible causes of encephalopathy alongside identifying and the precipitating cause, and confirming the diagnosis by a positive response to empiric treatment. Empiric therapy for HE is largely based on the principle of reducing the production and absorption of ammonia in the gut through administration of pharmacological agents such as rifaximin and lactulose, which are approved by the FDA for the treatment of HE.

Key Points

  • Hepatic encephalopathy (HE) is a serious neuropsychiatric complication of acute and chronic liver disease

  • Inflammation and raised levels of ammonia in the blood (owing to diminished clearance of ammonia by the liver) underlie the pathogenesis of HE

  • Some degree of cerebral edema is observed in all grades of HE

  • The occurrence of any neuropsychiatric manifestation in patients with liver disease should be treated as HE unless proven otherwise

  • An acute episode of HE is managed by a tripartite strategy: ruling out other causes of encephalopathy, identifying the precipitating cause and initiating empiric therapy

  • Rifaximin and lactulose are the only two medications approved by FDA for long-term treatment of HE

  • Work-up for liver transplantation must be initiated as early as possible

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Figure 1: Classification of hepatic encephalopathy (HE) proposed by the Working Party at the 1998 World Congress of Gastroenterology, Vienna, Austria.
Figure 2: Management of patients with hepatic encephalopathy (HE).

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Acknowledgements

Désirée Lie, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the MedscapeCME-accredited continuing medical education activity associated with this article.

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  1. Division of Gastroenterology, MetroHealth Medical Center, Case Western Reserve University, 2500 MetroHealth Drive, Cleveland, 44109, OH, USA

    Ravi Prakash & Kevin D. Mullen

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R. Prakash and K. D. Mullen contributed equally to researching data for the article, to substantial discussion of the content, to writing the article, and to reviewing and/or editing the manuscript before submission.

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K. D. Mullen is a consultant for Ocera Therapeutics and a consultant and speaker for Salix Pharmaceuticals (he has received honoria, but not for this manuscript). R. Prakash declares no competing interests.

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Prakash, R., Mullen, K. Mechanisms, diagnosis and management of hepatic encephalopathy. Nat Rev Gastroenterol Hepatol 7, 515–525 (2010). https://doi.org/10.1038/nrgastro.2010.116

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