Hepatic encephalopathy

Last updated: September 11, 2023

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Summarytoggle arrow icon

Hepatic encephalopathy refers to brain dysfunction in the presence of underlying liver disease. It is common in patients with cirrhosis. Precipitating factors include infections, gastrointestinal bleeding, and constipation. Pathophysiology is complex and not completely understood, however, the accumulation of ammonia in the blood plays a central role. Clinical features vary and may include confusion, asterixis, and even coma. Diagnosis of overt hepatic encephalopathy is based on the presence of characteristic clinical features but the diagnosis of covert hepatic encephalopathy requires psychometric testing to confirm a diagnosis. Treatment consists of identifying and treating the underlying cause (e.g., GI bleeding) and pharmacotherapy with disaccharide laxatives (e.g., lactulose) and/or rifaximin. Liver transplant is the only curative therapy.

Definitiontoggle arrow icon

Brain dysfunction (e.g., fluctuations in mental status and cognitive function) in the presence of liver insufficiency (e.g., cirrhosis) [2][3]

Epidemiologytoggle arrow icon

Epidemiological data refers to the US, unless otherwise specified.

Etiologytoggle arrow icon

Pathophysiologytoggle arrow icon

Clinical featurestoggle arrow icon

Symptoms are usually reversible and may be nonspecific.

  • Fatigue, lethargy, apathy
  • Altered levels of consciousness, ranging from mild confusion to stupor or coma
  • Disoriented
  • Irritability
  • Memory loss
  • Impaired sleeping patterns
  • Multiple neurological and psychiatric disturbances
  • Socially aberrant behavior (e.g., urinating/defecating in public, shouting at strangers)
  • Slurred speech
  • Asterixis
  • Muscle rigidity

Classificationtoggle arrow icon

Classification is generally based on the following four parameters: [2][5]

  • Underlying disease
  • Severity: graded according to the West Haven criteria based on clinical features [2][5]
    • Covert hepatic encephalopathy: symptoms minor/absent; abnormalities are present on neuropsychological and/or neurophysiological testing
    • Overt hepatic encephalopathy: symptoms present and reproducible; corresponds with West Haven criteria grade II or higher
  • Time course
    • Episodic
    • Recurrent
    • Persistent
  • Presence of precipitating factors: nonprecipitated or precipitated

Diagnosticstoggle arrow icon

General principles [2][6]

Initial evaluation [2][7]

Additional evaluation

Serum ammonia levels are usually elevated in hepatic encephalopathy. However, elevated levels are not diagnostic and the magnitude of elevation does not correlate with the degree of encephalopathy. [7]

Treatmenttoggle arrow icon

General measures [2]

Identification and treatment of infection and/or bleeding is critical, as these precipitants are associated with high mortality. [5]

Pharmacotherapy [2]

Oral administration of medications may not be safe in patients with overt hepatic encephalopathy at risk of aspiration. Consider alternative administration routes.

Liver transplant [5]

  • Only definitive treatment option [5]
  • Consider in all patients with recurrent or persistent HE
  • Referral for evaluation by transplant center is recommended for all patients with first episode of overt hepatic encephalopathy

Disposition [5]

Prevention [2][5]

Referencestoggle arrow icon

  1. $Contributor Disclosures - Hepatic encephalopathy. None of the individuals in control of the content for this article reported relevant financial relationships with ineligible companies. For details, please review our full conflict of interest (COI) policy:.
  2. Vilstrup H. Hepatic Encephalopathy in Chronic Liver Disease: 2014 Practice Guideline by the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases. J Hepatol. 2014; 61 (3): p.642-659.doi: 10.1016/j.jhep.2014.05.042 . | Open in Read by QxMD
  3. Mansour D, McPherson S. Management of decompensated cirrhosis.. Clin Med. 2018; 18 (Suppl 2): p.s60-s65.doi: 10.7861/clinmedicine.18-2-s60 . | Open in Read by QxMD
  4. Frederick RT. Current concepts in the pathophysiology and management of hepatic encephalopathy.. Gastroenterology & hepatology. 2011; 7 (4): p.222-33.
  5. Ferenci P. Hepatic encephalopathy. Gastroenterol Rep (Oxf). 2017; 5 (2): p.138-147.doi: 10.1093/gastro/gox013 . | Open in Read by QxMD
  6. Vilstrup H, Amodio P, Bajaj J, et al. Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study Of Liver Diseases and the European Association for the Study of the Liver. Hepatology. 2014; 60 (2): p.715-735.doi: 10.1002/hep.27210 . | Open in Read by QxMD
  7. Montagnese S, Rautou PE, Romero-Gómez M, et al. EASL Clinical Practice Guidelines on the management of hepatic encephalopathy. J Hepatol. 2022; 77 (3): p.807-824.doi: 10.1016/j.jhep.2022.06.001 . | Open in Read by QxMD
  8. Swaminathan M, Ellul M, Cross T. Hepatic encephalopathy: current challenges and future prospects. Hepat Med. 2018; Volume 10: p.1-11.doi: 10.2147/hmer.s118964 . | Open in Read by QxMD
  9. Williams R, James OFW, Warnes TW, Morgan MY. Evaluation of the efficacy and safety of rifaximin in the treatment of hepatic encephalopathy. Eur J Gastroenterol Hepatol. 2000; 12 (2): p.203-208.doi: 10.1097/00042737-200012020-00012 . | Open in Read by QxMD

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