Hepatic Encephalopathy
Basics
Description
- Reversible altered mental and neuromotor functioning in association with acute or chronic liver disease and/or portosystemic shunting
- Wide spectrum of neurologic/psychiatric abnormalities ranging from subclinical alterations to coma: Prominent features are confusion, impaired arousability, and a “flapping tremor” (asterixis).
Epidemiology
Male = female (reflects prevalence of underlying liver disease)
Incidence
- The risk of first episode of overt hepatic encephalopathy (HE) is 5–25% within 5 years of cirrhosis diagnosis.
- Posttransjugular intrahepatic portosystemic shunt (TIPS), median cumulative 1-year incidence of overt HE is 10–50%
Prevalence
- May occur at any age; parallels the age predominance of fulminant liver disease: peaks in the 40s (Cirrhosis peaks in the late 50s.)
- Occurs in all cases of fulminant hepatic failure or acute liver failure (ALF); overt HE occurs in 30–45% of cirrhotic patients; present in ~50% of patients requiring liver transplantation
Etiology and Pathophysiology
- There is no defined pathophysiology for the development of HE. However, elevated serum levels of ammonia (hyperammonemia) correlate with the severity of HE, suggesting a central role of ammonia as a neurotoxin.
- Classifications based on four factors have been proposed:
- According to the underlying disease:
- Type A: resulting from ALF; type B: resulting from portosystemic bypass or shunting in absence of inherent liver disease; type C: resulting from cirrhosis
- According to severity of manifestation:
- West Haven classification: Convert to grades I to IV (see “Physical Exam” section).
- According to time course:
- Episodic HE; recurrent HE = >1 episode occurring within 6 months; persistent HE = persistent behavioral alterations interspersed with relapses of overt HE
- According to precipitating factors:
- Nonprecipitated; precipitated
- According to the underlying disease:
- Several metabolic factors implicated in HE based on the failure of the liver to detoxify noxious CNS agents (e.g., ammonia, mercaptan, octopamine, tyramine, fatty acids, lactate, manganese)
- Increased aromatic and reduced branched chain amino acids in blood may act as false neurotransmitters, possibly interacting with the γ-aminobutyric acid (GABA) receptor to cause clinical symptoms
- HE presents most commonly in patients with long-standing cirrhosis and spontaneous shunting of intestinal blood through collateral vessels or surgical portacaval shunts.
- Asterixis is the inability to maintain a particular posture due to metabolic encephalopathy. Abnormal diencephalic function leads to the characteristic liver flap noted when the arms and wrists are held in extension.
Genetics
- Unknown/unclear
- Conditions that predispose an individual to developing chronic liver disease such as cystic fibrosis, α1-antitrypsin deficiency, hemochromatosis, and Wilson disease can contribute to the development of HE.
- A glutaminase gene variation that increases enzyme activity may predispose patients to develop HE.
Risk Factors
In patients with underlying liver disease, precipitating factors include the following:
- Electrolyte disturbance (Na+, K+, Mg2+ most common); infection (overt or occult, including spontaneous bacterial peritonitis [SBP]); GI hemorrhage
- Use of sedative (e.g., benzodiazepines) or opiate drugs; fluid abnormalities including from diuretic overuse
- TIPS—a radiologically inserted shunt to lower portal pressure—elderly patients and those with worse liver function are at increased risk of developing HE following TIPS.
General Prevention
- Recognize early signs and seek prompt treatment. Avoid nonessential medications, particularly opiates, benzodiazepines, and sedatives. Consider lactulose therapy as secondary prophylaxis for recurrence of overt HE.
- For patients who have already experienced bouts of overt HE while on lactulose, lactulose + rifaximin is the best-documented agent to maintain remission (1).
Commonly Associated Conditions
- Cirrhosis; portal hypertension; may occur as a complication of acute fatty liver of pregnancy
- Occurs rarely in patients with a portacaval shunt accompanied by normal liver function
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Citation
Domino, Frank J., et al., editors. "Hepatic Encephalopathy." 5-Minute Clinical Consult, 33rd ed., Wolters Kluwer, 2025. Medicine Central, im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/117471/0.5/Hepatic_Encephalopathy.
Hepatic Encephalopathy. In: Domino FJF, Baldor RAR, Golding JJ, et al, eds. 5-Minute Clinical Consult. Wolters Kluwer; 2025. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/117471/0.5/Hepatic_Encephalopathy. Accessed October 15, 2024.
Hepatic Encephalopathy. (2025). In Domino, F. J., Baldor, R. A., Golding, J., & Stephens, M. B. (Eds.), 5-Minute Clinical Consult (33rd ed.). Wolters Kluwer. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/117471/0.5/Hepatic_Encephalopathy
Hepatic Encephalopathy [Internet]. In: Domino FJF, Baldor RAR, Golding JJ, Stephens MBM, editors. 5-Minute Clinical Consult. Wolters Kluwer; 2025. [cited 2024 October 15]. Available from: https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/117471/0.5/Hepatic_Encephalopathy.
* Article titles in AMA citation format should be in sentence-case
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