Hepatic Encephalopathy: A Rapid Review

Hepatic Encephalopathy rapid review
Cite this article as:
Thiagalingam, P. Hepatic Encephalopathy: A Rapid Review, First10EM, October 18, 2021. Available at:

In the Rapid Review series, we (somewhat) briefly review the key points of a clinical review paper (or three). The topic this time: hepatic encephalopathy.

This is a guest post by Punithan Thiagalingam (@_punithant), an MD student at the University of Toronto. He has a background in biochemistry and development of novel cancer biotechnology platforms. His areas of interest include EBM, FOAMed, emergency medicine, and working to rectify health disparities impacting marginalized patient populations. 

 The papers:

Montrief, T., Koyfman, A., & Long, B. (2019). Acute liver failure: A review for emergency physicians. The American Journal of Emergency Medicine, 37(2), 329–337. https://doi.org/10.1016/j.ajem.2018.10.032

Long, B., & Koyfman, A. (2018). The Emergency Medicine Evaluation and management of the patient with cirrhosis. The American Journal of Emergency Medicine, 36(4), 689–698. https://doi.org/10.1016/j.ajem.2017.12.047

Acharya, C., & Bajaj, J. S. (2018). Current management of Hepatic encephalopathy. American Journal of Gastroenterology, 113(11), 1600–1612. https://doi.org/10.1038/s41395-018-0179-4

What is hepatic encephalopathy?

Hepatic encephalopathy is a neurologic manifestation of acute liver failure, often in patients with decompensated cirrhosis. It is associated with long standing cognitive issues that get worse with each episode.


The pathophysiology is not fully understood, but in short, ammonia (and other toxins) which are normally metabolized by the liver build up in the serum. When they reach the brain, they increase glutamine production causing cerebral edema and encephalopathy. Cerebral edema and encephalopathy are worsened by inflammation, hemodynamic instability, and hypotension.

What are the precipitants of hepatic encephalopathy?

  1. Increased nitrogen: GI Bleed, infection
  2. Decreased clearance of toxins: renal failure, constipation, non-adherence with medications
  3. Neurotransmitter alteration: alcohol, sedatives, hypoglycemia, hypoxemia

What about dietary intake of protein?

A high protein diet may increase nitrogen levels contributing to hepatic encephalopathy. However, the evidence for limiting protein in the diet is not strong and the review articles we consulted had differing opinions on this practice. It is important to note that patients with cirrhosis may also be at risk for sarcopenia, so optimizing nutritional status is important.

How do patients present?

Hepatic encephalopathy is graded on a scale, with higher grade corresponding to a worse prognosis.

  • Grade 1: Altered mood/behaviour (depression, euphoria), anxiety, decreased attention, hypersomnia/insomnia
  • Grade 2: Disorientation (time, place), apathy, lethargy, slurred speech, asterixis
  • Grade 3: Incoherent speech, somnolence
  • Grade 4: Comatose, unresponsive to verbal or pain stimuli

Key Points on History

  • Hepatic encephalopathy is a diagnosis of exclusion. Rule out other causes of altered mental status: medications, substances, withdrawal, sepsis, renal failure, head injury.
  • Determine the likely etiology of liver disease.
  • Ask about the baseline health and baseline neurologic status of the patient.
  • Assess chronic management: most recent endoscopy, weight, medications, adherence to medications, average number of bowel movements per day.
  • Ask about prior complications: infections, varices, encephalopathy.
  • Screen for a cause of decompensation: infectious symptoms, GI bleeding, constipation, urinary symptoms, TIPS procedure.

How do you test for asterixis?

You can ask the patient to hold their arms out in front of them, with the wrists extended, and the fingers spread apart. They will be unable to maintain tone at the wrists resulting in brief, involuntary, irregular, and asynchronous downward movements. This can be much more subtle than the dramatic “hand flapping” described in textbooks.

What about an ammonia level?

Ammonia levels are not indicated for the diagnosis of hepatic encephalopathy. Ammonia will be normally elevated in liver disease due to decreased clearance. It will not change management in the emergency setting. Choosing Wisely Canada states: “Don’t order serum ammonia to diagnose or manage hepatic encephalopathy (HE). High blood-ammonia levels alone do not add any diagnostic, staging, or prognostic value in HE patients known to have chronic liver disease.”

What is the initial ED management?

  1. As always, manage the ABCs. Altered mental status and hematemesis from variceal hemorrhage are important considerations.
  2. Assess for focal neurologic signs, signs of trauma, or other indications for a CT head. Perform a detailed neurologic exam, including presence of asterixis.
  3. If there is ascites with a drainable fluid collection, perform a paracentesis to exclude SBP.
  4. Consider if antibiotics are required for SBP prophylaxis or other infection.
  5. Consider empiric treatment of Wernicke ecephalopathy: thiamine 500 mg IV.
  6. Begin specific treatment for suspected hepatic encephalopathy (discussed below).
  7. Supportive care: correct fluid, electrolyte, and glucose deficits. Potassium is particularly important. Even mild hypokalemia can decrease ammonia excretion, so correcting hypokalemia is thought to decrease ammonia levels in patients with HE.
  8. Avoid long acting sedative and deliriogenic medications. 

So… what’s the treatment?

Lactulose is the first line to encourage bowel movements (although newer evidence suggests PEG3350 may be superior). It is given orally at a dose of 10-30g (15-45mL) every 1-2 hours until there is a bowel movement. In patients who cannot tolerate PO medication, enemas are possible. After a bowel movement is achieved, continue with lactulose 2-4 times per day targeting 3-4 bowel movements per day.

Rifaximin is a non-absorbable antibiotic. It is used as a second line or in combination with lactulose. Emerging evidence suggests rifaximin monotherapy is superior to lactulose monotherapy. Currently this medication is used as maintenance therapy in patients with recurrent hepatic encephalopathy. 

Neomycin has also been studied and is as effective as lactulose but is rarely used given its nephrotoxicity, ototoxicity, and neurotoxicity.

What are complications to be aware of? 

Intracranial hypertension (ICH) can result if cerebral edema goes untreated. Signs of ICH are systolic hypertension, bradycardia, and irregular respirations. Similarly, seizures can be seen in these patients. 

What is the prognosis?

Unfortunately, the prognosis of hepatic encephalopathy is very poor. After a first episode, the 1 year survival rate is only 35-45%. 


Patients with Grade 1 HE, who respond to initial treatment and have supports in place at home may be discharged with outpatient follow-up. However, most patients with Grade 1 or 2 HE will require admission. Grade 3 or 4 HE require ICU level care.

Other FOAMed

EM Cases Episode 148: Liver Emergencies

First10EM approach to an unconscious patient

IBCC: Critical hepatic encephalopathy

Leave a Reply