Hepatic Encephalopathy: A Practical Guide to Diagnosis and Treatment

A practical guide to diagnosing, managing, and preventing hepatic encephalopathy.
Abdelwahab Ward, BS Pharm, PharmD

Overview

As a clinical pharmacist, you may be asked about managing hepatic encephalopathy in patients with liver failure. You should suspect hepatic encephalopathy in cirrhotic patients who exhibit subtle changes in mental status, mood, or behavior. Look for early signs such as unsteadiness, frequent falls, poor sleep quality, fluctuating attention, and delayed responses. These patients often present with classic features of liver disease, including jaundice, ascites, and spider angiomata, along with neurological symptoms.

Always evaluate for common precipitating factors, including electrolyte imbalances (hyponatremia, hypokalemia), infections, dehydration, renal failure, gastrointestinal bleeding, and the inappropriate use of sedatives or recreational drugs. Constipation is another overlooked but significant trigger. It’s essential to rule out alternative causes of altered mental function, such as metabolic encephalopathy, intoxication, or intracranial pathology—especially in patients with recent falls, head trauma, or those found unconscious.

Overt hepatic encephalopathy is a clinical diagnosis made after excluding other causes. In certain cases, specialized neuropsychological testing can help detect minimal or covert hepatic encephalopathy, particularly when its presence might impact employment or public safety. Consider bedside tools like the Stroop smartphone application (EncephalApp) or the Animal Naming Test (ANT) for quick assessment in suspected cases.

Hepatic encephalopathy stages

Hepatic encephalopathy progresses through four stages (📊 use MD+Calc)

  • Stage 1 (Minimal to Mild) – Subtle changes in behavior, attention, and sleep patterns. Patients may have mild confusion, irritability, or difficulty with simple tasks.
  • Stage 2 (Moderate) – More noticeable confusion, lethargy, personality changes, and asterixis (flapping hand tremor).
  • Stage 3 (Severe) – Marked confusion, stupor, inability to follow commands, and worsening asterixis.
  • Stage 4 (Coma) – Unresponsive, possible decerebrate posturing, and risk of respiratory failure.

NPS-adv

Management

1. Identify and treat precipitating factors

Exclude alternative causes of altered mental status. Common precipitants include infections, overdiuresis, gastrointestinal bleeding, high oral protein load, and constipation. Narcotics and sedatives worsen encephalopathy by depressing brain function. TIPS procedures may trigger hepatic encephalopathy, necessitating shunt reduction or occlusion.

2. Lower ammonia levels

  • Lactulose: First-line therapy (15–30 mL orally twice daily) to achieve 2–3 soft bowel movements per day
  • Polyethylene glycol (PEG 3350-electrolyte solution): Alternative option (4 L orally or via nasogastric tube over 4 hours) for a more rapid response
  • Nonabsorbable antibiotics:
    • Rifaximin (550 mg twice daily)
    • Neomycin (500 mg–1 g three times daily)
    • Metronidazole (250 mg two to four times daily)
  • Emerging therapies: L-ornithine-L-aspartate, benzoate, glycerol phenylbutyrate

3. Secondary prophylaxis

After resolution of an episode, continue lactulose for secondary prevention. If the precipitating factor is well controlled or liver function improves, prophylactic therapy may be discontinued.

For recurrent hepatic encephalopathy, rifaximin combined with lactulose reduces recurrence risk. Switching dietary protein from animal to vegetable sources may be beneficial, but chronic protein restriction is unnecessary. Experimental therapies, such as modifying gut microbiota to reduce urease activity, are under investigation. Monitor ammonia-lowering therapies closely. Titrate lactulose to maintain target stool output. Use rifaximin in patients with recurrent episodes. Avoid excessive protein restriction—malnutrition worsens outcomes. Address precipitating factors early to prevent progression.

NPS-adv

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Figure (1)
Management of HE

References

  1. Ferenci P. Hepatic encephalopathy. Gastroenterol Rep (Oxf). 2017;5(2):138-147.
  2. Rogal SS, Hansen L, Patel A, et al. AASLD Practice Guidance: Palliative care and symptom-based management in decompensated cirrhosis. Hepatology. 2022;76(3):819-853.
  3. Juneau J, and Mcguire B. Hepatic Encephalopathy. [online] Available at: https://cdn.intechopen.com/pdfs/35736/Hepatic-encephalopathy.pdf [Accessed 12 Feb. 2025].
  4. 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):715-735.

Abdelwahab Ward, BS Pharm, PharmD