What are the diagnosis and treatment options for a patient with suspected hepatic encephalopathy?

Hepatic Encephalopathy: Diagnosis and Treatment

Diagnosis

Hepatic encephalopathy is diagnosed by excluding other causes of altered mental status in patients with liver disease, using clinical criteria supplemented by ammonia levels and brain imaging when indicated. 1

Clinical Assessment

• Grade overt HE using the West Haven Criteria (grades 0-4), which classifies severity from minimal changes to coma, and add the Glasgow Coma Scale for patients with grades 3-4 encephalopathy 1, 2
• Perform a focused neurological examination assessing orientation, asterixis (flapping tremor), cognitive function, motor/sensory function, and cranial nerves 3
• Classify HE as either overt (OHE)—diagnosed by clinical symptoms alone—or covert (CHE)—requiring specialized cognitive testing 1

Laboratory Testing

• Measure venous blood ammonia levels using proper technique (fasting patient, avoid venous stasis, EDTA tube on ice immediately), recognizing that while elevated ammonia supports the diagnosis, a normal ammonia level in suspected HE mandates reevaluation for alternative diagnoses 1, 3, 2
• Ammonia levels do not correlate with HE severity or prognosis, but can be useful for monitoring treatment response 1
• Obtain complete blood count, comprehensive metabolic panel, inflammatory markers, and coagulation studies to identify precipitating factors 3

Brain Imaging

• Perform CT or MRI brain imaging during the first episode of HE, with new focal neurological signs, or when diagnosis is uncertain, as cirrhotic patients have a 5-fold increased risk of intracerebral hemorrhage with indistinguishable symptoms 1, 3, 2
• Brain imaging does not confirm HE diagnosis but excludes alternative pathology 1, 3

Testing for Covert HE

• Screen for covert HE using validated neuropsychological tests when patients have impaired quality of life, employment concerns, or safety implications (e.g., driving) 1
• Use the Animal Naming Test as a bedside screening tool (patients list animal names for 1 minute; <20 names suggests covert HE) 1, 3
• For formal diagnosis, employ at least two validated tests: paper-pencil (Psychometric Hepatic Encephalopathy Score) plus computerized tests (Critical Flicker Frequency) or neurophysiological tests (EEG) 1, 3

Differential Diagnosis

Systematically exclude: electrolyte disorders (hyponatremia, hypokalemia), hypoglycemia, uremia, drug intoxication (benzodiazepines, opioids), intracranial hemorrhage, Wernicke-Korsakoff syndrome, and infections 1, 3

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Treatment

Immediately initiate lactulose while simultaneously identifying and treating precipitating factors, which are present in 80-90% of cases and often resolve HE when corrected. 1, 2

Immediate Management

• Protect the airway in patients with grade 3-4 HE due to aspiration risk; these patients require ICU-level care 1, 2
• Start lactulose immediately (15-30 mL orally 2-3 times daily) while diagnostic workup proceeds, unless a clear alternative diagnosis is identified 2, 4
• Titrate lactulose to achieve 2-3 soft bowel movements per day 1, 2

Identify and Treat Precipitating Factors

The following precipitating factors account for 80-90% of HE episodes and must be systematically addressed: 1, 2

• Gastrointestinal bleeding: Perform endoscopy, check complete blood count and stool for occult blood; treat with transfusion, endoscopic therapy, and vasoactive drugs 1
• Infection: Obtain chest X-ray, urinalysis with culture, blood cultures, and diagnostic paracentesis if ascites present; initiate appropriate antibiotics 1
• Constipation: Assess bowel history and obtain abdominal X-ray; treat with enemas or additional laxatives 1
• Dehydration/renal dysfunction: Check blood pressure, pulse, skin turgor, and renal function; stop or reduce diuretics and provide IV albumin 1
• Electrolyte disorders: Correct hyponatremia, hypokalemia; stop or reduce diuretics 1
• Medications: Discontinue benzodiazepines (consider flumazenil) and opioids (consider naloxone) 1

Pharmacological Treatment

First-line therapy:

• Lactulose (non-absorbable disaccharide) is the primary treatment, achieving recovery in 70-90% of patients by reducing intestinal pH, converting ammonia to non-absorbable ammonium, and providing osmotic laxative effect 1, 4
• FDA-approved dosing: 15-30 mL orally 2-4 times daily, titrated to 2-3 soft stools per day 4

Second-line/adjunctive therapy:

• Add rifaximin 550 mg orally twice daily to lactulose if the patient experiences more than one additional episode of overt HE within 6 months of the first episode 1, 2, 5
• In clinical trials, 91% of patients receiving rifaximin were using concomitant lactulose 5
• Rifaximin has not been studied in patients with MELD scores >25 5

Secondary Prophylaxis

• All patients must receive lactulose as secondary prophylaxis after the first episode of overt HE, continued indefinitely and titrated to 2-3 bowel movements daily 1, 2
• Add rifaximin to lactulose for secondary prophylaxis after more than one episode within 6 months 1, 2

Special Considerations

• Refer patients to a liver transplant center after the first episode of overt HE, as this indicates advanced liver disease and recurrent/persistent HE is an indication for transplantation 1, 2
• Covert HE should be treated with non-absorbable disaccharides to improve quality of life and prevent progression to overt HE 1
• Primary prophylaxis is not routinely recommended except in high-risk patients (e.g., prior to TIPS placement) 1

Common Pitfalls

• Do not rely solely on ammonia levels for diagnosis or monitoring—they do not correlate with severity or prognosis 1
• Do not restrict dietary protein—this worsens malnutrition without improving outcomes; maintain adequate protein intake (1.2-1.5 g/kg/day) 1
• Do not use neomycin as first-line therapy due to nephrotoxicity and ototoxicity risks; it is reserved for refractory cases 6, 7
• Do not overlook precipitating factors—simply correcting these resolves HE in many cases without escalating pharmacotherapy 1, 2