Diagnosis

Hepatic encephalopathy

Etiology

Cause (World Health Congress of Gastroenterology Criteria) [ura]

• Type A: Acute liver failure

• Type B: Portosystemic shunt allowing blood to bypass the liver (without liver failure)

• Type C: Cirrhosis of the liver

Precipitating factors [ura]

• Infection

• Dehydration (diuretics, diarrhea, vomiting, or excessive paracentesis)

• Electrolyte depletion (hyponatremia, hypokalemia, Mg)

• Drugs (benzodiazepine, opioid, antidepressant, antipsychotic, salicylate, NSAIDs)

• Alcohol

• GI bleed

• Constipation

• Excess dietary protein

• Kidney dysfunction and azotemia

• TIPS

Pathophysiology [ura]

1. Colonic bacteria and mucosal enzymes break down dietary proteins --> releasing ammonia in the GI tract

2. Ammonia is absorbed into the portal circulation --> converted into urea in the liver.

3. Liver failure or systemic shunting --> ammonia accumulate in the systemic circulation

4. Hyperammonemia --> astrocyte swelling/dysfunction

   • Astrocytes maintain electrolyte homeostasis, provide nutrients and neurotransmitter precursors to neurons

5. Hyperammonemia --> impair neurotransmission --> hepatic encephalopathy:

   • Early phase: disrupted sleep-wake pattern (sleep during daytime, awake at night)

   • Intermediate stage: confusion, lethargy, and personality changes

   • Advanced stage: coma

Complications [ura]

• Agitation

• Seizure

• Residual cognitive impairment

• Cerebral edema and brain herniation

• Mortality

Epidemiology

Incidence per 100.000 [mc4][rtu][utr][mzf][gee][w32]

Approach

• Blood test: ammonia, liver function tests, electrolyte levels, complete blood count, kidney function tests, thyroid-stimulating hormone, procalcitonin, CRP

• Arterial blood gas

• Blood culture

• EEG

• CT caput

• CT abdomen

• Ultrasound abdomen

West Haven Criteria [ura]

• Grade 1

  • Trivial lack of awareness

  • Euphoria or anxiety

  • Shortened attention span and impaired ability to perform simple calculations (addition or subtraction)

• Grade 2

  • Lethargy or apathy

  • Minimal disorientation to time or place

  • Subtle personality changes

  • Inappropriate behavior

• Grade 3

  • Somnolence to semi-stupor, but responsive to verbal stimuli

  • Confusion

  • Gross disorientation

• Grade 4

  • Coma

Treatment

The goals of treatment: [n7s]

• Treating the precipitating factor(s)

• Improving mental status

The treatment and management of HE depend on its severity and acuity: [ksd]

1. Acute episode:

   • Lactulose (non-absorbable disaccharide) is first-line therapy (self-titrate to achieve 2 to 4 soft bowel movements daily)

   • Rifaximin (non-absorbable oral antibiotic)

   • L-ornithine L-aspartate i.v. (oral branched-chain amino acids)

   • Ornithine Phenylacetate

   • Glycerol Phenylbutyrate

   • Correct zinc deficiency (low levels of zinc lead to impairment of urea cycle enzymes and glutamine synthetase, thus leading to increased ammonia levels)

   • Albumin Dialysis

   • Alternative treatment: neomycin, metronidazole (ototoxicity, nephrotoxicity, and antibiotic resistance)

2. Prophylaxis: [ura]

   • Lactulose

   • Rifaximin

   • Probiotics

   • Nutrition: many small meals to prevent fasting (may increase ammonia)

     • Energy: 35 to 40 kcal/kg/d

     • Protein: 1.2 to 1.5 g/kg/d

3. Liver transplantation is the definitive surgery

Differential diagnoses

Alcohol intoxication, Brain abscess, Brain tumor, Drug side effects, Encephalitis, Hypercalcemia, Hypercarbia, Hyperkalemia, Hypernatremia, Hypocalcemia, Hypoglycemia, Hypokalemia, Hyponatremia, Hypoxemia, Inherited urea cycle disorder, Intracerebral hemorrhage, Meningitis, Postseizure encephalopathy, Renal failure, Stroke, Subdural hematoma, Ureterosigmoidostomy, Wernicke encephalopathy