What liver function test values are associated with hepatic encephalopathy?

Liver Function Test Values Associated with Hepatic Encephalopathy

Elevated blood ammonia is the primary liver function test value associated with hepatic encephalopathy, but a normal ammonia level in a patient with suspected HE should prompt diagnostic reevaluation. 1, 2

Ammonia Levels and Hepatic Encephalopathy

• Normal blood ammonia levels: ≤35 µmol/L (≤60 µg/dL) 2
• Hyperammonemia definition: ≥50 µmol/L (≥85 µg/dL) in adults 2
• Toxic levels: >200 µmol/L (>341 µg/dL), associated with poor neurological outcomes 2

Studies have shown significantly elevated venous ammonia levels in patients with minimal hepatic encephalopathy (MHE) and spontaneous shunts (82.4 ± 20.3 vs. 47.1 ± 16.7 µmol/L) 3

Important Considerations for Ammonia Testing

• Diagnostic value: While elevated ammonia is characteristic of HE, ammonia levels alone do not add diagnostic, staging, or prognostic value in HE patients with chronic liver disease 1, 2
• Negative predictive value: A normal ammonia level brings the diagnosis of HE into question and warrants reevaluation 1, 2
• Collection technique: Proper collection is critical for accurate measurement:
  • Fasting patient
  • Avoid venous stasis
  • Use EDTA-containing tube
  • Immediate placement on ice
  • Rapid transport to laboratory (within 60-90 minutes) 2

Diagnostic Algorithm for Hepatic Encephalopathy

1. Clinical assessment: HE diagnosis is primarily based on clinical criteria and exclusion of other causes of brain dysfunction 1

   • Use West Haven criteria for grading when temporal disorientation is present (grades >2)
   • Add Glasgow Coma Scale for grades III-IV 1

2. Laboratory testing:

   • Check plasma ammonia (normal value brings HE diagnosis into question) 1
   • Rule out other causes of altered mental status

3. Brain imaging:

   • Perform CT scan or MRI in case of diagnostic doubts or non-response to treatment 1
   • Note: No cerebral imaging can definitively prove HE diagnosis 1

Pathophysiology and Precipitating Factors

Elevated ammonia levels occur due to:

• Reduced functional capacity of hepatocytes
• Decreased activity of urea cycle enzymes
• Portal hypertension creating collateral circulation
• Blood bypassing the liver, preventing ammonia detoxification 2

Common precipitating factors that should be identified and managed:

• Gastrointestinal bleeding
• Infection
• Dehydration
• Constipation
• Excessive protein intake 2, 4

Treatment Approach

Treatment should not be guided exclusively by ammonia levels but should focus on:

1. Identifying and managing precipitating factors 1
2. Ammonia-lowering treatments:
   • Lactulose (oral or rectal) as first-line therapy 1
   • Rifaximin as an add-on to lactulose for prevention of recurrent episodes 1
   • L-ornithine L-aspartate (LOLA) to stimulate the urea cycle 2

Clinical Pearls and Pitfalls

• Pitfall: Relying solely on ammonia levels for diagnosis or treatment decisions
• Pitfall: Improper collection technique leading to falsely elevated ammonia levels
• Pearl: A normal ammonia level should prompt reconsideration of HE diagnosis
• Pearl: Repeated ammonia measurements can help evaluate treatment efficacy 2

While ammonia is the primary liver function test associated with HE, the diagnosis remains clinical, and management should focus on treating precipitating factors and reducing ammonia production/increasing its elimination.