What are the complications in the brain associated with rising Liver Function Tests (LFTs) and how are they managed?

Brain Complications Associated with Rising Liver Function Tests

Hepatic encephalopathy (HE) is the primary brain complication associated with rising liver function tests, requiring prompt identification and management of precipitating factors to reduce morbidity and mortality.

Pathophysiology and Clinical Presentation

• Hepatic encephalopathy occurs when liver dysfunction leads to accumulation of neurotoxic substances, primarily ammonia, causing cerebral edema and intracranial hypertension in severe cases 1, 2
• HE presents along a spectrum from minimal cognitive changes (covert HE) to severe alteration in consciousness (overt HE), graded using the West Haven criteria 1
• Rising LFTs indicate worsening liver function which increases risk of HE through impaired ammonia metabolism and portosystemic shunting 1
• Molecular mechanisms include:
  • Excessive accumulation of glutamate causing excitotoxicity in acute liver failure 3
  • Increased inhibitory GABA neurotransmission in chronic liver failure 3
  • Accumulation of osmolytes like glutamine in astrocytes contributing to cerebral edema 3

Precipitating Factors

• All patients with HE have at least one precipitating factor, with 82% having multiple concomitant factors 4
• Common precipitating factors include:
  • Infections (64% of cases) - particularly spontaneous bacterial peritonitis, urinary tract infections, and pneumonia 5, 4
  • Acute kidney injury (63%) 4
  • Medications (41%) - particularly sedatives, diuretics 6, 4
  • Gastrointestinal bleeding (36%) 4
  • Electrolyte disturbances - especially hyponatremia (22%) 6, 4
  • Constipation 1
  • Transjugular intrahepatic portosystemic shunts (TIPS) (12%) 6, 4

Diagnostic Approach

• Brain imaging (CT) should be performed in patients with chronic liver disease and unexplained alteration of brain function to exclude structural lesions 1
• Neuropsychological/neurophysiological testing is recommended for diagnosis of covert HE 1
• For patients with grades III-IV HE (West Haven criteria), the Glasgow Coma Scale should be added for monitoring 1
• Electroencephalogram (EEG) may show changes but cannot differentiate between HE and other causes of encephalopathy 1
• Normal blood ammonia level in a patient suspected of HE requires consideration of alternative diagnoses 1

Management Algorithm

For Covert HE (Grades I-II):

1. Transfer to liver transplant facility and consider listing for transplantation 1
2. Identify and address precipitating factors:
   • Treat infections with appropriate antibiotics 1, 5
   • Correct electrolyte disturbances, particularly hyponatremia 1, 6
   • Stop or adjust medications that may worsen HE (sedatives, diuretics) 6
   • Control gastrointestinal bleeding 1
   • Treat constipation 1
3. Initiate lactulose therapy (potentially beneficial) 1
4. Avoid sedation if possible 1
5. Monitor neurological status frequently for signs of deterioration 1

For Overt HE (Grades III-IV):

1. Continue all management strategies listed above 1
2. Intubate trachea for airway protection (may require minimal sedation) 1
3. Elevate head of bed to 30 degrees 1
4. Consider placement of ICP monitoring device in selected cases 1
5. Treat seizures immediately if they occur 1
6. For severe elevation of ICP or signs of herniation:
   • Administer mannitol 1
   • Consider short-term hyperventilation for impending herniation 1
7. Target serum sodium between 140-145 mmol/L (hypertonic saline may be used) 1
8. Monitor glucose closely (at least every 2 hours) and correct hypoglycemia 1
9. Avoid osmotic laxatives (lactulose) or non-absorbable antibiotics (rifaximin) in acute liver failure 1

Post-Discharge Management

• Confirm neurological status before discharge and inform caregivers that status may change 1
• Plan outpatient consultations to adjust treatment and prevent recurrence of precipitating factors 1
• Educate patients and relatives about:
  • Medication effects and potential side effects 1
  • Importance of adherence 1
  • Early signs of recurring HE 1
  • Actions to take if recurrence occurs 1
• Monitor for neurological manifestations to adjust treatment and investigate presence/degree of HE 1
• Address socioeconomic implications, which may include decline in work performance, impaired quality of life, and increased risk of accidents 1

Important Caveats

• Multiple concomitant precipitating factors are associated with poor prognosis and increased mortality 4
• Avoid attributing fever solely to liver disease; always search for underlying infections 5
• Brain imaging results in HE are often disappointing but necessary to exclude other causes 1
• Patients with HE often have multiple factors contributing to their clinical presentation 5
• The term "brain failure" should be replaced with "acute encephalopathy" in accordance with international guidelines on delirium 1
• Patients should not be classified based on the etiology of their underlying liver disease, as different etiologies can impact brain function through various mechanisms 1