Hepatic Encephalopathy

Snapshot

• A 45-year-old man with a history of alcoholic cirrhosis is found on the sidewalk with altered mental status. He is brought in to the emergency room by the police. He has had multiple similar visits for intoxication. This time, however, he is noted to be markedly lethargic and jaundiced. On physical exam, he has pronounced asterixis, ascites, and other signs of liver disease such as telangiectasias and palmar erythema. Laboratory evaluation reveals negative serum alcohol levels but elevated ammonia and liver enzymes. A hepatic ultrasound shows a hyperechoic mass in his liver, which is concerning for malignancy in the setting of chronic cirrhosis and was thought to be the possible trigger for his episode of hepatic encephalopathy.

Introduction

• Overview
  • a reversible complication of liver failure characterized by altered mental status and asterixis
  • often precipitated by acute stressors such as dehydration or infection
• Epidemiology
  • incidence
    • 30-40% of patients with cirrhosis
  • risk factors
    • alcohol use
    • hepatitis
• Etiology
  • acute triggers
    • dehydration
    • infection
    • gastrointestinal bleed
    • fluid and electrolyte abnormalities
    • sedatives
    • hepatocellular carcinoma
    • transjugular intrahepatic portosystemic shunt (TIPS)
• Pathogenesis
  • mechanism 
    • ↓ ammonia clearance due to liver dysfunction
      • ammonia is normally metabolized in the liver to urea, which is easily excreted
    • portosystemic shunts causing blood to bypass the liver
    • ammonia is neurotoxic 
      • crosses blood-brain barrier and is converted to glutamine, which is an osmolyte and promotes swelling of brain cells 
      • this leads to cerebral edema
      • alteres neurotransmitter function
• Associated conditions
  • acute liver failure
  • cirrhosis
    • other complications of cirrhosis include portal hypertension, esophageal varices, and hepatocellular carcinoma
• Prognosis
• hepatic encephalopathy is reversible

Classification

• Classification by underlying disease
  • type A
    • acute liver failure
  • type B
    • portosystemic bypass or shunting with preserved liver function
  • type C
• cirrhosis

Presentation

• Symptoms
  • common symptoms
    • mood changes
    • slow to respond
    • unsteadiness
• Physical exam
  • inspection
    • signs of liver disease
      • jaundice
      • ascites
      • spider angiomata
      • palmar erythema
    • asterixis
      • flapping tremor of wrists
    • altered mental status
• coma/stupor in severe cases

Imaging

• CT or MRI of the head
  • indication
    • rule out intracranial hemorrhage or mass as a cause of encephalopathy
  • findings
• cerebral edema

Studies

• Serum labs
  • ↑ ammonia
  • also check
    • liver function panel
    • blood urea nitrogen
• electrolytes

Differential

• Other metabolic encephalopathies
  • diabetic ketoacidosis
    • distinguishing factor
      • hyperglycemia with ketones in the blood and anion gap metabolic acidosis
  • uremic encephalopathy
    • distinguishing factor
      • elevated urea and normal ammonia
  • acute alcoholic intoxication
    • distinguishing factor
• elevated blood alcohol level

Treatment

• Nonoperative
  • correct precipitating factor and electrolyte derangements 
  • lactulose 
    • mechanism
      • gastrointestinal flora degrades lactulose into lactic acid and acetic acid, which results in the clearance of ammonia 
    • indication
      • treatment and prevention
  • rifaximin
    • mechanism
      • ↓ bacteria that produce ammonia
    • indication
• treatment and prevention alongside lactulose

Complications

• Persistent learning impairment