Acute Liver Failure (ALF)

Clinical Definition

• Diagnosis Criteria for ALF:

  • Clinical or laboratory evidence of acute liver injury or hepatitis (elevated LFTs)
  • Coagulopathy (INR ≥ 1.5)
  • Encephalopathy (graded by West Haven criteria)
  • Duration: < 26 weeks
  • No pre-existing cirrhosis
  • Notable exceptions: Wilson disease, hepatitis B reactivation, autoimmune hepatitis

• West Haven Criteria for Hepatic Encephalopathy (HE):

  • Grade 1: Subtle behavioral changes and altered sleep-wake cycle
  • Grade 2: Onset of asterixis, lethargy, disorientation
  • Grade 3: Severe confusion, disorientation, somnolence
  • Grade 4: Coma

• Cerebral Edema Incidence:

  • Grades 1&2: Rare
  • Grade 3: 25-35% incidence
  • Grade 4: 65-75% incidence

Etiology Framework

Vascular Causes

• Budd-Chiari Syndrome: Thrombosis of the hepatic vein
  • Associated with polycythemia, malignancy, pro-thrombotic states
• Ischemic Liver Injury (Shock Liver): Low-flow arterial states
  • Shock acronym: Septic, Hypovolemic, Obstructive, Cardiogenic, Combined
• Workup: Liver ultrasound with Dopplers, broad cultures, transthoracic echocardiogram

Parenchymal Causes

• Toxic:

  • Acetaminophen overdose (45% cases)
  • Drug-induced (variety of medications and supplements)
  • Other toxins: Cocaine, alcohol, Amanita phalloides
  • Workup: Acetaminophen level, urine & serum toxicology, medication review

• Viral:

  • Hepatitis A, B (8% USA), D, E (endemic areas: Russia, Pakistan, Mexico, India)
  • Herpesviruses: HSV, VZV, CMV, EBV
  • Workup: Viral serology

• Autoimmune: Autoimmune hepatitis

  • Workup: ANA, Anti-smooth muscle antibody, Anti-LKM antibody, Immunoglobulins (especially IgG)

• Infiltrative: Wilson disease, HLH, malignancy

  • Wilson disease indicator: Hepatic, neurologic, psychiatric abnormalities, bilirubin/alakline phosphatase ratio >2
  • Workup: Ceruloplasmin, ferritin, additional imaging

• Pregnancy-associated: Acute fatty liver of pregnancy, HELLP syndrome

  • Workup: Urine & serum beta-HCG

Common Causes in USA

• Ischemia, acetaminophen, drug-induced, hepatitis B virus, autoimmune (≈80% cases)

Treatment Principles

• ICU Management: Transplant center with GI or hepatology consult
• Standard Care: Airway management, respiratory support, fluid resuscitation, cardiovascular support
• N-acetylcysteine (NAC) Administration:
  • For both acetaminophen and non-acetaminophen induced ALF
  • Study: Increased transplant-free survival for Grade 1&2 HE (40% vs 27%)
• Acyclovir: Initiate until HSV and VZV ruled out

Potential Complications and Interventions

Cerebral Edema

• Pathophysiology: Hyperammonemia leads to astrocyte swelling, cerebral edema, intracranial hypertension (ICH)
• Ammonia Levels:
  • <75: Rare ICH

  • 100: Risk of high-grade HE

  • 200: Predicts ICH development

• Monitoring: Q1 hour neuro checks, head CT for mental status changes
• Interventions: Elevate head 30°, even fluid balance (CRRT), hyperventilation, hypertonic saline, mannitol

Hypoglycemia

• Cause: Liver stores glycogen, site of gluconeogenesis
• Monitoring: Frequent blood glucose checks
• Treatment: Dextrose infusion

Coagulopathy

• Liver Function: Synthesizes clotting factors (except factor VIII), anticoagulants (protein C, S)
• Monitoring: Thromboelastogram (TEG)
• Interventions: Only correct if bleeding or for invasive procedures

Infection Risk

• Liver Role: Kupffer cells, key in innate immunity
• Protocol: Culture at presentation and for any infection concern, aggressive treatment, low threshold for empiric antibiotics

Summary

• Definition: Elevated LFTs + coagulopathy + encephalopathy without cirrhosis, <26 weeks
• Framework: Vascular vs. parenchymal causes
• Treatment: ICU, NAC for all, supportive measures
• Complications: Cerebral edema, hypoglycemia, coagulopathy, infection