Acute liver failure

ALF Defined - When the Liver Fails Fast

• Rapid, severe liver injury in a previously healthy individual, marked by:
  • Hepatic Encephalopathy (HE): Any degree of altered mental status.
  • Impaired Synthesis: Coagulopathy with an INR ≥ 1.5.
• Occurs in patients without pre-existing cirrhosis; illness duration is < 26 weeks.

⭐ The hallmark of ALF is the triad of coagulopathy, encephalopathy, and the absence of underlying chronic liver disease. Acetaminophen toxicity is the most common cause in the United States.

Presentation & Dx - Jaundice, Confusion, Crisis

• Clinical Triad:
  • Jaundice: Scleral icterus, ↑ bilirubin.
  • Hepatic Encephalopathy (HE): Confusion, personality changes, asterixis (liver flap). Graded I-IV.
  • Coagulopathy: Bleeding, bruising. Defined by INR > 1.5 without prior cirrhosis.
• Key Labs:
  • ↑↑ AST/ALT (often > 1000 IU/L)
  • ↑ Ammonia (correlates with HE severity)
  • Hypoglycemia

⭐ Acetaminophen toxicity is the leading cause of acute liver failure in the United States.

ALF Management - The Critical First Steps

• ABCs First: Secure airway, breathing, and circulation. Intubate for Grade ≥III encephalopathy to protect against aspiration.
• Transfer: Immediately transfer to an ICU at a liver transplant center.
• Initial Interventions:
  • IV Fluids: Judicious use to maintain MAP >75 mmHg (cerebral perfusion).
  • Hypoglycemia: Monitor glucose hourly; give IV dextrose if glucose <60 mg/dL.
  • Coagulopathy: Correct with FFP/Vitamin K only if actively bleeding.

⭐ NAC for All: N-acetylcysteine (NAC) is given to nearly all ALF patients, regardless of etiology, as it improves systemic redox state and transplant-free survival.

Systemic Havoc - ALF's Complication Cascade

• Cerebral Edema & ↑ ICP: Leading cause of death. Mannitol, hypertonic saline. Goal: ICP < 20 mmHg, CPP > 60 mmHg.
• Coagulopathy: ↓ Synthesis of clotting factors (II, V, VII, IX, X). INR ≥ 1.5. High bleeding risk.
• Hemodynamic Instability: Systemic vasodilation, ↓ SVR, high-output state mimicking septic shock.
• Renal Failure: Acute kidney injury (AKI) is common. Hepatorenal syndrome (HRS) is a grim sign.
• Infections: Bacterial/fungal infections are frequent triggers and complications.

⭐ Grade III/IV hepatic encephalopathy carries the highest risk for cerebral edema and subsequent brainstem herniation.

Transplant Criteria - The Ultimate Lifeline

• King's College Criteria (KCC): Key for determining transplant need in ALF. Different criteria for acetaminophen vs. non-acetaminophen causes.
  • Acetaminophen-induced ALF:
    • Arterial pH < 7.3 (after resuscitation) OR
    • All three: INR > 6.5, Creatinine > 3.4 mg/dL, Grade III-IV encephalopathy.
  • Non-Acetaminophen ALF:
    • INR > 6.5 OR
    • Any 3: Age <10/>40, unfavorable etiology, jaundice >7 days before encephalopathy, INR > 3.5, Bilirubin > 17.5 mg/dL.

⭐ While KCC is classic, the MELD score is also frequently used, and a high MELD score ( >30) is a strong predictor of mortality and indication for transplant listing.

High-Yield Points - ⚡ Biggest Takeaways

• Acute liver failure is defined by hepatic encephalopathy and an INR ≥1.5 in a patient without pre-existing cirrhosis.
• Acetaminophen toxicity is the most common cause in the U.S.; always check an acetaminophen level.
• The classic presentation triad is jaundice, coagulopathy, and encephalopathy.
• Cerebral edema is the most life-threatening complication, causing intracranial hypertension.
• Management requires ICU-level care, treating the underlying cause (e.g., N-acetylcysteine), and urgent evaluation for liver transplantation.