11.3 Acute Liver Failure, Hepatic Encephalopathy & Cirrhotic Complications

11.3 Acute Liver Failure, Hepatic Encephalopathy & Cirrhotic Complications

Clinical Scenario: A 29-year-old female presents with acute jaundice and encephalopathy 72 hours after an intentional acetaminophen ingestion without prior liver disease. She is obtunded, localizing only to painful stimuli (Grade III encephalopathy). Vital signs: BP 96/54 mmHg, HR 112 bpm, RR 22 bpm, SpO2 96% on room air. Labs: AST 12,400 U/L, ALT 14,800 U/L, total bilirubin 6.8 mg/dL, INR 4.8, arterial pH 7.24, lactate 4.2 mmol/L, Cr 2.8 mg/dL, and ammonia 192 µmol/L.

Acute Liver Failure (ALF): Definition & Classification

Acute Liver Failure (ALF) is defined by the sudden onset of severe liver injury characterized by:

1. Coagulopathy: International Normalized Ratio (INR) >= 1.5.
2. Hepatic Encephalopathy: Any degree of altered mental status.
3. Absence of Preexisting Cirrhosis: Illness duration < 26 weeks.

Classification by Onset Timeline

• Hyperacute (< 7 days): Typically acetaminophen toxicity, ischemic hepatitis ("shock liver"), or hepatitis A/E. Marked by transaminases > 10,000 U/L, severe coagulopathy, high cerebral edema risk, and favorable transplant-free survival with N-acetylcysteine (NAC).
• Acute (7–21 days): Frequently viral hepatitis B or idiosyncratic drug-induced liver injury (DILI).
• Subacute (4–26 weeks): Typically non-acetaminophen DILI or autoimmune hepatitis. Features severe jaundice, mild transaminase elevation, lower cerebral edema risk, but poor transplant-free survival.

King's College Criteria for Emergent Transplantation

The King's College Criteria identify patients requiring super-urgent listing for orthotopic liver transplantation:

Intracranial Hypertension & Cerebral Edema in ALF

Cerebral edema affects up to 80% of patients with Grade IV encephalopathy and is the leading cause of death in ALF:

• Pathophysiology: Elevated circulating ammonia enters astrocytes where glutamine synthetase forms glutamine. Glutamine accumulation exerts an osmotic force, producing cytotoxic swelling, loss of autoregulation, and intracranial hypertension.
• Neurological Protection:
  • Grade III/IV encephalopathy mandates immediate endotracheal intubation. Target PaCO2 35–40 mmHg; avoid prolonged hyperventilation.
  • Elevate head of bed 30 degrees, maintain neutral head and neck positioning, minimize tracheal suctioning, and administer propofol sedation.
• Osmotherapy & Hemodynamics:
  • Target intracranial pressure (ICP) < 20 mmHg and cerebral perfusion pressure (CPP = MAP - ICP) 60–80 mmHg.
  • Hypertonic Saline (3% NaCl): Continuous infusion targeting serum sodium 145–150 mEq/L to draw water out of swollen astrocytic tissue.
  • Mannitol (20%): Administer 0.5–1.0 g/kg IV bolus for acute ICP surges (provided serum osmolality < 320 mOsm/kg and normal renal function).
  • Avoid hypotonic IV crystalloids (0.45% NaCl, D5W). Initiate continuous renal replacement therapy (CRRT) for ammonia > 150 µmol/L or severe acidosis.

Hepatic Encephalopathy in Cirrhosis

Pharmacotherapy & Precipitant Reversal

• Lactulose: First-line. Administer 20–30 g (30–45 mL) PO/NG q1–2h until bowel movement, then titrate to 2 to 3 soft bowel movements per day (or retention enema: 300 mL lactulose in 700 mL water). Fermentation into organic acids lowers colonic pH (< 5.0), converting diffusible NH3 into non-absorbable NH4⁺ ("ion trapping") for fecal excretion.
• Rifaximin: 550 mg PO BID added to lactulose to eliminate ammonia-producing enteric flora.
• Identify Precipitants: 90% of episodes have triggers: infection (SBP, UTI), GI hemorrhage (protein load), hypokalemic metabolic alkalosis (promotes renal ammonia synthesis and conversion to NH3), constipation, dehydration, or sedatives.

Spontaneous Bacterial Peritonitis (SBP)

• Diagnostic Paracentesis: Mandatory in any cirrhotic patient admitted with ascites, encephalopathy, fever, abdominal pain, or worsening renal/hepatic function.
• Diagnostic Criteria: Ascitic fluid absolute polymorphonuclear (PMN) count >= 250 cells/mm³ (total WBC x % neutrophils).
• Antibiotics: Initiate ceftriaxone 2 g IV q24h immediately post-paracentesis.
• Intravenous Albumin: Administer 1.5 g/kg IV within 6 hours of diagnosis on Day 1, followed by 1.0 g/kg IV on Day 3. Albumin expands arterial volume, reducing hepatorenal syndrome incidence from 30% to 10% and decreasing mortality.

Hepatorenal Syndrome (HRS-AKI)

An AKI phenotype driven by advanced cirrhotic circulatory dysfunction and renal vasoconstriction; it can coexist with tubular injury or chronic kidney disease:

• Current ADQI/ICA Criteria: Cirrhosis with ascites; AKI (creatinine rise≥0.3 mg/dL within 48 hours or≥50% within 7 days, and/or urine output≤0.5 mL/kg/hr for≥6 hours); no improvement within 24 hours after adequate volume resuscitation when clinically indicated; and no strong evidence of another primary cause. Investigate infection, shock, nephrotoxins, obstruction and structural injury. HRS can coexist with proteinuria, tubular injury or CKD. Do not require routine 48-hour albumin loading in a euvolemic or overloaded patient.
• Medical Management: Start terlipressin with 20–25% albumin promptly after diagnosis; norepinephrine is an ICU alternative when terlipressin is unavailable or contraindicated. US terlipressin starts at 0.85 mg IV every 6 hours with response-based adjustment. Reassess albumin daily (often 20–40 g/day) and stop it for overload/pulmonary edema. Check oxygenation before terlipressin, do not initiate during hypoxia, and monitor continuously; discontinue if SpO2 falls below 90%. Transplant evaluation proceeds concurrently; liver transplantation is definitive treatment.