Acute Liver Failure (ALF)

 I. AASLD definition Definition

Acute Liver Failure (ALF) is defined as the rapid deterioration of liver function in a patient without pre-existing liver disease, characterized by:

• Hepatic encephalopathy, and
• Coagulopathy (INR ≥1.5),
• Within 26 weeks of the onset of symptoms.

 II. Etiology

🔸 A. Drug-induced (most common in Western countries)

🔸 B. Viral hepatitis (common in developing countries)

• Hepatitis A, B, E (especially in pregnancy)
• Herpes simplex, CMV, EBV

🔸 C. Other Causes

 III. Classification

• Hyperacute ALF: Higher ICP, better transplant-free survival
• Subacute ALF: Lower ICP, poorer outcomes

 IV. Pathophysiology

🔸 1. Massive hepatocellular necrosis → ↓ synthetic and detoxifying capacity

🔸 2. Hyperbilirubinemia, coagulopathy, hypoglycemia, lactic acidosis

🔸 3. Ammonia accumulation → cerebral edema

🔸 4. SIRS and immune dysregulation → sepsis-like syndrome

🔸 5. Multiorgan failure in late stages

 V. Clinical Features

 VI. Diagnosis

🔸 1. Liver function tests (LFTs)

• AST, ALT: Very high (>1000 IU/L) in ischemia, paracetamol
• Bilirubin: Elevated (total/direct)

🔸 2. Coagulation profile

• INR ≥ 1.5 (diagnostic criteria)
• PT: prolonged

🔸 3. Ammonia levels

• Correlate with risk of encephalopathy/cerebral edema

🔸 4. Viral serology (HAV, HBV, HCV, HEV, HSV, CMV)

🔸 5. Autoimmune markers

• ANA, SMA, LKM-1

🔸 6. Ceruloplasmin, 24-hr urinary copper: to rule out Wilson’s

🔸 7. Toxicology screen

• Paracetamol, salicylates, alcohol

🔸 8. Imaging

• CT/MRI: rule out ICH or space-occupying lesions (if encephalopathy)

 VII. Prognostic Scoring

🔸 1. King’s College Criteria

For Paracetamol-induced ALF:

• pH < 7.3 after resuscitation
  OR
• PT > 100 sec (INR >6.5), creatinine > 3.4 mg/dL, Grade III–IV HE

For Non-paracetamol ALF:

• PT > 100 sec (INR >6.5)
  OR
• Any 3 of:
• Age <10 or >40
• Jaundice to encephalopathy >7 days
• INR >3.5
• Bilirubin >17.6
• Drug-induced or non-A/non-B hepatitis

🔸 2. Model for End-Stage Liver Disease (MELD)

 VIII. Management

 Requires ICU admission in most cases

🔸 A. Airway and CNS management

Avoid steroids (not useful)

• ICP monitoring controversial (bleeding risk)

🔸 B. Hemodynamic Support

• Avoid overzealous fluid resuscitation
• Norepinephrine for vasopressor support
• Albumin in fluid resuscitation (oncotic support)

🔸 C. Renal Support

• Prevent and treat Hepatorenal Syndrome
• CRRT preferred in hemodynamically unstable

🔸 D. Coagulation

• INR correction only if bleeding or invasive procedure
• Platelets > 50,000/µL before invasive procedures
• FFP, cryoprecipitate (fibrinogen >100 mg/dL)
• Vitamin K

🔸 E. Infection Control

ALF = immunocompromised state.

Up to 80% develop infection.

Common:

• Pneumonia
• UTI
• Line sepsis

Strategy:

• Low threshold for cultures
• Daily surveillance
• Empiric broad-spectrum antibiotics if unstable
• Antifungal if prolonged ICU stay

⚠ Infection worsens encephalopathy.

 Should We Give Prophylactic Antibiotics?

Controversial.

Current Approach:

• NOT routinely recommended for all stable ALF patients
• BUT low threshold to start empiric antibiotics if:
• Grade III/IV encephalopathy
• On ventilator
• On vasopressors
• Awaiting transplant

Common empiric choices:

• Piperacillin-tazobactam
• Meropenem (if high risk)

Antifungal:

• Consider if ICU >5 days or high risk

🔸 F. Glucose Management

• Avoid hypoglycemia: 10% dextrose infusion

🔸 G. Nutritional Support

Goals

• Prevent catabolism
• Reduce ammonia production
• Maintain gut integrity

Energy Requirement

25–30 kcal/kg/day

Protein

OLD CONCEPT ❌: Restrict protein
NEW GUIDELINE ✔:

• 1.2–1.5 g/kg/day
• Avoid prolonged protein restriction
• Vegetable protein preferred
• BCAA may help in encephalopathy

Route

✔ Enteral preferred
✔ Start within 24 hours if stable

Avoid prolonged fasting → worsens muscle breakdown → ↑ ammonia

Glucose

• Continuous dextrose infusion
• Hourly monitoring
• Hypoglycemia common due to glycogen depletion

N-ACETYLCYSTEINE (NAC)

In Paracetamol toxicity

Mechanism:

• Replenishes glutathione
• Enhances NAPQI detoxification
• Improves microcirculation

 Extended Infusion Strategy (ICU Practice)

Continue NAC if:

• ALT rising
• INR worsening
• Detectable paracetamol level
• Ongoing liver failure

NON-Paracetamol ALF

Evidence supports:

• Improved transplant-free survival
• Better oxygen delivery
• Reduced oxidative stress

👉 Current guidelines: Start NAC in all ALF unless contraindicated

 AMMONIA CONTROL

Ammonia is central in cerebral edema.

Strategies:

• Lactulose (if not intubated)
• Rifaximin
• CRRT (effective removal)
• Avoid constipation

Ammonia >150–200 µmol/L → high cerebral edema risk

IX. Liver Transplantation

Indications:

• Fulfillment of King’s College Criteria
• Persistent encephalopathy or coagulopathy
• Rising bilirubin/INR despite supportive care

 Only definitive treatment in many cases