Acute Liver Failure (ALF)  

🔹 Definition

Acute Liver Failure (ALF) is a rapidly progressive hepatic dysfunction occurring in a patient without preexisting liver disease, characterized by:

• Acute onset (≤ 26 weeks) of liver injury,

• Coagulopathy (INR > 1.5), and

• Hepatic encephalopathy.

🧩 Subtypes (based on time from jaundice → encephalopathy):

Subtype	Interval	Typical Causes
Hyperacute	≤ 7 days	Acetaminophen toxicity, HAV, HEV, ischemic hepatitis
Acute	1–3 weeks	HBV, autoimmune hepatitis
Subacute	3–26 weeks	Wilson disease, drug-induced liver injury

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🔹 Related Terms

Term	Description
Acute liver injury	Elevated aminotransferases ± hyperbilirubinemia + coagulopathy but no encephalopathy
Acute-on-chronic liver failure (ACLF)	Acute deterioration of chronic liver disease → multiorgan failure and high short-term mortality

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🔹 Etiology

Category	Common Causes
1. Drug/Toxin-Induced (Most common in US)	Acetaminophen overdose (main cause), isoniazid, valproate, halothane, methyldopa, herbal supplements (kava, green tea extract)
2. Viral Infections	HAV, HBV, HEV, HBV-HDV coinfection; less common: HSV, CMV, EBV, adenovirus
3. Vascular Disorders	Budd–Chiari syndrome, ischemic hepatitis (“shock liver”)
4. Pregnancy-Related	HELLP syndrome, acute fatty liver of pregnancy
5. Metabolic / Genetic	Wilson disease, Reye syndrome
6. Autoimmune	Autoimmune hepatitis
7. Others	Toxins (e.g., Amanita phalloides mushroom), malignancy (e.g., lymphoma, metastatic cancer)
8. Idiopathic	20–45% of cases

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🔹 Pathophysiology

• Massive hepatocellular necrosis → ↓ detoxification, ↓ protein synthesis, ↑ ammonia.

• Loss of synthetic function → coagulopathy (↑ INR), hypoglycemia, hypoalbuminemia.

• Accumulation of neurotoxins (esp. ammonia) → cerebral edema and encephalopathy.

• Systemic inflammation → multiorgan failure (renal, circulatory, respiratory).

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🔹 Clinical Features

System	Findings
General	Nausea, vomiting, malaise, fatigue, anorexia
Skin	Jaundice, pruritus
Neurologic (encephalopathy)	Confusion, asterixis, altered LOC, seizures, coma
Abdomen	RUQ pain, tenderness, distension, ascites
Other	Signs of cerebral edema (papilledema, hypertension, bradycardia), fetor hepaticus
Specific clues	Kayser–Fleischer rings → Wilson disease; rash → HSV/viral

⚠️ In hyperacute ALF, encephalopathy may dominate with minimal jaundice.

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🔹 Differential Diagnosis

• Decompensated cirrhosis

• Severe acute hepatitis (without encephalopathy)

• Sepsis with encephalopathy

• Hypoxic/ischemic liver injury

• Metabolic/toxic encephalopathy (uremia, hypoglycemia)

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🔹 Diagnostic Criteria

ALF is confirmed when:

1. Hepatic encephalopathy, AND

2. Coagulopathy (INR ≥ 1.5), AND

3. No prior chronic liver disease

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🔹 Investigations

1. Basic Laboratory Workup

Test	Findings
Liver panel	↑ ALT, AST (often >1000 in acetaminophen or ischemic injury), ↑ bilirubin
Coagulation	↑ INR (>1.5), prolonged PT, variable fibrinogen
Renal panel	↑ creatinine, BUN (hepatorenal syndrome)
Electrolytes	Hyponatremia, hypokalemia, hypophosphatemia
Glucose	Hypoglycemia (↓ gluconeogenesis)
CBC	Thrombocytopenia, possible leukocytosis
Ammonia	Elevated (>150 µmol/L = ↑ risk of cerebral edema)
LDH, lactate	Elevated, correlate with tissue necrosis and severity

2. Etiologic Testing

• Viral hepatitis panel (HAV, HBV, HCV, HEV, HSV, CMV, EBV)

• Serum acetaminophen level

• Urine toxicology screen

• Autoimmune markers (ANA, SMA, IgG)

• Ceruloplasmin, 24h urinary copper (Wilson disease)

• Pregnancy test (HELLP, AFLP)

• α-fetoprotein (hepatoma)

• Blood/urine cultures (rule out infection)

3. Imaging

• Abdominal ultrasound with Doppler: assess flow, detect Budd–Chiari, ischemia, ascites.

• CT/MRI brain: rule out other causes of altered mental status; detect cerebral edema.

Liver biopsy only if diagnosis unclear and will change management — bleeding risk is high.

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🔹 Management Overview

A. Stabilization

• ICU admission immediately.

• Airway protection: Early intubation if grade ≥ 3 encephalopathy.

• Circulation: IV fluids (normal saline); maintain MAP 60–80 mmHg.

  • If persistent hypotension → norepinephrine ± vasopressin.

  • Add hydrocortisone for refractory shock.

• Monitor: BP, SpO₂, urine output, glucose, ICP (if transplant candidate).

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B. Specific Therapy

Etiology	Specific Treatment
Acetaminophen toxicity	IV or PO N-acetylcysteine (NAC) ASAP (even if uncertain).
Viral hepatitis (HBV, HSV)	Start antivirals.
Autoimmune hepatitis	High-dose corticosteroids.
Amanita phalloides	Silibinin (preferred) or penicillin G + NAC.
Wilson disease	Chelation (trientine, D-penicillamine) if stable; transplant if severe.
Pregnancy-related ALF	Urgent delivery of fetus.

NAC is also beneficial in non-acetaminophen ALF (improves transplant-free survival).

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C. Control of Complications

1. Cerebral Edema & ICP

• Head elevation 30°

• Avoid hyponatremia; maintain Na⁺ > 145 mmol/L

• Mannitol 0.25–1 g/kg IV or hypertonic saline

• Controlled hyperventilation (temporary)

• Avoid sedatives if possible

• Early CRRT (reduces ammonia)

2. Encephalopathy

• Lactulose 30–60 mL every 2–6h (if not intubated)

• Rifaximin (adjunct, benefit uncertain)

3. Coagulopathy

• Replace only if bleeding or before invasive procedure:

  • FFP, cryoprecipitate (if fibrinogen <100 mg/dL), vitamin K, platelets.

• Avoid prophylactic correction unless indicated.

4. Hypoglycemia

• Continuous glucose infusion to maintain 100–150 mg/dL.

5. AKI / Hepatorenal Syndrome

• Optimize perfusion; early CRRT preferred.

6. Infection

• Frequent monitoring; empiric antibiotics if sepsis suspected.

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D. Liver Transplantation

Definitive therapy for most ALF cases.

Assess early using King’s College Criteria:

Etiology	Criteria for Transplant
Acetaminophen	pH < 7.3 (after fluid resuscitation) OR all 3: – INR > 6.5 – Creatinine > 3.4 mg/dL – Grade III–IV encephalopathy
Other causes	INR > 6.5 OR ≥ 3 of: – Age <10 or >40 – Jaundice >7 days before encephalopathy – INR >3.5 – Bilirubin >17.5 mg/dL – Unfavorable cause (e.g., drug-induced, indeterminate)

MELD score (>30 = poor prognosis) can also help prioritize candidates.

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🔹 Prognosis

Factor	Impact
Overall mortality	30–40% (without transplant)
Better prognosis	Acetaminophen toxicity, HAV, pregnancy-related, ischemic injury
Worse prognosis	Indeterminate cause, Wilson disease, idiosyncratic DILI, autoimmune
Post-transplant survival	65–85% at 1 year

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🧠 Key Takeaways

• Always suspect ALF in any acutely ill, jaundiced patient with confusion and coagulopathy.

• Act fast: diagnosis and referral to a liver transplant center saves lives.

• NAC is safe, cheap, and beneficial—start immediately if in doubt.

• Cerebral edema and sepsis are leading causes of death.