Conditions · Gastroenterology and hepatology
Acute liver failure !
A sudden, severe loss of liver function in a person without previous liver disease, causing bleeding problems and confusion. It is an emergency.
Updated 2026-11-01
Structures involved
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Why it happens
- Patterns of necrosis: coagulative, liquefactive, caseous, fat, fibrinoid, gangrenous
- Chemical (toxic) cell injury: direct and after metabolism
- Liver regeneration
- Watershed areas and the organs most sensitive to ischemia
- Reversible vs irreversible cell injury: the point of no return
- Functions of the liver
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What it is
Rapid severe liver injury with coagulopathy (INR of 1.5 or more) and hepatic encephalopathy in a person without pre-existing cirrhosis, developing within 26 weeks of the first symptoms.
Who gets it
Rare but highly lethal. Paracetamol (acetaminophen) overdose dominates in the United States and the United Kingdom, while viral hepatitis (A, B, E) is a leading cause in many developing regions; in Colombia hepatitis A in children and young adults, hepatitis B and drug-induced injury are important, and dengue, leptospirosis and yellow fever can cause severe hepatitis.
Causes
- Paracetamol (acetaminophen) overdose, intentional or accidental
- Viral hepatitis A, B (with or without D) and E; herpes viruses in immunosuppressed people
- Idiosyncratic drug-induced liver injury (some antibiotics, antituberculosis drugs, antiepileptics) and herbal supplements
- Autoimmune hepatitis and Wilson disease
- Ischaemic hepatitis (shock), Budd-Chiari syndrome
- Pregnancy-related: acute fatty liver of pregnancy and HELLP syndrome
- Mushroom poisoning (Amanita) and other toxins
Risk factors
- Chronic alcohol use or fasting, which increase paracetamol toxicity
- Lack of hepatitis A or B vaccination
- Use of hepatotoxic drugs or supplements
- Pregnancy in the third trimester (pregnancy-related causes)
Pathophysiology
Massive hepatocyte necrosis or apoptosis abruptly removes the liver's synthetic, metabolic and detoxifying functions. Clotting factor production falls (high INR), glucose output fails (hypoglycaemia) and ammonia rises, causing encephalopathy and astrocyte swelling that can lead to cerebral oedema and herniation. A systemic inflammatory response causes vasodilation, multi-organ failure and susceptibility to infection.
Classification
- Hyperacute: encephalopathy within 7 days of jaundice (typical of paracetamol); highest cerebral oedema risk but better spontaneous survival
- Acute: 8 to 28 days
- Subacute: 4 to 26 weeks; lower cerebral oedema risk but poorer spontaneous survival
Symptoms and signs
- Nausea, vomiting, malaise and right upper quadrant pain
- Jaundice
- Confusion, drowsiness or agitation (encephalopathy)
- Easy bruising or bleeding
- Reduced urine output
Diagnosis
- Clinical
- Acute hepatitis with encephalopathy and coagulopathy and no prior cirrhosis. Careful history of drugs, supplements, paracetamol, travel, mushrooms, pregnancy and risk behaviours; serial neurological assessment.
- Tests
- INR, very high aminotransferases, bilirubin, glucose, arterial ammonia, lactate, creatinine, blood gas, phosphate, blood count; paracetamol level, toxicology screen, hepatitis A, B and E serology, autoimmune markers, ceruloplasmin and pregnancy test.
- Imaging
- Abdominal Doppler ultrasound to exclude Budd-Chiari syndrome and assess liver size; head CT when neurological status changes.
Differential diagnosis
- Decompensated chronic liver disease (acute-on-chronic liver failure)
- Sepsis with cholestasis and coagulopathy
- Severe alcohol-associated hepatitis
- HELLP syndrome without liver failure
- Disseminated intravascular coagulation
Goal of treatment
Treat the specific cause early, support failing organs in intensive care, prevent and manage cerebral oedema, and refer promptly to a transplant centre.
Treatment
- Acute
- N-acetylcysteine for paracetamol toxicity, and often in early non-paracetamol acute liver failure; cause-specific therapy such as antivirals for hepatitis B or urgent delivery in pregnancy-related causes.
- Acute
- Intensive care support: glucose infusion for hypoglycaemia, fluids and vasopressors, airway protection, renal replacement therapy, and blood products only for bleeding or procedures.
- Medical
- Measures against cerebral oedema: head elevation, avoiding stimulation, hyperosmolar therapy (hypertonic saline or mannitol) and control of fever.
- Follow-up
- Nursing care: hourly neurological checks, glucose monitoring, bleeding precautions, strict fluid balance and infection control.
- Surgical
- Emergency liver transplantation for patients who meet poor-prognosis criteria (such as the King's College criteria).
Complications
- Cerebral oedema and brain herniation
- Bacterial and fungal infections, sepsis
- Acute kidney injury
- Bleeding from coagulopathy
- Hypoglycaemia, hypophosphataemia and lactic acidosis
- Multi-organ failure
Prognosis
Outcome depends on the cause and speed of onset: paracetamol, hepatitis A and pregnancy-related causes have better spontaneous survival, whereas idiosyncratic drug injury and indeterminate cases often need transplantation. Without transplantation, mortality is high when poor-prognosis criteria are met.
Prevention
- Hepatitis A and B vaccination
- Safe use and storage of paracetamol and avoiding duplicate products
- Avoiding wild mushrooms and unregulated supplements
Test yourself
Think of the answer, then tap the question to see it.
What three features define acute liver failure?
Coagulopathy (INR of 1.5 or more), hepatic encephalopathy and no pre-existing cirrhosis, within 26 weeks of illness onset.
What is the antidote for paracetamol (acetaminophen) toxicity?
N-acetylcysteine, which restores glutathione; it works best when given early.
What is the most feared cause of death in hyperacute liver failure?
Cerebral oedema with raised intracranial pressure and brain herniation.
Which prognostic tool helps select patients for urgent transplantation?
The King's College criteria, which differ for paracetamol and non-paracetamol causes.
What metabolic complication requires frequent bedside checks?
Hypoglycaemia, because the failing liver cannot release glucose.
Related conditions
- Acetaminophen toxicity
- Viral hepatitis
- Wilson disease
- Hepatic encephalopathy
- Acute kidney injury
- Sepsis and septic shock
- Dengue
- Leptospirosis
- Cirrhosis
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Introduction to the Revised American Association for the Study of Liver Diseases Position Paper on Acute Liver Failure 2011 (Hepatology, 2012); Acetaminophen overdose: MedlinePlus Medical Encyclopedia (MedlinePlus (U.S. National Library of Medicine), 2025).
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