Red Flags
- INR ≥1.5 + any-grade hepatic encephalopathy in a patient without pre-existing liver disease and illness <26 weeks — acute liver failure; transplant centre referral[1]
- Grade III–IV encephalopathy — ICU; intracranial hypertension risk; head-up positioning, mannitol or hypertonic saline if cerebral oedema[1]
- Paracetamol overdose with shock or rising ALT despite NAC — King's College criteria for transplant: pH <7.3 OR all of (PT >100s, creatinine >300, encephalopathy ≥III)[1]
- Pregnancy with ALF — exclude HELLP, AFLP, HEV (high mortality in pregnancy); urgent obstetric and hepatology coordination[1]
First-line treatment
Interventions
- Liver transplantation evaluation[1]All ALF patients should be discussed urgently with transplant centre; King's College criteria (paracetamol and non-paracetamol) and Clichy criteria guide listing
- Specific aetiology-targeted therapy[1]Paracetamol → NAC. HBV → tenofovir/entecavir. HSV → aciclovir. Autoimmune → corticosteroids (with caution). Wilson → chelation + transplant. Mushroom (Amanita) → silibinin + NAC + supportive
First-line drug therapy
| Drug | Class | Adult | Paediatric | Notes |
|---|---|---|---|---|
| N-acetylcysteine (NAC)[1] | Glutathione precursor | 150 mg/kg IV over 1 h, then 50 mg/kg over 4 h, then 100 mg/kg over 16 h (21-h regimen, may extend) | Same per kg | Paracetamol-induced ALF (definitive). Also used in non-paracetamol ALF (improves transplant-free survival per Lee 2009) |
| Lactulose plus rifaximin (ACLF encephalopathy) | Ammonia-lowering combination | For ACLF: lactulose 20–30 mL every 6 hours, titrated to 3–4 stools/day; rifaximin 400 mg three times daily. [2] | Per weight | Listed in the July 2020 ICMR STW for ACLF-associated encephalopathy; the same box does not establish this regimen for ALF. [2] |
| Hypertonic saline or mannitol (cerebral oedema)[1] | Osmotherapy | 3% saline to target Na 145–155 mmol/L; mannitol 0.5–1 g/kg IV bolus | — | Grade III–IV encephalopathy with cerebral oedema; consider ICP monitoring in selected cases |
| Glucose infusion (hypoglycaemia prevention)[1] | IV dextrose | 10% dextrose infusion to maintain glucose >70 mg/dL; serial glucose monitoring | — | Hypoglycaemia common in ALF due to depleted hepatic gluconeogenesis |
| Vitamin K[1] | Coagulation factor cofactor | 10 mg IV daily × 3 days | — | Correct any vitamin K deficiency contributing to coagulopathy; does NOT correct synthetic dysfunction in ALF |
N-acetylcysteine (NAC)[1]
Glutathione precursor
- Adult
- 150 mg/kg IV over 1 h, then 50 mg/kg over 4 h, then 100 mg/kg over 16 h (21-h regimen, may extend)
- Paediatric
- Same per kg
Paracetamol-induced ALF (definitive). Also used in non-paracetamol ALF (improves transplant-free survival per Lee 2009)
Lactulose plus rifaximin (ACLF encephalopathy)
Ammonia-lowering combination
- Adult
- For ACLF: lactulose 20–30 mL every 6 hours, titrated to 3–4 stools/day; rifaximin 400 mg three times daily. [2]
- Paediatric
- Per weight
Listed in the July 2020 ICMR STW for ACLF-associated encephalopathy; the same box does not establish this regimen for ALF. [2]
Hypertonic saline or mannitol (cerebral oedema)[1]
Osmotherapy
- Adult
- 3% saline to target Na 145–155 mmol/L; mannitol 0.5–1 g/kg IV bolus
- Paediatric
- —
Grade III–IV encephalopathy with cerebral oedema; consider ICP monitoring in selected cases
Glucose infusion (hypoglycaemia prevention)[1]
IV dextrose
- Adult
- 10% dextrose infusion to maintain glucose >70 mg/dL; serial glucose monitoring
- Paediatric
- —
Hypoglycaemia common in ALF due to depleted hepatic gluconeogenesis
Vitamin K[1]
Coagulation factor cofactor
- Adult
- 10 mg IV daily × 3 days
- Paediatric
- —
Correct any vitamin K deficiency contributing to coagulopathy; does NOT correct synthetic dysfunction in ALF
Safety-net
- Avoid all hepatotoxic medications and supplements; consult clinician before any new drug or herbal product[1]
- Worsening confusion, drowsiness, easy bruising, vomiting blood, or yellow eyes — call emergency services immediately[1]
- If you survive ALF and recover, avoid alcohol completely until cleared by hepatology[1]
Referral criteria
- Suspected ALF (INR ≥1.5 + encephalopathy without prior liver disease)Transplant centre / liver intensive care same-day[1]
- Paracetamol overdose meeting King's College criteriaLiver transplant centre[1]
- Pregnancy with ALFJoint hepatology + maternal-fetal medicine[1]
- Wilson's disease ALFTransplant centre — Wilson ALF rarely recovers without transplant[1]
Clinical summary
Recognition and management of acute liver failure — coagulopathy + encephalopathy in patients without prior liver disease; transplant evaluation is time-critical.