Acute liver failure

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 + rifaximin (encephalopathy)^[1]	Ammonia-lowering combination	Lactulose 30–45 mL PO/NG TDS titrated to 2–3 soft stools/day; rifaximin 550 mg PO BD	Per weight	Hepatic encephalopathy in ALF; rifaximin reduces recurrence
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 + rifaximin (encephalopathy)^[1]

Ammonia-lowering combination

Adult: Lactulose 30–45 mL PO/NG TDS titrated to 2–3 soft stools/day; rifaximin 550 mg PO BD
Paediatric: Per weight

Hepatic encephalopathy in ALF; rifaximin reduces recurrence

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.

References

1.AASLD Practice Guidance: Management of Acute Liver Failure (2023); ICMR Standard Treatment Workflow — Liver Failure (2023)