Suspected acute liver failure (adult)
INR 1.5 or more, any encephalopathy, no known cirrhosis, illness under 26 weeks. AIH, Wilson disease and Budd-Chiari can still count as ALF.
All Pathways
GastroenterologyEmergency
Acute Liver Failure in Adults (ACG 2023)
Acute Liver Failure in Adults (ACG 2023): Suspected acute liver failure (adult) → Not for children or cirrhosis: check first → Call the liver transplant...
Pathway Overview
17 steps
Algorithm Steps
17 total
01Start 02Warning Not for children or cirrhosis: check first
This pathway is for adults with ALF. Check these first.
- Child under 18 years: call the paediatric liver unit. Do not give NAC for non-paracetamol ALF in children.
- Known cirrhosis or chronic liver disease: this is ACLF or decompensated cirrhosis. Use that pathway.
- Pregnant: obstetric emergency. AFLP or HELLP needs urgent delivery.
03Action Call the liver transplant unit now; ICU care
Every patient with ALF: discuss with the state liver transplant unit on day 1. Patients can worsen within hours.
- Call the liver transplant unit now and plan early transfer
- ICU from grade 2 encephalopathy; neuro checks every 1-2 h
- Glucose every 1-2 h; give 10% glucose infusion if low
- Stop all non-essential drugs; avoid sedatives, opioids and metoclopramide
- Avoid hypotonic IV fluids (hyponatraemia worsens cerebral oedema)
- Arterial line; central line in ICU
04Action Find the cause now
The cause changes treatment and prognosis. Send all tests on admission.
- Paracetamol level and ALT, even if more than 24 h or level undetectable
- HSV PCR (VZV PCR if rash); HAV IgM; HBsAg, anti-HBc IgM, HBV DNA; HEV IgM or PCR
- Pregnancy test in all women of childbearing age
- ANA, anti-smooth muscle antibody, IgG (autoimmune hepatitis)
- Caeruloplasmin, serum and urine copper; Coombs-negative haemolysis, low ALP (Wilson disease)
- Drug, supplement, herbal, alcohol and mushroom history; urine and serum toxicology
- Doppler ultrasound liver: Budd-Chiari, malignant infiltration, chronic liver disease
- Arterial blood gas, lactate, ammonia, lipase, blood cultures; blood group (ABO, Rh) and HIV serology for transplant work-up
05Action Start cause-specific treatment now
Do not wait for all results. Paracetamol possible or cause unknown: give NAC (next step).
- HSV or VZV suspected: IV aciclovir 10 mg/kg every 8 h now, before the PCR result (adult; ideal body weight if obese). CrCl 25-50 mL/min: every 12 h; 10-25: every 24 h; below 10: 5 mg/kg every 24 h
- Pregnancy with AFLP or HELLP: urgent delivery with obstetrics
- Hepatitis B (acute or reactivation): start entecavir or tenofovir
- Amanita mushrooms: Poisons Information Centre 13 11 26; IV silibinin (IV benzylpenicillin if not available); refer for transplant early
- Autoimmune hepatitis: corticosteroids on liver unit advice; do not delay transplant assessment
- Budd-Chiari: IV heparin unless active bleeding; TIPS if no response
- Wilson disease: refer for transplant now (chelators do not work in ALF)
- Drug-induced: stop the drug. Malignant infiltration: oncology (transplant not an option)
06Decision Give IV NAC?
Yes: any possible paracetamol cause (even late, or level undetectable), or adult non-paracetamol ALF with grade 1-2 HE. If unsure about paracetamol, give NAC.
- If Yes
- Give NAC
07Action Yes: IV NAC, adult two-bag regimen
Start as soon as ALF is suspected. Paracetamol ALF: all patients. Non-paracetamol ALF: adults with grade 1-2 HE.
- Bag 1: 200 mg/kg (max 22 g) IV over 4 h in 500 mL glucose 5% or sodium chloride 0.9%
- Bag 2: 100 mg/kg (max 11 g) IV over 16 h in 1000 mL glucose 5% or sodium chloride 0.9%
- Then continue at the bag 2 rate (100 mg/kg, max 11 g, per 16 h)
- Paracetamol ALF: continue until INR below 2, ALT falling and patient clinically well, or transplant
- Non-paracetamol ALF: 72 h in total (trial regimen)
08Decision Grade 3-4 hepatic encephalopathy?
West Haven grade. Grade 3: somnolent but rousable, marked confusion. Grade 4: coma. Reassess every 1-2 h.
- Grade 1: mild confusion, altered sleep
- Grade 2: lethargy, disorientation, asterixis
- Grade 3: somnolent but rousable, marked confusion
- Grade 4: coma
- If Yes
- Grade 3-4
09Warning Yes: grade 3-4 HE: intubate; high risk of cerebral oedema
ICP monitor only in expert centres. Low sodium: raise it by no more than 6-8 mmol/L in 24 h. Refractory raised ICP: liver ICU specialist care.
- Intubate for airway protection, then sedate; head up 30 degrees
- Prevent raised ICP: avoid hyponatraemia, fever and low glucose; early CRRT for high ammonia
- Raised ICP: mannitol 0.5-1 g/kg IV (20% = 2.5-5 mL/kg; not if anuric) or 3% saline 250-500 mL; keep Na below 160 mmol/L
10Action Organ support for all patients
Septic-shock-like physiology. Do not correct INR unless bleeding or before a high-risk procedure.
- Hypotension: IV fluid, then noradrenaline; add vasopressin if no response. Aim for a MAP that keeps CPP 60-80 mmHg
- No FFP, platelets or clotting factors unless bleeding or before a high-risk procedure
- AKI, acidosis, fluid overload or high ammonia: early CRRT (not intermittent dialysis)
- Keep glucose about 6-10 mmol/L; 10-20% glucose infusion if needed
- Cultures on admission and if worse; no routine prophylactic antibiotics; start empirical antibiotics if deteriorating
- PPI stress-ulcer prophylaxis; avoid nephrotoxic drugs
- Enteral nutrition if no oral intake within 5-7 days
11Decision Poor-prognosis criteria met?
Check King's College criteria or MELD over 25 on admission, at least daily and at any deterioration. The liver transplant unit decides on listing.
- Paracetamol: arterial pH below 7.30 after fluid resuscitation
- Paracetamol: or all 3 of INR above 6.5, creatinine above 300 micromol/L, grade 3-4 HE
- Paracetamol: or lactate above 3.5 mmol/L at 4 h, or above 3.0 mmol/L after fluid resuscitation
- Non-paracetamol: INR above 6.5, or any 3 of: age above 40 years; non-A non-B hepatitis or drug reaction; jaundice more than 7 days before HE; INR above 3.5; bilirubin above 300 micromol/L
- Any cause: MELD above 25
- Wilson disease ALF, or pregnancy-related ALF not improving after delivery: refer for transplant
- If Yes
- Poor prognosis
12Action Yes: urgent listing for liver transplant
Poor prognosis without transplant. Transfer to the transplant centre now if not already there.
- Urgent listing through the liver transplant unit. AU/NZ: TSANZ Category 1 if ventilated in ICU, 2a if not yet ventilated and King's criteria met. US: UNOS status 1A
- Continue organ support, NAC and cause-specific treatment
- Brain death is the only absolute contraindication; sepsis, multiorgan failure and cancer are relative
- High-volume plasma exchange: specialist-centre bridge option; INR is then not valid for prognosis
13Outcome Liver transplantation
1-year survival after transplant for ALF is about 80%.
If No- Criteria not met
14Action No: criteria not met: continue care and reassess
ALF can change within hours. Stay in contact with the liver transplant unit.
- Reassess prognostic criteria at least daily and at any deterioration
- Continue organ support and NAC until stop criteria are met
- Watch for infection, AKI and rising grade of HE
15Outcome Recovery with medical care
Transplant-free survival is best in hyperacute causes: paracetamol, hepatitis A and E, and ischaemic injury.
- Reassess
- Path rejoins step 11Shared downstream outcome
If No- Grade 1-2
16Action No: grade 1-2 HE: close monitoring
ICU from grade 2. Any encephalopathy: transfer to a liver transplant centre.
- Neuro checks every 1-2 h; intubate if HE reaches grade 3
- Avoid sedatives and opioids
- Lactulose: no proven benefit in ALF; bowel gas can hinder transplant surgery. Never give lactulose enemas.
- Correct glucose, sodium, potassium, magnesium and phosphate
- Path rejoins step 10Shared downstream outcome
If No- No NAC
17Action No: adult non-paracetamol ALF, HE grade 3-4; or child, non-paracetamol ALF
Adults with non-paracetamol ALF and grade 3-4 HE: NAC showed no benefit; liver unit decides. Children with non-paracetamol ALF: do not give NAC (lower transplant-free survival in trial).
- Path rejoins step 08Shared downstream outcome
Guideline Source
ACG Clinical Guideline: Acute Liver Failure (Shingina et al., Am J Gastroenterol 2023;118:1128-1153)
Clinical Safety Information
Clinical Decision Support — Not a Substitute for Clinical Judgment
Individual patient factors may require deviation from these recommendations.
Known Limitations
- Adults only. Children: call the paediatric liver unit; do not give NAC for non-paracetamol ALF in children.
- King's College criteria and MELD have limited sensitivity; the liver transplant unit decides on listing.
- Evidence for most ALF treatments is low quality (few randomised trials).
- Doses of silibinin and penicillin for Amanita poisoning: get Poisons Information Centre advice.
Contraindicated Populations
Children under 18 years (use paediatric ALF guidance)Cirrhosis or acute-on-chronic liver failure (not ALF)
Applicable Regions
AUNZUSUKEU
EU: EASL 2017 ALF clinical practice guideline.
UK: UK revised emergency liver transplant selection criteria apply.
US: ACG 2023 guideline; urgent listing as UNOS status 1A.
AU/NZ: NAC two-bag regimen and stop criteria from the ANZ paracetamol guideline (Chiew 2020). Refer every ALF patient to the state liver transplant unit. Poisons Information Centre 13 11 26.
Version 2Next review: 2027-09-30
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Frequently Asked Questions
What is the Acute Liver Failure in Adults (ACG 2023)?
The Acute Liver Failure in Adults (ACG 2023) is a emergency clinical algorithm for Gastroenterology. It provides a structured decision tree to guide clinical decision-making, based on ACG Clinical Guideline: Acute Liver Failure (Shingina et al., Am J Gastroenterol 2023;118:1128-1153).
What guideline is the Acute Liver Failure in Adults (ACG 2023) based on?
This algorithm is based on ACG Clinical Guideline: Acute Liver Failure (Shingina et al., Am J Gastroenterol 2023;118:1128-1153) (DOI: 10.14309/ajg.0000000000002340).
What are the limitations of the Acute Liver Failure in Adults (ACG 2023)?
Known limitations include: Adults only. Children: call the paediatric liver unit; do not give NAC for non-paracetamol ALF in children.; King's College criteria and MELD have limited sensitivity; the liver transplant unit decides on listing.; Evidence for most ALF treatments is low quality (few randomised trials).; Doses of silibinin and penicillin for Amanita poisoning: get Poisons Information Centre advice.. Individual patient factors may require deviation from these recommendations.
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