Acute Liver Failure

GI NOTES

Acute Liver Failure

Key points

Acute liver failure (ALF) is severe liver injury with coagulopathy (INR 1.5 or more) and encephalopathy, in a patient without known cirrhosis, within 26 weeks of illness onset.
Acetaminophen is the leading cause in the United States and Europe.
Give N-acetylcysteine early for acetaminophen ALF, and consider it in non-acetaminophen ALF with early encephalopathy.
Contact a transplant center early; transfer before encephalopathy deepens.
Death is mainly from cerebral edema, infection and multiorgan failure; ICU care focuses on preventing these.

1. Causes and the work-up

Cause	Clues	Specific treatment
Acetaminophen	Very high ALT (often thousands), low bilirubin; level may be undetectable after staggered ingestion	N-acetylcysteine
Idiosyncratic drug injury	Antibiotics (amoxicillin-clavulanate, isoniazid), antiepileptics, herbal and dietary supplements	Stop the drug; NAC
Viral hepatitis	Hepatitis A, B (including reactivation), E (pregnancy), HSV, VZV	Tenofovir or entecavir for HBV; acyclovir for HSV
Autoimmune hepatitis	Raised IgG, autoantibodies (may be negative)	Corticosteroids in selected cases
Wilson disease	Young patient, hemolysis, low alkaline phosphatase, ALP-to-bilirubin ratio under 4	Urgent transplant evaluation
Ischemic hepatitis	Shock or heart failure; very high ALT that falls quickly	Restore circulation
Budd-Chiari syndrome	Ascites, hepatomegaly, abdominal pain	Anticoagulation, TIPS
Pregnancy-related	Acute fatty liver of pregnancy, HELLP	Prompt delivery
Mushroom (Amanita)	Severe diarrhea 6 to 24 hours after ingestion	NAC, silibinin where available

Initial labs: INR, liver panel, glucose, arterial lactate, ammonia, creatinine, phosphate, blood gas, acetaminophen level, toxicology, viral serologies, autoimmune markers, ceruloplasmin, pregnancy test, HIV.
Imaging: Doppler ultrasound for vessel patency and liver size.

2. First hours

FIGURE: ACUTE LIVER FAILURE PATHWAY

Acute liver injury with INR 1.5 or more and any confusion

Call a transplant center now

Start N-acetylcysteine; treat the cause

ICU: glucose, fluids, infection watch, airway if grade 3 or 4 encephalopathy

Reassess prognosis daily (King’s College criteria) for transplant listing

Original diagram based on the ACG 2023 acute liver failure guideline.

N-acetylcysteine (IV): a common 21-hour regimen is 150 mg/kg over 1 hour, 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours; in ALF it is often continued until INR improves. Check the local protocol.
Avoid sedatives where possible; do not routinely correct INR with plasma unless bleeding or before a procedure.
Check glucose often; hypoglycemia is common.

3. ICU care by organ system

Brain: intubate for grade 3 or 4 encephalopathy. Arterial ammonia above about 150 to 200 µmol/L predicts cerebral edema. Keep the head up 30°, sodium 145 to 155 mmol/L, avoid fever. For intracranial hypertension: hypertonic saline or mannitol, brief hyperventilation as a bridge.
Circulation: balanced crystalloids; norepinephrine for hypotension; consider hydrocortisone if refractory.
Kidneys: continuous renal replacement therapy (not intermittent) also lowers ammonia.
Infection: high risk; culture regularly and have a low threshold for antibiotics and antifungals.
Coagulation: INR is a prognostic marker; bleeding is uncommon. Give vitamin K once.
Nutrition: early enteral feeding with moderate protein.

4. King’s College criteria (listing for transplant)

Acetaminophen ALF	Non-acetaminophen ALF
Arterial pH under 7.30 after fluid resuscitation or all three: INR above 6.5, creatinine above 3.4 mg/dL, grade 3 or 4 encephalopathy	INR above 6.5 or any three: age under 10 or over 40; unfavorable cause (drug injury, Wilson, indeterminate); jaundice more than 7 days before encephalopathy; INR above 3.5; bilirubin above 17.5 mg/dL

Arterial lactate above 3.5 mmol/L at 4 hours (or above 3.0 after fluids) adds prognostic value in acetaminophen ALF. Meeting the criteria predicts poor survival without transplant; not meeting them does not guarantee survival.

Self-check questions

What three elements define acute liver failure?
Should NAC be given if the acetaminophen level is undetectable?
A 20-year-old with ALF has hemolysis and a very low alkaline phosphatase. What diagnosis, and what is the treatment?
Which kidney replacement method is preferred?

Answers: (1) INR 1.5 or more, encephalopathy, no prior cirrhosis (illness under 26 weeks). (2) Yes; NAC is given in ALF regardless of the level, and it helps non-acetaminophen ALF with early encephalopathy. (3) Acute Wilson disease; urgent transplant evaluation. (4) Continuous renal replacement therapy.

References

Shingina A, Mukhtar N, Wakim-Fleming J, et al. Acute Liver Failure Guidelines. Am J Gastroenterol. 2023;118(7):1128-1153.
Wendon J, Cordoba J, Dhawan A, et al. EASL Clinical Practical Guidelines on the management of acute (fulminant) liver failure. J Hepatol. 2017;66(5):1047-1081.
Lee WM, Hynan LS, Rossaro L, et al. Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure. Gastroenterology. 2009;137(3):856-864.
O’Grady JG, Alexander GJ, Hayllar KM, Williams R. Early indicators of prognosis in fulminant hepatic failure. Gastroenterology. 1989;97(2):439-445.

For educational purposes only. This note does not replace clinical judgment or local protocols. Check doses against current labeling and institutional guidance.