Gastrointestinal & Hepatic · Topic 4 of 26
Acute Liver Failure
Gastrointestinal · liver failure
Acute Liver Failure
INR 1.5 or more plus any encephalopathy in a previously healthy liver: give NAC, protect the brain, and call the transplant center early.
Key numbers
INR 1.5 or more plus encephalopathyINR ≥ 1.5 + HE
Grade 2 HE: ICU; grade 3–4: intubateHE grade ≥ 2 → ICU
IV NAC: 150 mg/kg over 1 hour first150 mg/kg over 1 h
King's College criteria or MELD over 25MELD > 25
01 · Defined byINR 1.5 or more plus encephalopathy
Acute liver failure = coagulopathy (INR ≥ 1.5) plus any degree of encephalopathy, illness under 26 weeks, no pre-existing liver disease — except Wilson disease, autoimmune hepatitis or Budd-Chiari presenting acutely.
02 · GiveGive N-acetylcysteine early
Acetaminophen is the leading US cause of ALF. Give N-acetylcysteine early whenever acetaminophen toxicity is suspected — even when ingestion time is unknown or late — without waiting for levels.
03 · FirstEncephalopathy: contact the transplant center now
Any encephalopathy in acute liver injury should trigger early transfer to, or discussion with, a liver transplant center; acetaminophen ALF can progress especially fast.
01
Diagnosis & monitoring
Work-upKing's College criteria or MELD over 25Prognosticate with King's College criteria or MELD: meeting KCC or MELD above 25 predicts poor outcome without transplant. KCC performs better in acetaminophen ALF, MELD in non-acetaminophen ALF.
King’s College criteria for acetaminophen ALFKing's College criteria for acetaminophen ALF: arterial pH below 7.3 after resuscitation, or all of INR above 6.5, creatinine above 3.4 mg/dL and grade 3–4 encephalopathy. Lactate and hypoglycemia add prognostic weight.
Check glucose often; infuse dextrose 10%Hypoglycemia is common and worsens encephalopathy: monitor closely, infuse dextrose 10% to keep glucose about 150–180 mg/dL, avoid hypotonic fluids, and replace magnesium and phosphorus every 8–12 hours as needed.
02
Do right now
In this orderFirst moves
1
→Give N-acetylcysteine early
2
→Encephalopathy: contact the transplant center now
3
→Grade 2 HE: ICU; grade 3–4: intubateHE grade ≥ 2 → ICU
4
Check glucose often; infuse dextrose 10%
Why each step
Give N-acetylcysteine earlyAcetaminophen is the leading US cause of ALF. Give N-acetylcysteine early whenever acetaminophen toxicity is suspected — even when ingestion time is unknown or late — without waiting for levels.
Encephalopathy: contact the transplant center nowAny encephalopathy in acute liver injury should trigger early transfer to, or discussion with, a liver transplant center; acetaminophen ALF can progress especially fast.
Grade 2 HE: ICU; grade 3–4: intubateMonitor patients with grade 2 or higher encephalopathy in an ICU, and intubate for airway protection at grade 3–4 encephalopathy.
Check glucose often; infuse dextrose 10%Hypoglycemia is common and worsens encephalopathy: monitor closely, infuse dextrose 10% to keep glucose about 150–180 mg/dL, avoid hypotonic fluids, and replace magnesium and phosphorus every 8–12 hours as needed.
03
Management
OrdersGive IV NAC in non-acetaminophen ALF too must knowGive IV N-acetylcysteine in non-acetaminophen ALF as well (ACG 2023 suggestion); its transplant-free survival benefit was shown in early (grade 1–2) encephalopathy.
IV NAC: 150 mg/kg over 1 hour firstIV N-acetylcysteine: 150 mg/kg over 1 hour, 50 mg/kg over 4 hours, 100 mg/kg over 16 hours (or 200 mg/kg over 4 hours, then 100 mg/kg over 16 hours); cap dosing weight at 100 kg.
Early CRRT for hyperammonemia with HEWith grade 2 or higher encephalopathy, start continuous renal replacement therapy early to clear ammonia even without standard dialysis indications; prefer CRRT over intermittent hemodialysis.
Raised ICP: hyperosmolar therapy, avoid hyponatremiaTreat intracranial hypertension with mannitol or hypertonic saline, hyperventilation and CRRT; avoid hyponatremia. Sodium is commonly kept at 145–150 mmol/L, and below 160 mmol/L with hypertonic saline.
Norepinephrine first; add vasopressinFor hypotension refractory to fluid resuscitation, norepinephrine is the first-line vasopressor; add vasopressin when norepinephrine alone is not enough.
HSV: empiric IV acyclovir; HBV: entecavir or tenofovirGive empiric IV acyclovir when ALF with features of HSV or zoster infection is suspected, pending PCR; treat hepatitis B reactivation with entecavir or tenofovir.
Pregnancy-related ALF: prompt deliveryHELLP syndrome or acute fatty liver of pregnancy causing ALF requires prompt delivery with multidisciplinary care; refer for transplant evaluation if the patient fails to improve after delivery.
04
Red flags & don'ts
Avoid harmDo not correct the INR routinely avoidDo not correct coagulopathy routinely without active bleeding or a planned high-risk procedure: the INR does not reflect bleeding risk in ALF; viscoelastic tests may assess it better.
No routine prophylactic antibiotics; culture often avoidDo not give routine prophylactic antimicrobials (no fall in bloodstream infection or 21-day mortality); obtain surveillance cultures, since infection is common and often silent, and treat empirically if the patient deteriorates.
05
Acetaminophen or non-acetaminophen ALF?
Commonly confused| Tempo | Hyperacute |
|---|---|
| Cerebral edema risk | Highest |
| Spontaneous survival | Best of the subtypes |
| N-acetylcysteine | Give early, even late or with unknown timing |
| Best prognostic score | King's College criteria |
06
More detail
ReferenceShow 6 reference facts
Etiology-specific care: IV silibinin for amatoxin mushroom poisoning (penicillin G if unavailable); IV corticosteroids for acute severe autoimmune hepatitis; immediate transplant evaluation for Wilson disease; heparin, then TIPS, for Budd-Chiari.
Give single-dose activated charcoal when acetaminophen was ingested within 4 hours; after a single acute ingestion, a level above 150 mcg/mL at 4 hours on the Rumack-Matthew nomogram indicates possible hepatotoxicity.
Hyperacute ALF (acetaminophen, hepatitis A or E, ischemia) carries the highest cerebral edema risk but the best spontaneous survival; subacute ALF (often idiosyncratic DILI) has less edema but poorer survival without transplant.
Lactulose, rifaximin, routine ICP monitoring and therapeutic hypothermia lack conclusive evidence in ALF and are not routinely recommended.
Start enteral nutrition if oral intake is not expected within 5–7 days, with protein 1.0–1.5 g/kg/day; consider delaying protein 24–48 hours when ammonia exceeds 150 µmol/L with encephalopathy.
About half of patients with ALF undergo liver transplantation, with 1-year post-transplant survival around 84% in the United States.
Encephalopathy is the alarm: the moment an acute liver injury makes the patient confused, it has become liver failure — and a transplant-center call.
Sources · Shingina A et al. Acute Liver Failure Guidelines (ACG Clinical Guideline). Am J Gastroenterol 2023;118:1128–1153 · Merck Manual Professional — Acetaminophen Poisoning · Acetadote (acetylcysteine) injection prescribing information, Jul 2025 — DailyMed (3-bag and 2-bag regimens) · MDCalc — King's College Criteria for Acetaminophen Toxicity · Starter sheet built from the verified AGACNP fact map (facts reviewed 2026-10-15).