Acute Liver Failure

Acute Liver Failure  (ALF)– Judd Heideman , Hannah Lomzenski


  • Elevated aminotransferases
  • INR 1.5
  • Hepatic encephalopathy/altered mental status
  • Timing/onset < 28 weeks (otherwise consider acute-on-chronic liver failure/cirrhosis)
  • Acute liver injury (ALI) = elevated aminotransferases + INR >1.5 but NO hepatic encephalopathy (see above)
  • Pts with acute presentation of chronic autoimmune hepatitis, hepatitis B infection, Wilson disease, and Budd-Chiari syndrome are considered to have ALF if they develop HE, despite the presence of a pre-existing liver disease in the context of appropriate abnormalities in liver blood tests and coagulation profile
  • For DILI, consider recently added medications
  • Drugs Associated with DILI (search LiverTox database for the pts meds and likelihood of DILI)
    • Hepatocellular pattern: acarbose, Acetaminophen, Allopurinol, Amiodarone, Baclofen, Bupropion, Fluoxetine, HAART (Nevirapine), Kava kava, Isoniazid, Ketoconazole, Lisinopril, Losartan, Methotrexate, NSAIDs, Omeprazole, Oxacillin/Nafcillin, Paroxetine, Pyrazinamide, Propylthiouracil, Rifampin, Risperidone, Sertraline, Statins, Tetracycline, Trazodone, Valproic Acid
    • Mixed pattern: Amitriptyline, Azathioprine, Captopril, Carbamazepine, Clindamycin, Cyproheptadine, Enalapril, Flutemide, Nitrofurantoin, Phenobarbital, Phenytoin, Sulfonamides, Trazodone, Verapamil
    • Cholestatic pattern: Amoxicillin-clavulanic acid, Anabolic steroids, Chlorpromazine, Clopidogrel, Oral contraceptives, Erythromycins, Estrogens, Irbesartan, Mirtazapine, Phenothiazines, Terbinafine, Tricyclics


Common Etiologies of Acute Liver Failure

Acetaminophen (most common in US)

DILI (see DILI chart below)

Viral Hepatitis (most common worldwide): HAV, HBV, HEV

Autoimmune Hepatitis

Ischemia (Shock Liver)

Budd Chiari

Wilson Disease

Malignant Infiltration


Mushroom (Amanita phalloides) poisoning

Acute fatty liver of pregnancy or HELLP

Heat stroke (can be seen w/MDMA use)





  • Consult hepatology early! (assist with workup AND for transplant evaluation)
  • Labs:
    • CBC w/diff, CMP, Mg, Phos, T&S, BCx, UCx
    • PT/INR, aPTT, Fibrinogen (to assess for DIC/coagulopathy)
    • Amylase, lipase (to look for complications of ALF like pancreatitis)
    • Acetaminophen level (needs to be drawn at least 4hrs after last known ingestion)
    • Salicylate level, UDS
    • Viral Hepatitis Serologies
    • HAV IgM  (“Hepatitis A Pnl”), HBV sAg, sAb, cIgM (all in “Hepatitis B Panel”), HCV IgG (“Hepatitis C IgG”; consider PCR Qt if HCV IgG positive), Hepatitis D if known HBV (Misc Reference Test), Hepatitis E if travel to southeast Asia or pregnant (“Hepatitis E IgM- ARUP”)
    • EBV Qt, CMV Qt, HSV 1/2 Qt, VZV IgM/IgG
    • Beta-hCG for females of childbearing age
    • ANA, ASMA
    • Anti-LKM-1 Ab associated with more indolent autoimmune hepatitis/chronic liver disease (type 2 autoimmune hepatitis) and generally does not cause ALF
    • ABG with arterial lactate, ammonia 
    • Arterial ammonia >124 predicts mortality and CNS complications (e.g., need for intubation, seizures, cerebral edema)
    • HIV p24 Ag and HIV 1/2 Ab
  • Imaging:
    • RUQ abdominal ultrasound with doppler (important to assess vasculature!)
    • Consider CT with contrast in patients with normal renal function and high suspicion of Budd-Chiari syndrome or malignancy with negative ultrasound  (better for assessing the hepatic veins) and helps with transplant evaluation
    • Consider TTE to rule out cardiac dysfunction; helpful for transplant consideration


Criteria for Transplantation:

  • King’s College criteria:  helps identify patients needing transplant referral/consideration
    • ALF due to acetaminophen:
      • Arterial pH <7.3 after resuscitation and >24 hr since ingestion, OR
      • Lactate >3, OR
      • HE > grade 3, SCr >3.4, and INR >6.5
  • ALF not due to acetaminophen: INR > 6.5 OR 3 of the 5 following criteria:
    • Indeterminate etiology, drug-induced hepatitis
    • Age <10 or >40
    • Interval of jaundice to encephalopathy >7 days
    • Bilirubin > 3 or INR >3.5
  • No role for MELD-Na in acute liver failure 



  • Any pt with concern for ALF should be cared for in MICU
  • Pts with ALF die acutely from hypoglycemia, cerebral edema, and infection
  • ABC’s:
    • Intubate for GCS <8, Grade 3 or 4 HE
    • IVF resuscitation with isotonic crystalloid (most pts are volume deplete; avoid hypotonic fluids due to risk of cerebral edema)
    • Vasopressive agents for persistent hypotension (norepinephrine preferred)
  • Monitoring:
    • Q1-2h neuro checks, Q1-2h glucose checks
    • Q8h INR (no mortality benefit from empiric FFP/coag products)
    • BID BMP, daily Mg, P
    • Daily Hepatic Function Panel (generally no need for more frequent trending)
  • Treatment of Primary Injury
    • IV N-acetylcysteine - improves transplant-free survival even in patients WITHOUT acetaminophen induced acute liver failure
      • Initial loading dose = 150mg/kg over 1 hour, then 50mg/kg/hr for 4 hours, then 100mg/kg/hr for 16 hours​​​​​​​
      • Patients with early stage hepatic encephalopathy (grade I/II) have increased transplant free survival, while those with grade III/IV do not
    • See below for etiology-specific treatment; hepatology consult for LT eval
    • Early toxicology consultation if suspected ingestion/overdose
      • For acute management contact Poison Control 800-222-1222
  • Treatment of Secondary Complications
    • Infection: abx only if progressing HE, signs of infection, or development of SIRS; ppx abx do not reduce mortality
    • Cerebral edema/increased ICP:  elevated HOB to 30 degrees, quiet and dimly lit room, minimize IVF, goal Na 145-155, hyperventilation if concern for impending herniation. Consider 3% saline (500mL) and/or mannitol (1g/kg, 20%) for pt at highest risk (serum ammonia >150, grade III/IV HE, ARF, vasopressor support
    • Seizures: phenytoin (no evidence to support seizure ppx)
    • Renal Failure: early CRRT if persistent Metabolic Acidosis, Volume Overload, Hyperammonemia, falling UOP
    • Coagulopathy: IV Vit K; products for invasive procedures or active bleeding only
  • Additional Supportive Care
    • PPI for bleeding ppx
    • Enteral nutrition within 2-3 days; avoid TPN if possible; avoid NG feeds if progressive HE; NG should only be placed w/ intubation as gagging increases ICP
    • Avoid sedation as able; if sedation required, prefer propofol for better neuro exams to evaluate encephalopathy
    • Lactulose possibly helpful in the early stages of encephalopathy


Specific Management by Etiology:

  • Acetaminophen – IV N-acetylcysteine per protocol, look up Rumack-Mattew Nomogram and consult with tox; ideally, start NAC <8 hours after ingestion for best results (hepatotoxicity develops 12 hours post-ingestion)
    • Search “N-acetylcysteine” and select order set “Acetaminophen overdose”
    • Plan for serial acetaminophen level, INR, LFTs to be drawn 2 hours before the end of each N-acetylcysteine bag
  • Amanita phalloides – PO charcoal, IV penicillin, IV acetylcysteine
  • AFLP/HELLP – delivery
  • Autoimmune – IV steroids following approval by hepatology. Azathioprine generally deferred until cholestasis resolved
  • HAV/HEV – supportive care
  • HBV – nucleoside analogue; orthotopic liver transplant
  • HCV – consider treatment if no viral clearance
  • Budd-Chiari – anticoagulation, consider stent before TIPS
  • HSV – acyclovir
  • Wilson’s – plasma exchange; orthotopic liver transplant


Additional Information


  • Hyperacute (<7 days) = better prognosis
    • Cerebral edema common
  • Subacute (<28 days) = poorer prognosis
    • Renal failure, portal hypertension more common
  • By Etiology:
    • Acetaminophen: 60% survival without transplant (100% if NAC started within 16 hrs)
    • Other drug related injury: 30% survival without transplant
    • Hepatitis A: 60% survival without transplant
    • Acute Hepatitis B: 25% survival without transplant