Acute Liver Failure

Background

• 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

Evaluation

• 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 

Management

• 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