Acute Liver Failure

• Triad of abnormal liver tests + encephalopathy + coagulopathy (INR>1.5) in a patient without known liver disease.
• If no encephalopathy or coagulopathy, then termed acute liver injury

• Etiologies include:
  • Drugs/toxin (acetaminophen causes >40% in USA, Amanita mushrooms, antibiotics, antiepileptics, herbs/OTC, CCly, fluorinated hydrocarbons, isoniazid)
  • Viral (HBV, HAV, HEV; rarely EBV, CMV, HSV.) Hepatitis C does not result in acute liver failure (although it does cause acute liver injury.)
  • Autoimmune hepatitis (usually initial presentation)
  • Vascular (Budd-Chiari, ischemic hepatitis, other venoocclusive disease)
  • Metabolic (Wilson’s disease, acute fatty liver of pregnancy (AFLP — HELLP, Reye’s)
• The following are NOT causes of ALF but may increase risk: alcohol, malnutrition, underlying chronic liver disease (e.g., chronic hepatitis C, iron overload/hemochromatosis, fatty liver disease, alpha-1-antitrypsin deficiency, PBC, PSC)
• Prognosis: High mortality without transplant. Most important factor for prognosis is etiology.
  • Better prognosis: acetaminophen, hepatitis A, AFLP, ischemia. If time from symptoms to encephalopathy is less than 7 days, almost always related to acetaminophen.
  • Bad prognosis: Wilson’s disease, drugs other than acetaminophen, autoimmune, HBV, idiopathic

If suspect ALF, IMMEDIATELY contact liver transplant team. Consider ICU-level care for neurologic monitoring, hemodynamic and ventilator support, and renal replacement therapy with CVVH. Management centers on supportive care particularly to reduce cerebral edema and infections (the two most common immediate causes of death in ALF patients), with preparation for liver transplantation if necessary.

• Workup: Viral serologies (PCR), autoimmune hepatitis serologies (ANA, ASMA, AMA, IgG), ceruloplasmin and urine copper, ammonia level, toxicology screen (APAP levels q1-2hr until peak), imaging (RUQ U/S w/ doppler), +/- liver biopsy
• Start NAC in all patients with acute liver injury and coagulopathy regardless of etiology, and in every patient with APAP-induced acute liver injury regardless of degree of encephalopathy. Increases transplant-free survival.
• General treatment principles

* Cerebral edema with elevated intracranial pressure, risk of herniation

• Intracranial hemorrhage secondary to coagulopathy
• Progressive encephalopathy

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• Low threshold for non-contrast head CT to evaluate degree of cerebral edema and to rule out intracranial hemorrhage
• Low threshold to intubate if altered mental status
• Check serum ammonia level upon admission (>200 increases likelihood of intracranial hypertension)
• Mannitol 0.25-0.5 g/kg Q6H if serum osmolality <320 mOsm/L.
• Hypertonic saline for goal sodium > 145 mmol/L, temperature control (do not warm if hypothermic)
• Minimize IV fluid administration
• Goal ICP < 25 mmHg, CPP 50-80 mmHg (although ICP monitoring is no longer commonly used). Use systemic MAP >75 as a surrogate.

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* Liberal use of vasopressors (Norepinephrine, inotropy if needed) to increase

• IV fluids are not recommended for CV support given concern for increasing risk of cerebral edema

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* Hypoglycemia (from liver failure)

• hypophosphatemia (from rapid liver regeneration)
• hyponatremia (from renal dysfunction)
• lactic acidosis (from liver necrosis)

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• Dextrose gtt,
• Phosphorus repletion
• Hypertonic saline to increase serum sodium (to reduce cerebral edema)
• Early RRT (CVVH better than iHD even if HD stable)

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* Typically, INR does not predict bleeding risk. It may not be necessary to correct even for invasive procedures, but the risks/benefits of correction need to be discussed with proceduralist.

• Platelets and fibrinogen likely predict bleeding risk and should be corrected for invasive procedures.
• High risk for DVT, but given risk of bleed, avoid anti-platelet agents. Use lower extremity sequential compression device.

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* Pan culture with surveillance cultures Q48h

• Low threshold for antibiotic prophylaxis with moxifloxacin if hemodynamically stable. Consider IV antibiotics if critically ill

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• Initiate specific treatment if specific cause is known or highly suspected (i.e., initiate therapy while work-up pending and then stop if testing is negative): NAC for acetaminophen toxicity; entecavir or tenofovir for HBV; acyclovir for HSV; steroids for autoimmune hepatitis; delivery for AFLP; TIPS, thrombolysis, or surgical decompression for acute Budd-Chiari; activated charcoal, NAC, silibinin (not FDA approved) and possibly penicillin G for Amanita poisoning; chelation for Wilson’s disease
• Intracranial hypertension: Pathogenesis unclear, thought to be due to systemic/local inflammation leading to “leaky” blood-brain barrier, circulating neurotoxins (ammonia), hyponatremia decreasing oncotic pressure. Cerebral uncal herniation is the cause of death in many patients with ALF.
• King’s College Criteria: Used to select patients for transplant, takes into account age, cause, encephalopathy, coagulopathy.

• The patient should be evaluated by a liver transplant team as early as possible. If not at a transplant center, discuss the patient with a liver transplant center and consider early transfer before progression to stage III/IV encephalopathy.
• High risk for cerebral edema and herniation.