Gastrointestinal · Year 2 · from Gastrointestinal
Case 3: Acute Liver Failure from Acetaminophen Overdose
Patient Presentation
Demographics: 19-year-old female
Chief Complaint: Brought to ED by parents with confusion and vomiting
History of Present Illness: The patient was found by her parents appearing confused with multiple episodes of vomiting. Empty acetaminophen bottles were found in her room. She reportedly has been depressed after a recent breakup. Her roommate states she may have ingested pills "a couple days ago." Initial presentation was 48 hours after ingestion.
Past Medical History: Depression, anxiety
Medications: Sertraline 100 mg daily
Physical Examination
- Vital Signs: BP 92/58 mmHg, HR 118 bpm, Temperature 36.2C, RR 24/min
- General: Somnolent, jaundiced young female
- HEENT: Icteric sclerae, poor oral hygiene
- Cardiovascular: Tachycardic, regular
- Abdomen: Tender right upper quadrant, liver edge not palpable (liver shrinkage)
- Neurologic: Confused, slow to respond, asterixis present; GCS 12 (E3V4M5)
Workup and Results
- Liver Function Tests: AST 8,420 U/L, ALT 6,850 U/L (massively elevated), Total bilirubin 4.8 mg/dL
- INR: 6.8 (severely elevated)
- Arterial pH: 7.22 (acidosis)
- Lactate: 8.4 mmol/L
- Creatinine: 2.8 mg/dL (acute kidney injury)
- Ammonia: 185 mcmol/L (elevated)
- Acetaminophen Level: 18 mcg/mL (may be low or undetectable in late presentation despite toxicity)
- Blood Glucose: 58 mg/dL (hypoglycemia from impaired gluconeogenesis)
Diagram showing acetaminophen metabolism pathway: at therapeutic doses, glucuronidation and sulfation predominate; in overdose, CYP2E1 generates toxic NAPQI which depletes glutathione and causes hepatocyte necrosis. N-acetylcysteine (NAC) replenishes glutathione.
Image Source: Wikimedia Commons, CC BY-SA 3.0
Diagnosis
Acute Liver Failure due to Acetaminophen Overdose
Clinical Correlation
Acute liver failure is defined by coagulopathy (INR >/=1.5) and hepatic encephalopathy in a patient without pre-existing liver disease. Acetaminophen is the leading cause (50% in US). Acetaminophen is normally metabolized by glucuronidation and sulfation. In overdose, these pathways saturate, and CYP2E1 generates the toxic metabolite NAPQI. NAPQI is normally detoxified by glutathione, but glutathione depletion allows NAPQI to cause massive hepatocyte necrosis. Late presentation (>24 hours) is concerning because the acetaminophen level may be low despite massive liver injury already underway. King's College Criteria guide transplant listing: pH <7.3 after resuscitation, OR combination of grade 3-4 encephalopathy + INR >6.5 + creatinine >3.4 mg/dL.
Treatment
- ICU admission immediately
- N-acetylcysteine (NAC): Essential even in late presentation; replenishes glutathione, improves outcomes
- IV NAC: 150 mg/kg over 1 hour, then 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours
- Glucose infusion to prevent/treat hypoglycemia
- Monitor for cerebral edema: Head elevation, avoid agitation, hypertonic saline/mannitol if needed
- Fresh frozen plasma ONLY for invasive procedures or active bleeding (not to correct INR - it obscures prognosis)
- Contact liver transplant center immediately
- King's College Criteria assessment - this patient meets criteria (pH <7.3, encephalopathy, elevated INR and creatinine)
- Renal replacement therapy if needed
- Psychiatric evaluation when stable