Snapshot A 3-year-old previously healthy boy is rushed to the emergency room for sudden-onset vomiting and lethargy. He was born at full-term without complications and had been meeting all milestones. Two weeks ago, he had headaches, myalgias, and fevers and tested positive for influenza A virus. At that time, his parents tried multiple anti-pyretic medications, including ibuprofen, acetaminophen, and aspirin. On physical exam, he is dehydrated and has hepatomegaly. Labs show increased liver enzymes and ammonia. A head computed tomography (CT) shows diffuse cerebral edema. He is admitted to the intensive care unit (ICU) and started on steroids. Introduction Clinical definition acute non-inflammatory hepatic encephalopathy resulting in fatty liver Epidemiology Demographics children very rare Risk factors viral infection treated with aspirin varicella influenza gastroenteritis rarely, vaccination with live viruses ETIOLOGY Pathogenesis aspirin metabolites inhibit mitochondrial enzymes disrupts oxidative phosphorylation and fatty-acid beta-oxidation pathways microvesicular fatty changes in the liver Presentation Symptoms nausea and sudden-onset vomiting diarrhea lethargy irritability restlessness delirium seizures coma Physical exam hepatomegaly minimal jaundice obtunded in severe cases permanent neurologic damage fixed and dilated pupils loss of oculovestibular reflexes imaging Computed tomography (CT) of brain diffuse brain swelling Studies Diagnostic testing diagnostic approach other causes of encephalopathy must be ruled out, including central nervous system infections studies serum labs ↓ blood glucose ↑ ammonia ↑ hepatic enzymes ↑ long-chain free fatty acid levels liver biopsy non-inflammatory fatty changes cerebral spinal fluid analysis normal Differential Inborn errors of metabolism, e.g., fatty-acid oxidation defects, urea cycle defects, etc. distinguishing factors typically presents in infancy genetic testing normal liver size Treatment Management approach avoid use of aspirin in children, except when necessary, e.g., Kawasaki disease treatment is largely supportive and neuro-protective First-line neuro-protection modalities mannitol glycerol dexamethasone Complications Permanent brain damage Death Prognosis Mortality < 20%