Snapshot An 8-year-old boy is brought to the emergency room by his babysitter for sudden-onset vomiting. He had been feeling ill with headaches, fevers, and myalgias. Today, his parents gave him some anti-pyretics including acetaminophen and aspirin. When his babysitter arrived, he had progressive nausea with vomiting, diarrhea, and increased restlessness. On exam, he is lethargic with hepatomegaly. A head computed tomography shows cerebral edema and his laboratory evaluation reveals increased ammonia and liver enzyme levels. He is admitted to the intensive care unit for further management. (Reye syndrome) Introduction Overview liver failure results in coagulopathy and encephalopathy fulminant liver failure describes onset of encephalopathy within 8 weeks of hepatic injury in a previously healthy patient Epidemiology Risk factors drug-induced (most common) acetaminophen Wilson disease viral hepatitis hepatitis E virus in pregnant women autoimmune hepatitis Reye syndrome HELLP syndrome herbal and dietary supplements ginseng, germander tea, kawakawa, and Teucrium polium certain mushroom ingestions Amanita phalloides mushroom alcohol use ETIOLOGY Pathogenesis mechanism cerebral edema is secondary to both vasogenic factors (increased cerebral blood flow) and cytotoxic edema (↑ ammonia and glutamine) liver failure is often due to direct toxic effects (i.e., acetaminophen metabolite toxicity) Presentation Symptoms common symptoms encephalopathy abdominal pain right upper quadrant tenderness present but not always gastrointestinal bleeding melena hematemesis Physical exam inspection jaundice ascites papilledema due to increased intracranial pressure motion hepatomegaly Imaging Hepatic ultrasound indications help establish cause of liver failure findings ascites occlusion or patency of vessels liver mass Abdominal computed tomography (CT) indications exclude other intra-abdominal pathologies findings liver mass ascites hepatomegaly Head CT indications exclude other causes of altered mental status findings cerebral edema Studies Serum labs elevated prothrombin time/INR used to determine severity of coagulopathy ↓ platelets liver panel abnormalities ↑ aspartate aminotransferase (AST) ↑ alanine aminotransferase (ALT) ↑ alkaline phosphatase ↑ bilirubin ↑ ammonia etiology-specific tests autoimmune hepatitis antibodies (ANA and anti-smooth muscle antibody) acetaminophen levels drug screen serum free copper hepatitis viral panels Invasive studies liver biopsy contraindicated in coagulopathy can confirm diagnosis, including autoimmune hepatitis, malignancy, or viral hepatitis Differential Septic shock key distinguishing factor can also result in multi-organ failure typically does not have the laboratory changes seen in liver failure Treatment Management approach address underlying cause (see individual topics for comprehensive review of treatment) i.e. N-acetylcysteine for acetaminophen toxicity Medical supportive care modalities intracranial pressure monitoring treatment of cerebral edema treatment modalities mannitol treatment of coagulopathy modalities fresh frozen plasma recombinant factor VIIa platelet transfusion Surgical liver transplant indications irreversible liver damage the most effective treatment Complications Infections often related to invasive procedures during course of hospital stay Seizures Hemorrhage Acute renal failure