Snapshot A 16-year-old girl is brought to the emergency room by her parents, who found a half-empty bottle of acetaminophen in her bathroom. She told her parents that she had been feeling depressed and took the pills this morning. Since then, she has had increased abdominal pain, generalized fatigue, and some nausea and vomiting. On physical exam, she is noted to be lethargic with right upper quadrant pain. On laboratory examination, she has elevated liver enzymes as well as elevated acetaminophen levels. She is admitted to the intensive care unit for close monitoring and started on N-acetylcysteine. (Acetaminophen overdose) 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 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 Pathogenesis mechanism cerebral edema is secondary to both vasogenic factors (increased cerebral blood flow) and cytotoxic edema (↑ ammonia and glutamine) live 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 most effective therapy Complications Infections often related to invasive procedures during course of hospital stay Seizures Hemorrhage Acute renal failure