What is the most common cause of acute liver failure in the United States?

• A. Acetaminophen overdose
• B. Alcoholic hepatitis
• C. Viral hepatitis
• D. Autoimmune hepatitis

Answer: (A)

Acetaminophen overdose is the leading cause of acute liver failure in the United States because acetaminophen is so widely used and has a very small margin between safe and toxic doses. In an overdose, the liver generates large amounts of the toxic metabolite NAPQI, which depletes glutathione and damages hepatocytes, especially in the central (zone 3) areas of the liver. This pattern can rapidly progress to fulminant liver failure with jaundice, coagulopathy, and hepatic encephalopathy. Although alcoholic hepatitis, viral hepatitis, and autoimmune hepatitis can cause acute injury, they are less commonly the cause of acute liver failure in the US. Early use of N-acetylcysteine replenishes glutathione and detoxifies NAPQI, improving outcomes, and severe cases may require transplant evaluation.