Drug-induced hepatitis is a major cause of acute liver failure. Which medication is the leading cause?

• A. Dextromethorphan
• B. Benadryl
• C. Acetaminophen
• D. Ibuprofen

Answer: (C)

The main concept is that acetaminophen is the most common drug cause of hepatitis leading to acute liver failure. In the liver, most acetaminophen is safely processed, but a portion is converted by liver enzymes into NAPQI, a highly reactive metabolite. Under normal dosing, NAPQI is quickly neutralized by glutathione. When someone overdoses, or glutathione stores are depleted (as can happen with chronic alcohol use, malnutrition, or preexisting liver disease), NAPQI accumulates and binds to liver cells, causing hepatocyte injury and necrosis that can progress to acute liver failure. Because acetaminophen is present in many OTC and prescription products, total daily intake can unintentionally exceed safe limits, especially if multiple products are used simultaneously. Early, nonspecific symptoms may be followed by marked increases in liver enzymes and, in severe cases, coagulopathy or hepatic encephalopathy. An antidote, N-acetylcysteine, helps by restoring glutathione stores if given promptly after overdose.

Other medications listed are not the leading culprits for drug-induced hepatitis and acute liver failure; they can have other adverse effects, but acetaminophen remains the most common cause in this scenario.