Most Common Drug Cause of Acute Liver Failure
Acetaminophen (paracetamol) is unequivocally the most common drug cause of acute liver failure, accounting for approximately 50% of all acute liver failure cases in the United States and representing 22% of emergency liver transplantation indications in France. 1, 2, 3
Epidemiological Evidence
The guideline evidence is definitive on this point:
- Acetaminophen-induced hepatotoxicity (whether intentional or unintentional) is the most common cause of severe acute liver failure requiring emergency liver transplantation. 1
- Among drug causes, acetaminophen far exceeds all other medications, with "other drugs" (antimicrobials, antiepileptics, and statins) collectively accounting for only 9.4% of acute liver failure cases. 1
- Acetaminophen overdoses carry a 30% mortality rate once acute liver failure develops, making it the largest single cause of death in acute liver failure registries. 3
Comparison with Other Listed Drugs
Among the specific options provided:
- Atorvastatin (a statin): Falls into the "other drugs" category representing only 9.4% collectively with antimicrobials and antiepileptics. 1
- Nimesulide (an NSAID): NSAIDs rarely cause liver injury and are not a significant cause of acute liver failure. 4
- Methotrexate: Typically causes chronic liver injury rather than acute liver failure and is not mentioned as a common cause in the guidelines. 1
- Ampicillin-clavulanic acid: Falls into the antimicrobial category within the 9.4% "other drugs" group. 1
Clinical Significance and Mortality Impact
The dominance of acetaminophen as a cause has critical prognostic implications:
- Transplant-free survival for acetaminophen-induced acute liver failure is 50%, which is actually better than most other drug-induced causes (which have <25% transplant-free survival). 1
- Despite this relatively better prognosis, acetaminophen still causes an estimated 500 deaths annually in the United States due to its overwhelming frequency. 5
- Nearly half of acetaminophen-related acute liver failure cases are unintentional, resulting from therapeutic misadventure rather than suicide attempts. 3
Key Clinical Pitfall
The critical error is failing to recognize acetaminophen toxicity early and delaying N-acetylcysteine administration. N-acetylcysteine should be initiated immediately without waiting for serum acetaminophen levels in any suspected case, as it significantly reduces mortality (from 6% to 0.7%) and hepatotoxicity (from 58% to 18%). 1, 6
Answer: a. acetaminophen