Severe Hepatocellular Injury With Transaminases > 20,000 IU/L in Suspected Repeated Drug Ingestion Despite Undetectable Serum Levels

Acetaminophen toxicity is a leading cause of acute liver injury and is typically evaluated using serum acetaminophen levels and the Rumack-Matthew nomogram. However, this approach does not apply to repeated supratherapeutic ingestion or delayed presentation, where levels may be low or undetectable despite severe liver injury. We report a 38-year-old woman with alcohol use disorder who presented with epigastric pain, nausea, and vomiting and was found to have acute-on-chronic pancreatitis and marked hepatocellular injury. Her liver enzymes rapidly worsened, peaking at aspartate transferase (AST) 22,966 IU/L and alanine aminotransferase (ALT) 1,498 IU/L, while the serum acetaminophen level remained <10 µg/mL. Further history revealed repeated ingestion of approximately 9 g of acetaminophen daily for four to five days prior to admission. Intravenous N-acetylcysteine was initiated despite the undetectable level. Liver enzymes subsequently improved, and the patient remained hemodynamically stable without encephalopathy. This case highlights that an undetectable acetaminophen level does not exclude severe toxicity and emphasizes the importance of early empiric treatment when clinical suspicion is high.