S3300 Acetaminophen Toxicity Amplified: Drug-Induced Liver Injury in a Malnourished Patient

Abstract

Introduction: Acetaminophen toxicity is a leading cause of acute liver injury and failure in the U.S. Excess acetaminophen results in formation of N-acetyl-p-benzoquinoneimine (NAPQI) which causes irreversible oxidative hepatocyte injury and cell necrosis. Treatment with N-acetylcysteine (NAC) replenishes glutathione stores which inactivate NAPQI. In a healthy adult, acetaminophen doses less than 4 g per 24 hours are considered safe. Toxicity from therapeutic doses of acetaminophen, in the setting of malnourishment, has been rarely reported and is presented here. Case Description/Methods: A 37-year-old female with a history of gastroparesis and chronic malnutrition was admitted for elevated liver enzymes on routine blood work. She reported symptoms of fatigue, nausea, and poor oral intake from suspected gastroparesis. She also admitted to taking 1300 mg of acetaminophen intermittently during the past week for myalgias. Exam revealed normal mentation without evidence of hepatic encephalopathy (HE), cachexia with a BMI of 15.2, and mild epigastric and left upper quadrant tenderness. Laboratory data (36 hours after last ingestion of acetaminophen) revealed an ALT of 1180 u/L, AST of 1950 u/L, ALP of 121 u/L, total bilirubin of 2.7 mg/dL, direct bilirubin of 2.5 mg/dL and INR of 1.6. Her acetaminophen level was 15.8 mcg/mL. A liver ultrasound was unremarkable. NAC was subsequently administered as per protocol 21 hour infusion. She was ruled out for other etiologies of acute liver injury. She never developed HE and her liver enzymes, along with INR, normalized at discharge. Discussion: This case highlights the lower threshold for toxicity of acetaminophen in a malnourished patient. In previous case reports, acetaminophen doses less than 2 g per 24 hours are listed as being safe in a nutritionally deficient patient. Our case questions this assertion given our patient ingested 65% of this amount. Evidence in the relatively limited pool of literature suggests that malnourished patients generally have low stores of glutathione, thereby limiting the metabolic clearance of acetaminophen ingested even at normal dosages, amplifying total acetaminophen levels, and leading to increased NAPQI. Prospective study is limited to rat models and single case reports. Fortunately, our patient was promptly treated with NAC and did not progress to liver failure. This case highlights the narrow therapeutic window of acetaminophen in malnourished patients, one that warrants close observation by clinicians.