S5681 Severe Drug-Induced Liver Injury From Chronic Stimulant Use Exacerbated by Over-The-Counter Cough Syrup

Introduction: Drug-induced liver injury (DILI) accounts for approximately 30% of acute liver failure cases in the U.S. Common precipitants include antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs), herbal or dietary supplements, and rarely amphetamines. Stimulants such as the combination of dextroamphetamine and amphetamine are widely used for attention deficit disorder (ADD). We present a case of severe DILI associated with the use of dextroamphetamine and amphetamine, where liver injury was exacerbated by a cough syrup containing dextromethorphan. Case Description/Methods: A 43-year-old woman with a history of asthma and ADD presented with nausea, vomiting, epigastric pain, and cough for several weeks. She denied use of alcohol, herbal supplements, or illicit drugs. Laboratory workup revealed: aspartate aminotransferase (AST) 3,764 U/L, alanine aminotransferase (ALT) 2,222 U/L, alkaline phosphatase (ALP) 160 U/L, total bilirubin 16.7 mg/dL, direct bilirubin 12.4 mg/dL, MELD-Na 21. Five months prior, liver function tests were: AST 370 U/L, ALT 528 U/L, ALP 143 U/L, total bilirubin 1.0 mg/dL. At that time, a comprehensive workup, including acute hepatitis panel, ANA, AMA, ASMA, and serologies for CMV, EBV, and HSV was negative. She had normal alpha-1 antitrypsin, ceruloplasmin, and ferritin, but urine toxicology was positive for amphetamines. MRI of the abdomen showed cirrhotic liver morphology, heterogeneous parenchyma, and areas of confluent fibrosis. Liver biopsy showed findings consistent with autoimmune hepatitis versus DILI. The patient disclosed a long-term use of dextroamphetamine and amphetamine (60 mg/day) for over 20 years. She had been advised to reduce the dose when her liver function started to decline but was unable to tolerate this. Notably, her liver function worsened after using a cough syrup containing dextromethorphan. She was started on a short course of corticosteroids with significant improvement (AST 228 U/L, ALT 448 U/L, ALP 85 U/L, total bilirubin 4.3 mg/dL, direct bilirubin 3.3 mg/dL), MELD-Na 13. The stimulant was discontinued indefinitely. Discussion: We illustrate a rare case of DILI in a patient with long-term, high-dose stimulant use. Amphetamines and dextromethorphan are primarily metabolized by CYP2D6. Dextromethorphan acts as a competitive inhibitor, potentially impairing amphetamine clearance and increasing toxicity. Clinicians should maintain a high index of suspicion for DILI in patients on stimulant therapy presenting with acute liver injury, particularly in the presence of interacting agents.