S5892 Acute Liver Failure From Acetaminophen Toxicity in the Setting of Concurrent Alcohol and Rifampin Use

Introduction: Acetaminophen toxicity is a leading cause of acute liver failure in the United States. The concurrent use of CYP enzyme inducers and hepatotoxic agents presents a crucial consideration in the use of acetaminophen in certain patients. We present a case of acute liver failure attributed to acetaminophen use in a patient on rifampin with concomitant alcohol ingestion. Case Description/Methods: A 27-year-old man, with a medical history of Crohn’s disease, presented to the Emergency Department with acute onset abdominal pain, nausea, and vomiting. Approximately 2.5 months prior, he was incidentally found to have latent tuberculosis (TB) while being evaluated for biologic therapy. He subsequently started rifampin, with consistent adherence. The evening before his presentation, he reported consuming an unknown quantity of alcohol and took multiple acetaminophen tablets of unknown strength for abdominal pain. Several hours later, he awoke with acute onset vomiting and worsening severe abdominal pain. His initial labs were notable for aspartate aminotransferase/alanine aminotransferase/alkaline phosphatase 308/226/83 U/L, international normalized ratio 2.2, and total bilirubin (Tbili) 1.6 mg/dL. Abdominal imaging was notable for periportal edema with diffusely heterogenous hepatic parenchyma suggestive of acute hepatitis. The acetaminophen level was 96 mcg/mL ∼12 hours post-ingestion, and N-acetylcysteine (NAC) therapy initiated. Despite NAC, his labs worsened to alanine aminotransferase and AST over 7,000 U/L, international normalized ratio 6.2, and Tbili 11.1 mg/dL. He developed grade II hepatic encephalopathy and was transferred to a transplant center for transplant evaluation. Upon transfer, continuous venovenous hemofiltration (CVVH) was started for encephalopathy and hyperammonemia. With supportive management, the patient recovered without a need for transplantation. After discharge, he started ethambutol and moxifloxacin for latent TB treatment. Discussion: Our case emphasizes the elevated risk of severe hepatotoxicity from acetaminophen in combination with certain classes of medications. Rifampin induces CYP3A4 and CYP2E1, which increase the conversion of acetaminophen to its hepatotoxic metabolite, NAPQI. While rifampin alone has rarely been associated with fulminant liver failure, it is important to recognize its interaction with acetaminophen and potential toxicity. Furthermore, concurrent alcohol use can further exacerbate this potential. This case highlights the importance of understanding high-risk medication interactions in at-risk individuals using acetaminophen.