S5803 The Perfect Storm: Aspirin-Induced Liver Injury in Epstein-Barr Virus Mononucleosis Complicated by Cold Agglutinin Hemolytic Anemia

Introduction: Epstein-Barr virus (EBV) commonly affects children and young adults, usually resulting in a self-limited infectious mononucleosis syndrome. Cold agglutinin hemolytic anemia is an uncommon complication of EBV infection, with several cases previously reported. Severe liver injury in this setting is rarely seen. We describe here a unique case of severe hepatotoxicity, suspected secondary to aspirin use, in a patient with acute EBV infection complicated by cold agglutinin-mediated hemolysis. Case Description/Methods: A 25-year-old woman presented with a 4-day history of fever, malaise, and upper abdominal discomfort. She had taken aspirin for symptom relief 5 days prior to presentation and denied taking any other medications, alcohol, or other substances. Initial laboratory evaluation revealed a mixed hepatocellular-cholestatic liver injury pattern: aspartate aminotransferase (AST) 483 U/L, alanine aminotransferase (ALT) 360 U/L, alkaline phosphatase 188 U/L, total bilirubin 7.8 mg/dL (direct bilirubin 6.1 mg/dL). During hospitalization, her liver enzymes increased significantly (AST >717 U/L [above assay limit], ALT 958 U/L) and total bilirubin peaked at 15.4 mg/dL. She developed normocytic anemia with a hemoglobin nadir of 8.3 g/dL. Hemolysis was confirmed by undetectable undetectable haptoglobin levels (<8 mg/dL), elevated lactate dehydrogenase levels, and the presence of cold agglutinins. Both EBV PCR and heterophile antibody tests were positive. A liver biopsy demonstrated histopathologic features consistent with severe hepatitis due to drug-induced liver injury. Notably, her mental status remained intact throughout her hospital course. Due to initial diagnostic uncertainty and significant transaminase elevation, she was empirically treated with intravenous N-acetylcysteine. She subsequently received supportive care alone. On outpatient follow up, she was asymptomatic. Repeat laboratory testing showed resolved anemia and near normal liver function tests. Discussion: This complex case highlights a unique presentation of severe liver injury suspected to be triggered by aspirin in the setting of acute EBV infection complicated by cold agglutinin hemolysis. While Reye syndrome is a well-recognized clinical entity involving liver injury in children given aspirin for viral illness, this case suggests that young adults may also experience idiosyncratic liver toxicity in this setting, particularly in the immunologically active milieu of acute EBV infection.