S5932 Transient Hepatitis in a Young Adult With False-Positive HBc IgM in the Setting of Acute EBV and COVID-19 Co-Infection: A Case Report

Introduction: False-positive hepatitis B core IgM antibody (anti-HBc IgM) results can occur in the setting of acute viral infections such as Epstein-Barr virus (EBV), cytomegalovirus (CMV) and COVID 19. These cross-reactive results can complicate the diagnosis of acute hepatitis. Awareness of such interactions is essential to avoid misdiagnosis and unnecessary invasive testing or treatment. Case Description/Methods: A 22-year-old previously healthy woman was admitted after a 2-day history of upper respiratory symptoms, high fever and body aches, scleral icterus, and positive home COVID-19 antigen test. Initial labs revealed elevated liver enzymes (alanine aminotransferase [ALT] 219 U/L, aspartate aminotransferase [AST] 250 U/L, alkaline phosphatase 276 U/L, and total bilirubin 3.29 mg/dL). Repeat labs on the second hospital day showed improvement: AST 171 U/L, ALT 143 U/L, alkaline phosphatase 312 U/L, and total bilirubin 2.2 mg/dL. A liver ultrasound was normal. A viral hepatitis workup was negative for hepatitis A, C, and E. HBV serology had a positive anti-HBc IgM and negative HBsAg, total anti-HBc, and HBsAb, raising concern for acute HBV. Both EBV viral capsid antigen (VCA) IgM and CMV IgM were positive with negative IgG initially. All other work up for liver diseases was negative. Follow-up testing showed: negative HBV DNA, negative total anti-HBc and negative anti-HBs, negative CMV PCR and repeatedly negative CMV IgG. EBV VCA IgM persisted, and seroconversion to positive EBV VCA IgG, confirming a recent EBV infection. All liver enzymes normalized and the acute hepatitis resolved without intervention. Discussion: This case illustrates the difficult interpretation of a positive anti-HBc IgM. Polyclonal B-cell activation and cross-reactivity during acute viral illness can yield misleading serologic profiles suggestive of acute HBV. In diagnosing HBV, it is essential to consider the full HBV serologic panel (HBsAg, anti-HBs, and HBV DNA levels). In cases where only the anti-HBc IgM is positive and there is a concurrent acute viral infection, a false-positive result should be considered. Repeat testing after the acute illness and HBV DNA testing can help clarify the patient's HBV status. In summary, clinicians should be aware of the potential for false-positive anti-HBc IgM results in patients with other acute viral infections. Comprehensive evaluation and follow-up testing are crucial to avoid misdiagnosis and ensure appropriate patient management.