S5107 Acute Cholestatic Hepatitis Due to Epstein-Barr Virus in a Healthy Young Adult: A Rare Diagnostic Challenge

Introduction: Epstein–Barr virus (EBV) infection typically presents as infectious mononucleosis with mild elevations in liver enzymes. However, marked hyperbilirubinemia and transaminitis as the predominant manifestation is uncommon and often under-recognized, frequently prompting extensive diagnostic evaluation before the correct diagnosis is established. Case Description/Methods: A 23-year-old previously healthy man presented with 3 days of epigastric/RUQ pain, nonbloody nonbilious vomiting, and 1 day of visible jaundice, preceded by several weeks of fatigue and chills without fever. He denied alcohol use and hepatotoxic drug exposures. On exam he was jaundiced but non-toxic; no asterixis or palpable hepatosplenomegaly was noted. Initial labs demonstrated aspartate aminotransferase (AST) 521 U/L, alanine aminotransferase (ALT) 546 U/L, alkaline phosphatase 195 U/L, total bilirubin 9.3 mg/dL (direct 6.1 mg/dL), GGT 139 U/L, and a reactive lymphocytosis with atypical lymphocytes. Over 48 hours in hospital, AST declined to 436 U/L while ALT transiently rose to 580 U/L and total bilirubin fell to 6.9 mg/dL. Comprehensive evaluation ruled out hepatitis A/B/C/E, HSV, CMV, autoimmune hepatitis (negative ANA, ASMA, LKM, SLA/LP), Wilson disease (normal ceruloplasmin). Imaging (computed tomography (CT), ultrasound, and MRCP) showed no biliary obstruction, but mild splenomegaly (14 cm) was noted. EBV Viral Capsid Antigen (VCA) IgM and EBV DNA polymerase chain reaction were positive with negative VCA IgG and EBNA IgG confirming acute infection. He received supportive care—hydration, rest, and avoidance of hepatotoxins—and was discharged from hospital in stable condition. Outpatient follow-up in 2 weeks demonstrated continued symptomatic improvement and downward‐trending LFTs. Discussion: Cholestatic hepatitis is a rare and often under-recognized manifestation of primary Epstein–Barr virus (EBV) infection, reported in fewer than 5% of cases. The underlying pathogenesis is thought to be immune-mediated, driven by T-cell–induced inflammation rather than direct viral cytotoxicity. In affected patients, imaging typically reveals no biliary obstruction, and serologic testing for other hepatotropic viruses and autoimmune markers is negative—features that should prompt early consideration of EBV in the differential diagnosis. Confirmation is readily achieved through noninvasive serologic testing, EBV viral capsid antigen (VCA) IgM serology. Management is primarily supportive, and the clinical course is typically self-limited, with spontaneous resolution and excellent prognosis.