Abstract
Epstein-Barr virus (EBV) and Hepatitis E virus (HEV) are two distinct viral pathogens known to affect the liver. While EBV commonly causes mild, self-limited hepatitis, and HEV is the leading cause of acute viral hepatitis globally, co-infection with both viruses is exceedingly rare. This case report describes a 55-year-old previously healthy male who presented with right upper quadrant abdominal pain and generalized fatigue. Laboratory investigations revealed markedly elevated transaminases and slightly increased bilirubin, suggesting mixed hepatocellular and cholestatic liver injury. Initial serologies showed positive EBV IgG and borderline IgM, confirmed by a low positive EBV DNA PCR. While awaiting HEV testing, the patient was managed supportively. On day four, HEV IgM returned positive and EBV DNA rose to 15,500 copies/mL, confirming concomitant infection. Imaging revealed periportal edema and splenomegaly with no biliary obstruction. Supportive care led to a steady clinical improvement and normalization of liver enzymes by day 14. The patient was discharged in stable condition with full clinical and biochemical recovery. This case highlights the importance of considering dual viral infections in patients with significant hepatic enzyme elevation and non-specific systemic symptoms. Although rare, concurrent EBV and HEV infection can present with significant liver inflammation but may still follow a self-limiting course in immunocompetent individuals. Awareness of such co-infections can prevent misdiagnosis, avoid unnecessary interventions, and emphasize the role of supportive care. Additionally, this case underscores the need for comprehensive viral screening when evaluating unexplained hepatitis in otherwise healthy individuals. Early recognition ensures appropriate management and favorable outcomes.