Case Presentation: A 21-year-old healthy Hispanic male presented to the hospital for evaluation of fever and sore throat for 4 weeks. He had no significant past medical history and he was not on any medications. His vital signs were within normal limits. Physical exam revealed icterus and no hepatosplenomegaly. The remainder of the physical exam was within normal limits. Initial workup revealed elevated liver function tests (alkaline phosphatase 522 IU/L; aspartate aminotransferase 592 IU/L; alanine aminotransferase 665 IU/L; gamma-glutamyl transferase 295 IU/L; total bilirubin 7.7 mg/dL; direct bilirubin 4.8 mg/dL). He had normal coagulation profile (prothrombin time 13.6 seconds, INR 1.2). He was admitted for further workup for new onset elevated liver function tests and bilirubin. Infectious workup, including cytomegalovirus (CMV) serology, syphilis screen, HIV antibodies, and serological tests for viral hepatitis A, B, and C were negative. Further workup revealed a positive heterophil antibody (Monospot) and serology for IgM against Epstein-Barr Virus (EBV) of 42.9 U/mL, which was in the intermediate range. EBV DNA plasma real-time polymerase chain reaction (qPCR) test showed 5900 IU/mL, a positive result. Abdominal computed tomography (CT) and ultrasound showed mild splenomegaly, 15.7 cm with normal liver echogenicity, and no focal lesions in the liver or gallbladder, and no intrahepatic or extrahepatic biliary dilatation or stones noticed. No biopsies were performed. He was empirically started on intravenous cefepime due to concern for acute ascending cholangitis upon admission and later stopped due to the confirmed diagnosis of infectious mononucleosis hepatitis due to EBV.

Discussion: Infectious mononucleosis (IM) is the best known acute clinical manifestation of Epstein-Barr virus (EBV). EBV is a widely disseminated herpesvirus that is spread by close contact between susceptible persons and asymptomatic EBV shedders. Most primary EBV infections throughout world are subclinical, however, if primary infection is delayed until adolescence or adulthood, about half of those infected will become symptomatic. It is estimated that 90-95% of adults are seropositive for EBV. Usually, primary EBV infection in children is asymptomatic with seroconversion. In adolescents and adults, the most common presentation is fatigue, fever, sore throat, and lymphadenopathy. Hepatosplenomegaly may be seen in more than 10% of patients. Rarer manifestations of IM include hemolytic anemia, thrombocytopenia, aplastic anemia, myocarditis and neurological complications. Hepatic involvement in IM is common, with about 80-90% of cases presenting with subclinical elevations in transaminases. However, acute hepatitis is a rare complication in adolescence, especially when presenting with jaundice. The mechanism of hepatic injury due to acute IM is not fully understood, however, may be moderated by infected CD8+ T cells, interferon γ, TNFα, Fas ligand, or cytotoxic T lymnphocytes.

Conclusions: Although Infectious mononucleosis due to EBV sometimes causes acute hepatitis, which is usually self-limiting with mildly elevated transaminases, but rarely with jaundice. Many patients, such as the one described here, presenting with acute IM hepatitis may not present with the typical symptoms of acute IM, but should be considered in the differential diagnosis, especially when lymphocytosis and/or splenomegaly are present.