What is EBV Hepatitis?
EBV hepatitis is liver inflammation caused by Epstein-Barr virus infection, characterized by elevated transaminases that are typically mild and self-limiting, though it can rarely present with severe hepatitis and cholestatic jaundice. 1
Clinical Definition and Pathophysiology
EBV hepatitis represents hepatobiliary involvement during acute EBV infection, where the virus causes liver inflammation with elevated liver enzymes, though the exact mechanism of hepatocyte injury remains incompletely understood. 1, 2
The condition differs significantly from classic infectious mononucleosis presentation—only 12% of patients with EBV hepatitis present with the classic triad of fever, pharyngitis, and lymphadenopathy. 3
EBV's ability to transform and immortalize B-lymphocytes underlies its pathogenic potential, though hepatitis represents direct liver involvement rather than lymphoproliferative disease. 4
Clinical Presentation Patterns
Typical Features
The majority of patients (88%) present with jaundice and clinical evidence of hepatitis, making it a key differential diagnosis in patients presenting with unexplained jaundice. 3
Splenomegaly is present in 88% of cases, which serves as an important clinical clue distinguishing EBV hepatitis from other causes of acute hepatitis. 3
A peripheral blood lymphocytosis is present in 100% of cases at presentation, often with atypical lymphocytes on blood smear. 1, 3
Age Distribution
EBV hepatitis affects an older age group compared to infectious mononucleosis, with nearly half of patients being aged more than 60 years. 3
The median age is 40 years (range 18-68 years), with 59% of patients over age 30. 3
Severity Spectrum
Most cases involve mild transaminase elevations that remain self-limited, with symptoms lasting a median of 8 weeks. 1, 3
Severe or fulminant hepatitis can occur but is rare, particularly in immunocompetent patients. 2
Cholestatic jaundice with marked hyperbilirubinemia can develop, especially in older patients, and may be accompanied by marked hyperferritinaemia (ferritin levels >5000 μg/L correlating with disease severity). 5, 6
Diagnostic Approach
Serologic Confirmation
Diagnosis requires serologic confirmation of acute EBV infection using VCA IgM antibodies as the primary marker, combined with elevated transaminases. 1
The acute infection pattern is indicated by positive VCA IgM (with or without VCA IgG) in the absence of EBNA antibodies. 1, 7
Heterophile antibodies (Monospot test) become detectable between days 6-10 after symptom onset, though false-negative results occur in approximately 10% of patients, especially children under 10 years. 1
Important Diagnostic Pitfalls
Due to antigenic cross-reactivity with other herpes viruses, serological assays may lack specificity—molecular diagnostic methods (EBV DNA PCR) are required for definitive confirmation when cross-reactivity is suspected. 8
False-positive heterophile tests can occur in leukemia, pancreatic carcinoma, viral hepatitis, and CMV infection. 1
Key Laboratory Findings
Elevated transaminases (ALT, AST) with variable patterns—typically less than 5-fold elevation, rarely exceeding 10-fold normal. 8
Cholestatic pattern possible with elevated alkaline phosphatase and gamma-glutamyl transferase. 5
Atypical lymphocytosis on peripheral blood smear is characteristic. 1
Differential Diagnosis
EBV hepatitis is listed as a key differential diagnosis for acute hepatitis in major guidelines, alongside drug-induced liver injury, autoimmune hepatitis, and other viral hepatitides. 9
Other Causes to Consider
CMV hepatitis, adenovirus, HIV, hepatitis A-E viruses, and Toxoplasma gondii can all cause mononucleosis-like illness with hepatitis. 1, 4
Drug-induced liver injury (DILI) is particularly important to exclude, as both DILI and EBV hepatitis are common in elderly patients. 9
Management
Antiviral therapy with aciclovir does not ameliorate the course of infectious mononucleosis or EBV hepatitis in otherwise healthy individuals. 1
Management is primarily supportive, including IV hydration and monitoring of liver function parameters (ALT, AST, bilirubin, INR). 2
The condition is self-limiting in immunocompetent patients, with most cases resolving spontaneously over 1-12 weeks. 3
Only 18% of patients require brief hospital admission. 3
Clinical Significance
EBV hepatitis accounts for 0.85% of patients presenting with jaundice or acute hepatitis in specialized jaundice clinics. 3
The diagnosis should be considered in all patients with unexplained hepatitis irrespective of age, particularly when lymphocytosis and/or splenomegaly are present. 3
In immunosuppressed patients, EBV testing is recommended for unexplained abnormal liver function tests, as chronic infection can develop. 9