Elevated Liver Enzymes in Infectious Mononucleosis
In infectious mononucleosis, aminotransferases (AST and ALT) are the liver enzymes typically elevated, with transaminase levels rising to an average maximum of 5-fold above normal, peaking around 2 days after clinical onset and normalizing within approximately 20 days. 1
Pattern of Liver Enzyme Elevation
AST and ALT are the predominant enzymes elevated in EBV-associated hepatitis, showing a hepatocellular pattern of injury with levels typically reaching 5-fold the upper limit of normal 1
Alkaline phosphatase (ALP), gamma-glutamyltransferase (γ-GT), and bilirubin may also increase above normal values, though these elevations are less consistent and statistically less significant than transaminase elevations 1
Cholestatic features are common, occurring in 59% of patients with anicteric cholestatic liver disease, while frank jaundice occurs in only 6% of cases 1
The presence of elevated liver enzymes increases clinical suspicion for infectious mononucleosis when the heterophile antibody test is negative 2
Clinical Management Approach
Treatment is entirely supportive, as EBV-associated hepatitis is self-limited with complete recovery being the rule. 2, 1
Initial Assessment
Obtain complete blood count with differential looking for >40% lymphocytes and >10% atypical lymphocytes, along with rapid heterophile antibody testing 2
Order a complete liver panel including AST, ALT, alkaline phosphatase, GGT, total and direct bilirubin, and albumin to establish the pattern and severity of elevation 3, 4
If heterophile antibody test is negative but clinical suspicion remains high (especially with elevated liver enzymes), proceed with EBV viral capsid antigen-antibody testing, which is more sensitive and specific 2
Monitoring Strategy
No specific treatment is required for the hepatitis component - monitor liver enzymes every 1-2 weeks until normalization, which typically occurs within 20-30 days 1
Advise patients to avoid hepatotoxic medications and alcohol during the acute phase 3
Patients should not participate in athletic activity for 3 weeks from symptom onset due to splenomegaly risk, using shared decision-making for return to activity 2
Critical Pitfalls and Red Flags
Do not use corticosteroids or antivirals routinely - these are not recommended for uncomplicated infectious mononucleosis 2
Be vigilant for rare but serious complications including hemophagocytic lymphohistiocytosis (HLH), which presents with extremely elevated ferritin, triglycerides, and interleukin-2 levels requiring urgent immunosuppressive therapy 5
Acute acalculous cholecystitis is an atypical complication that typically resolves with conservative management; surgical intervention is rarely necessary 6
If ALT/AST levels exceed 5× ULN or bilirubin exceeds 3× ULN, or if liver enzymes fail to normalize within 3 months, consider hepatology referral to exclude alternative diagnoses 4
Special Populations
Immunosuppressed patients are at higher risk for severe disease and significant morbidity, requiring closer monitoring 2
Children younger than 5 years may have false-negative heterophile antibody tests, necessitating direct EBV serologic testing 2
Adults tested during the first week of illness may also have false-negative heterophile antibody results 2