What is the next best step in managing a patient with suspected infectious mononucleosis and elevated liver enzymes?

Management of Suspected Infectious Mononucleosis with Elevated Liver Enzymes

In patients with suspected infectious mononucleosis and elevated liver enzymes, routine abdominal ultrasound is not indicated, and management should focus on supportive care with serial monitoring of liver function tests only if clinically indicated. 1

Initial Diagnostic Confirmation

• Confirm infectious mononucleosis diagnosis with a rapid heterophile antibody test (monospot), which has 87% sensitivity and 91% specificity 2
• If the heterophile test is negative but clinical suspicion remains high (particularly in the first week of illness or in children under 5 years), order Epstein-Barr viral capsid antigen-antibody testing for definitive diagnosis 2, 3
• Obtain a complete blood count with differential looking for >40% lymphocytes and >10% atypical lymphocytes, which supports the diagnosis 2, 3

Understanding the Liver Enzyme Elevation Pattern

• Elevated liver enzymes occur in the majority of infectious mononucleosis patients: aspartate transaminase (57%), alanine transaminase (62%), alkaline phosphatase (65%), and bilirubin (16%) 1
• The presence of elevated liver enzymes actually increases clinical suspicion for infectious mononucleosis when the heterophile antibody test is negative 2
• These elevations are typically mild to moderate and self-limited, with median time to resolution of 8 weeks (range 6-12 weeks), though some cases may take >6 months 1

Role of Abdominal Ultrasound

Routine abdominal ultrasound to evaluate elevated liver enzymes in infectious mononucleosis is not required in immunocompetent patients. 1

• Ultrasound should only be considered if there are specific clinical concerns such as:

  • Severe right upper quadrant pain suggesting acute acalculous cholecystitis (rare complication, predominantly in young women) 4
  • Signs of cholestasis with markedly elevated alkaline phosphatase and bilirubin 4
  • Clinical concern for splenic rupture (abdominal trauma, severe abdominal pain) 3

• Clinical hepatomegaly occurs in 35% and splenomegaly in 44% of patients, but imaging findings do not change management in uncomplicated cases 1

Management Algorithm

For Immunocompetent Patients with Subclinical Liver Enzyme Elevation:

• Do not perform serial liver function tests following initial abnormalities 1
• Provide supportive care with rest, hydration, and symptomatic treatment 2, 3
• Advise complete avoidance of contact sports and strenuous exercise for 8 weeks from symptom onset or while splenomegaly persists 2, 3
• Reassure patients that liver enzyme elevations are expected and typically resolve without intervention 1

For Patients with Symptomatic Liver Involvement:

• If cholestatic pattern develops (elevated alkaline phosphatase >3× ULN, rising bilirubin, right upper quadrant pain), consider ultrasound to evaluate for acute acalculous cholecystitis 4
• Monitor for signs of hepatic decompensation (jaundice, coagulopathy, encephalopathy), though decompensated liver disease has not been reported in immunocompetent patients with infectious mononucleosis 1

For Immunosuppressed Patients:

• These patients are at higher risk of severe disease and significant morbidity 2
• Consider more aggressive monitoring and specialist consultation, as standard evidence applies primarily to immunocompetent populations 1, 2

Important Clinical Pitfalls to Avoid

• Do not routinely order abdominal ultrasound for elevated liver enzymes in infectious mononucleosis - this practice is not supported by evidence and does not change management 1
• Do not perform serial liver function tests in asymptomatic patients with initial mild elevations - resolution takes weeks to months, and repeated testing adds no clinical value 1
• Do not prescribe routine antivirals or corticosteroids, as these are not recommended for uncomplicated infectious mononucleosis 2
• Do not allow return to contact sports before 8 weeks, as splenic rupture occurs in 0.1-0.5% of cases and is potentially life-threatening 3

When to Reassess or Refer

• If liver enzymes remain elevated beyond 6 months, consider alternative diagnoses and evaluate per standard elevated transaminase algorithms 5
• If ALT increases to >5× ULN or bilirubin >2× ULN, repeat testing within 2-3 days and consider hepatology referral 6, 5
• If signs of synthetic dysfunction develop (elevated INR, low albumin), urgent hepatology consultation is warranted 5