Is EBV a Common Cause of Elevated Liver Enzymes?

Patient Presentation
An emergency medicine physician called a regional children’s hospital for consultation with a general pediatrician. His question was could a school age child who had elevated transaminase levels (2-3x normal), elevated bilirubin and mild clinical jaundice but no other clinical symptoms be infected by Epstein Barr Virus? The brief story was that the child had a fever for 2 days and the parent noted scleral icterus. There was no abdominal pain. The general pediatrician was fairly sure that EBV could cause these types of problems, and knew that it could cause splenomegaly, and was a major complication of solid organ transplants particularly liver transplants. However, the general pediatrician wasn’t sure of treatments so he offered the emergency room physician to be reconnected with a pediatric gastroenterologist. He assumed the consultation with the gastroenterologist went well, because he had told the emergency room physician to contact him if there were any problems contacting the gastroenterologist, and he had not heard back from the physician.


Infectious mononucleosis is caused by an Epstein-Barr Virus (EBV) infection causing the triad of fever, sore throat and adenopathy.

The differential diagnosis of clinical presentations similar to EBV includes:

  • Viral
    • Cytomegalovirus
    • Herpes simplex
    • Hepatitis A, B, C
    • HIV
    • Varicella
  • Bacterial/Spirochete
    • Brucellosis
    • Leptospirosis
    • Syphilis
    • Q fever
  • Miscellaneous
    • Autoimmune hepatitis
    • Drug side effects
    • Ischemia
    • Wilson Disease

Treatment for EBV infections is mainly supportive. Anti-viral medications such as ganciclovir are usually used for severe problems. Liver failure has been treated by transplant.
Refraining from activities which could cause abdominal trauma while splenomegaly is apparent is recommended as is medications that are hepatotoxic until liver function tests normalize.

Learning Point
EBV infections are usually asymptomatic with 90-95% of people by age 18 becoming seropositive.
EBV is known have many different clinical presentations which can be reviewed here.
A monospot test for EBV can be falsely positive and reasons for this can be reviewed here.

Gastrointestinal problems related to EBV include:

  • Mildly elevated transaminase levels (2-3x normal) that are asymptomatic clinically
  • Laboratory test abnormalities
    • Alkaline phosphatase – 60%
    • Bilirubin – 45%
  • Mild abdominal pain – 15%
  • Jaundice – < 5 %
  • Hepatitis (with moderate 5-10 x transaminase elevation) – 80-90%
  • Hepatosplenomegaly 6-14%
  • Splenomegaly 50-60%
  • Splenic rupture
  • Liver failure

Liver function test abnormalities occur usually during the second week of illness and resolve within 2-6 weeks.
Severe liver problems are rare but can occur and may be deadly. Fulminant cases are usually associated with a concomitant immunodeficiency.
Chronic EBV infections may also be implicated with autoimmune hepatitis and hepatocellular carcinoma.

Questions for Further Discussion
1. List other clinical presentations of EBV infections?
2. When do heterophil antibodies become positive after infection?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for this topic: Infectious Mononucleosis.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

Feranchak AP, Tyson RW, Narkewicz MR, Karrer FM, Sokol RJ. Fulminant Epstein-Barr viral hepatitis: orthotopic liver transplantation and review of the literature. Liver Transpl Surg. 1998 Nov;4(6):469-76.

Crum NF. Epstein Barr virus hepatitis: case series and review. South Med J. 2006 May;99(5):544-7.

Kelly DA. Current issues in pediatric transplantation. Pediatr Transplant. 2006 Sep;10(6):712-20.

ACGME Competencies Highlighted by Case

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

  • Practice Based Learning and Improvement
    12. Evidence from scientific studies related to the patients’ health problems is located, appraised and assimilated.
    13. Information about other populations of patients, especially the larger population from which this patient is drawn, is obtained and used.
    14. Knowledge of study designs and statistical methods to appraisal clinical studies and other information on diagnostic and therapeutic effectiveness is applied.
    16. Learning of students and other health care professionals is facilitated.

  • Interpersonal and Communication Skills
    19. The health professional works effectively with others as a member or leader of a health care team or other professional group.

  • Professionalism
    20. Respect, compassion, and integrity; a responsiveness to the needs of patients and society that supercedes self-interest; accountability to patients, society, and the profession; and a commitment to excellence and on-going professional development are demonstrated.


    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa Children’s Hospital