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 ~ Introduction
 ~ Case Report
 ~ Discussion
 ~  References

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  Table of Contents  
Year : 2018  |  Volume : 36  |  Issue : 1  |  Page : 143-144

Acute hepatitis due to Epstein–Barr virus with cross-reacting antibodies to cytomegalovirus

1 Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Maltepe University, Istanbul, Turkey
2 Department of Infectious Diseases and Clinical Microbiology, Bakirkoy Dr. Sadi Konuk Education and Research Hospital, Istanbul, Turkey
3 Department of Internal Medicine, Faculty of Medicine, Maltepe University, Istanbul, Turkey
4 Department of Emergency Medicine, Faculty of Medicine, Maltepe University, Istanbul, Turkey

Date of Web Publication2-May-2018

Correspondence Address:
Dr. Asli Karadeniz
Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Maltepe University, Feyzullah Road No: 39, Maltepe 34843, Istanbul
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijmm.IJMM_17_378

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 ~ Abstract 

Epstein–Barr virus (EBV) is the cause of systemic infection known as infectious mononucleosis with classic presentation of fever, oropharyngitis and lymphadenitis. EBV rarely causes acute hepatitis. In this report, we present a 19-year-old patient presented with nausea, fatigue and jaundice. Her physical examination and laboratory tests revealed the diagnosis as acute hepatitis due to EBV with cross-reacting antibodies to cytomegalovirus.

Keywords: Acute hepatitis, cytomegalovirus, Epstein–Barr virus

How to cite this article:
Karadeniz A, Yesilbag Z, Kaya F&, Akgün FS. Acute hepatitis due to Epstein–Barr virus with cross-reacting antibodies to cytomegalovirus. Indian J Med Microbiol 2018;36:143-4

How to cite this URL:
Karadeniz A, Yesilbag Z, Kaya F&, Akgün FS. Acute hepatitis due to Epstein–Barr virus with cross-reacting antibodies to cytomegalovirus. Indian J Med Microbiol [serial online] 2018 [cited 2021 Jan 25];36:143-4. Available from:

 ~ Introduction Top

Epstein–Barr virus (EBV) is a member of the herpesvirus family and the causal agent of infectious mononucleosis (IM) which presents with fever, sore throat and lymphadenopathy.[1],[2] Transmission occurs mainly through nasopharyngeal secretion and through close contact.[3],[4] Most primary infections occur during childhood and EBV infects up to 90% of population by the age of 20 years.[3],[4],[5] EBV can cause mild or severe systemic infections and infrequently causes hepatitis and jaundice which can rarely progress to liver failure.[1] The present report describes acute hepatitis due to EBV.

 ~ Case Report Top

A 19-year-old previously healthy female presented with nausea, fatigue, loss of appetite and dark urine for a week. Her physical examination disclosed jaundice of sclera and skin, hepatomegaly, tender liver extending 1 cm below the right costal margin and no splenomegaly. There were no findings of tonsillitis, pharyngitis, lymphadenopathy or other systemic symptoms. The laboratory studies revealed increased transaminases; aspartate aminotransferase (AST) – 256 U/L (normal range [NR]: 10–37 U/L), alanine aminotransferase (ALT) – 367 U/L (NR: 10–40 U/L), hyperbilirubinaemia (total bilirubin 5.6 mg/dl and direct bilirubin 4.6 mg/dl), increased gamma-glutamyl transpeptidase (GGT) – 259 U/L (NR: 5–55 U/L) and alkaline phosphatase (ALP) – 286 U/L (NR: 50–136 U/L). The haemogram revealed a haemoglobin level of 13.3 g/dl (NR: 12–17 g/dl), total leucocyte count of 7300/mm 3 (36% polymorphonuclear cells, 52% lymphocytes and 11% monocytes) and platelet count of 342,000/mm 3. Atypical lymphocytes (>10%) were present on peripheral blood smear. Prothrombin time-international normalized ratio was normal. Urine urobilinogen was increased. Serological markers for common hepatotropic viruses such as hepatitis A, B, C, E viruses (hepatitis B virus surface antigen, anti-hepatitis B core immunoglobulin M (IgM), anti-hepatitis C virus, anti-hepatitis A virus IgM and anti-hepatitis E virus IgM) were negative. Markers for autoimmune hepatitis, serologies for human immunodeficiency virus and brucella were also negative. The tests for cytomegalovirus (CMV) and EBV were performed. Serology both serum IgM and IgG antibodies against CMV (Architect System, Abbott Diagnostics) and Epstein–Barr viral capsid antigen (VCA) were positive. Epstein–Barr nuclear antigen (EBNA) IgG was negative (immunoblotting assay, Euroimmun, Germany). Abdominal ultrasonography showed hepatomegaly without ascites or splenomegaly. In the meantime, EBV-DNA polymerase chain reaction (PCR), tested for confirmation diagnosis, was positive in patient's plasma sample. After 5 days, the clinical course improved and laboratory findings (AST, ALT, ALP, GGT and bilirubin levels) began to decrease, and after 3 weeks, the patient was asymptomatic except for mild weakness and the laboratory findings were normal.

 ~ Discussion Top

There are a lot of viruses which can cause acute hepatitis. EBV is an uncommon aetiologic agent in acute viral hepatitis of adults.[2] EBV causes IM which presents with symptoms of fever, diphtheroid angina, lymph node swelling and hepatosplenomegaly.[5] Hepatitis due to EBV is generally seen as a complication of IM, but EBV hepatitis and jaundice have been rarely described in patients without systemic disease.[1] Serum transaminases are elevated up to two or three times the upper limit of normal in most cases in primary EBV infections.[5],[6] Our patient was presented as acute hepatitis with elevated transaminases more than 5-fold the normal levels and she had jaundice and hepatomegaly without splenomegaly. Asymptomatic, self-limited liver involvement with enzyme abnormalities is found in 80%–90% of patients with IM. Hepatomegaly occurs in approximately 10% of the patients, and jaundice occurs in only 5%–6% of patients.[3],[4],[6],[7] Jaundice has also been detected more frequently in people aged 35 years or older. Increased bilirubin levels have been reported in up to 35% of the patients with IM but are rarely seen without splenomegaly.[8]

Acute EBV infection is usually diagnosed by serology. VCA IgG, VCA IgM and EBNA-1 IgG are essential parameters for diagnosis. EBV VCA IgM appears early and disappears within 4–6 weeks of the infection. EBV VCA IgG and EBNA IgG indicate past or latent infection.[9] Acute EBV infection is confirmed by positive VCA IgM and VCA IgG and absent EBNA antibodies while recent infection (in 3–12 months) is associated with positive VCA IgG and EBNA antibodies and negative VCA IgM.[3]

Serologic tests for CMV and EBV (CMV IgM, EBV VCA IgM and IgG) were positive for our patient, and EBNA IgG was negative. Due to the antigenic cross-reactivity with other herpesviruses,[5],[10] molecular techniques for detection of EBV DNA are required.[5] For this purpose, quantitative real-time PCR can be done on blood, plasma or tissue samples for confirmation of acute EBV infection.[5],[11] EBV-DNA PCR was positive in our patient's plasma sample, and CMV-PCR was negative which showed that positive test for CMV serology was false-positive result due to cross-reacting antibodies. Our patient improved with symptomatic therapy.

Primary EBV infection rarely causes acute hepatitis which is usually mild and self-limited,[3],[5] and treatment is supportive.[3] EBV should be considered in differentiating diagnosis for acute hepatitis.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

 ~ References Top

Mellinger JL, Rossaro L, Naugler WE, Nadig SN, Appelman H, Lee WM, et al. Epstein-Barr virus (EBV) related acute liver failure: A case series from the US acute liver failure study group. Dig Dis Sci 2014;59:1630-7.  Back to cited text no. 1
Park MJ, Chung IK, Park YD, Chung YJ, Lee HC, Cho HJ, et al. A case of cholestatic hepatitis induced by Epstein-Barr virus infection. Korean J Hepatol 2006;12:237-42.  Back to cited text no. 2
Kang MJ, Kim TH, Shim KN, Jung SA, Cho MS, Yoo K, et al. Infectious mononucleosis hepatitis in young adults: Two case reports. Korean J Intern Med 2009;24:381-7.  Back to cited text no. 3
Kofteridis DP, Koulentaki M, Valachis A, Christofaki M, Mazokopakis E, Papazoglou G, et al. Epstein Barr virus hepatitis. Eur J Intern Med 2011;22:73-6.  Back to cited text no. 4
Gupta E, Bhatia V, Choudhary A, Rastogi A, Gupta NL. Epstein-Barr virus associated acute hepatitis with cross-reacting antibodies to other herpes viruses in immunocompetent patients: Report of two cases. J Med Virol 2013;85:519-23.  Back to cited text no. 5
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;4:469-76.  Back to cited text no. 6
Crum NF. Epstein Barr virus hepatitis: Case series and review. South Med J 2006;99:544-7.  Back to cited text no. 7
Salva I, Silva IV, Cunha F. Epstein-Barr virus-associated cholestatic hepatitis. BMJ Case Rep 2013;2013. pii: bcr2013202213.  Back to cited text no. 8
Hess RD. Routine Epstein-Barr virus diagnostics from the laboratory perspective: Still challenging after 35 years. J Clin Microbiol 2004;42:3381-7.  Back to cited text no. 9
Balachandran N, Oba DE, Hutt-Fletcher LM. Antigenic cross-reactions among herpes simplex virus types 1 and 2, Epstein-Barr virus, and cytomegalovirus. J Virol 1987;61:1125-35.  Back to cited text no. 10
Odumade OA, Hogquist KA, Balfour HH Jr. Progress and problems in understanding and managing primary Epstein-Barr virus infections. Clin Microbiol Rev 2011;24:193-209.  Back to cited text no. 11


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