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World J Gastroenterol. Sep 21, 2006; 12(35): 5711-5716
Published online Sep 21, 2006. doi: 10.3748/wjg.v12.i35.5711
Chronic Epstein-Barr virus-related hepatitis in immunocompetent patients
Mihaela Petrova, Maria Muhtarova, Maria Nikolova, Svetoslav Magaev, Hristo Taskov, Diana Nikolovska, Zahariy Krastev
Mihaela Petrova, Diana Nikolovska, Clinic of Gastroenterology, Medical Institute Ministry of Interior, Sofia, Bulgaria
Maria Muhtarova, Maria Nikolova, Svetoslav Magaev, Hristo Taskov, Central Laboratory of Immunology, National Centre of Infectious and Parasitic Diseases, Sofia, Bulgaria
Zahariy Krastev, Clinic of Gastroenterology, University Hopsital “St. Iv. Rilsky”, Sofia, Bulgaria
Co-first-author: Maria Muhtarova
Correspondence to: Mihaela Petrova, MD, Clinic of Gastroenterology, Medical Institute Ministry of Interior, “Skobelev” 79, Sofia 1606, Bulgaria. mpetrova@gmail.com
Telephone: +359-2-9821356 Fax: +359-2-9835201
Received: April 3, 2006
Revised: May 15, 2006
Accepted: May 25, 2006
Published online: September 21, 2006

AIM: To investigate reactivated Epstein-Barr virus (EBV) infection as a cause for chronic hepatitis.

METHODS: Patients with occasionally established elevated serum aminotransferases were studied. HIV, HBV and HCV-infections were excluded as well as any other immunosuppressive factors, metabolic or toxic disorders. EBV viral capsid antigen (VCA) IgG and IgM, EA-R and EA-D IgG and Epstein-Barr nuclear antigen (EBNA) were measured using IFA kits. Immunophenotyping of whole blood was performed by multicolor flow cytometry. CD8+ T cell responses to EBV and PHA were determined according to the intracellular expression of IFN-γ.

RESULTS: The mean alanine aminotransferase (ALT) and gamma glutamyl transpeptidase (GGTP) values exceeded twice the upper normal limit, AST/ALT ratio < 1. Serology tests showed reactivated EBV infection in all patients. Absolute number and percentages of T, B and NK cells were within the reference ranges. Fine subset analysis, in comparison to EBV+ healthy carriers, revealed a significant decrease of naive T cells (P < 0.001), accompanied by increased percentage of CD45RA- (P < 0.0001), and terminally differentiated CD28-CD27-CD8+ T cells (P < 0.01). Moderately elevated numbers of CD38 molecules on CD8+ T cells (P < 0.05) proposed a low viral burden. A significantly increased percentage of CD8+ T cells expressing IFN-γ in response to EBV and PHA stimulation was registered in patients, as compared to controls (P < 0.05). Liver biopsy specimens from 5 patients revealed nonspecific features of low-grade hepatitis.

CONCLUSION: Chronic hepatitis might be a manifestation of chronic EBV infection in the lack of detectable immune deficiency; the expansion of CD28-CD27- and increase of functional EBV-specific CD8+ T cells being the only surrogate markers of viral activity.

Keywords: Chronic hepatitis, Epstein-Barr, Epstein-Barr virus-specific CD8+ T cell