Chronic Epstein-Barr virus-related hepatitis in immunocompetent patients.
OBJECTIVE
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-gamma.


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-gamma 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.


CONCLUSIONS
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.
Petrova
Mihaela
M
Clinic of Gastroenterology, Medical Institute Ministry of Interior, Skobelev 79, Sofia 1606, Bulgaria. mpetrova@gmail.com
Muhtarova
Maria
M
Nikolova
Maria
M
Magaev
Svetoslav
S
Taskov
Hristo
H
Nikolovska
Diana
D
Krastev
Zahariy
Z
D000328:Adult; D018106:CD28 Antigens / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D016022:Case-Control Studies; D020031:Epstein-Barr Virus Infections / Q000097:blood / Q000150:complications* / Q000276:immunology / Q000473:pathology; D005260:Female; D006521:Hepatitis, Chronic / Q000097:blood / Q000209:etiology* / Q000473:pathology / Q000821:virology; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D016867:Immunocompromised Host / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000097:blood; D008099:Liver / Q000276:immunology / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D000637:Transaminases / Q000097:blood; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000097:blood
D018106:CD28 Antigens; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D000637:Transaminases; D017493:Leukocyte Common Antigens