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. 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 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 + RESULTS: The mean alanine aminotransferase (ALT) and gamma glutamyl transpeptidase (GGTP) values ​​exceeded twice the upper normal limit, AST / ALT ratio <1. T cell responses to EBV and PHA were determined according to the intracellular expression of IFN- 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 in naive T cells (P <0.001), accompanied by an increased percentage of CD45RA- (P <0.0001), and terminally differentiated CD28-CD27- CD8 + T cells A significant increase in 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.