摘要
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.
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 CD28CD27 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.
关键词
爱泼斯坦病毒
慢性肝炎
病毒感染
治疗
Chronic hepatitis
Epstein-Barr
Epstein-Barr virus-specific CD8＋ T cell
