title: Effect of telbivudine therapy on the cellular immune response in chronic hepatitis B.
abstract: Weak T-cell reactivity to the hepatitis B virus (HBV) is believed to be the dominant cause of chronic HBV infection. Several lines of experimental evidence suggest that treatment with telbivudine increases the rate of HBV e antigen (HBeAg) loss, undetectable HBV DNA, and normalization of serum alanine aminotransferase (ALT) in chronic hepatitis B patients (CHB). However, it is still unclear how early antiviral therapy affects cellular immune responses during sustained telbivudine treatment. In order to investigate this issue, we measured detailed prospective clinical, virological, and biochemical parameters, and we examined the frequency of T cell subgroups as well as the ability of peripheral blood mononuclear cells (PBMC) to respond to stimuli at five protocol time points for 51 CHB patients who received telbivudine therapy for one year. The preliminary data from this study revealed that effective-treated patients showed an increased frequency of peripheral blood CD4(+)T lymphocytes, an augmented proliferative response of HBV-specific T-cells to the hepatitis B core antigen (HBcAg), and the induction of cytokines, such as interferon gamma (IFN-γ), tumour necrosis factor alpha (TNF-α) release at the site of infection compared to non-responsive patients. Enhanced HBV-specific T-cell reactivity to telbivudine therapy, which peaked at treatment week 12, was confined to a subgroup of effective-treated patients who achieved greater viral suppression.
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, Qingchun Road, Hangzhou, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Xuefen
authors.initials: X
authors.lastname: Li
authors.forename: Bo
authors.initials: B
authors.lastname: Ye
authors.forename: Xianzhi
authors.initials: X
authors.lastname: Yang
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Baode
authors.initials: B
authors.lastname: Chen
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Pan
authors.forename: Hongcui
authors.initials: H
authors.lastname: Cao
authors.forename: Lanjuan
authors.initials: L
authors.lastname: Li
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004279:DNA, Viral / Q000097:blood; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D006512:Hepatitis B Core Antigens / Q000097:blood / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D008099:Liver / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D009705:Nucleosides / Q000494:pharmacology* / Q000627:therapeutic use; D011744:Pyrimidinones / Q000494:pharmacology* / Q000627:therapeutic use; D000077712:Telbivudine; D013936:Thymidine / Q000031:analogs & derivatives; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D016207:Cytokines; D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D009705:Nucleosides; D011744:Pyrimidinones; D000077712:Telbivudine; D000410:Alanine Transaminase; D013936:Thymidine