title: Telbivudine therapy may shape CD4(+) T-cell response to prevent liver fibrosis in patients with chronic hepatitis B.
abstract: OBJECTIVE
  Nucleos(t)ide analogues (NAs) can indirectly restore host immunity against hepatitis B virus (HBV) by inhibiting virus replication. We aimed to investigate whether telbivudine could prevent HBV-related fibrosis progression by their influence on CD4(+) T-cell response.
  
  
  METHODS
  Thirty-six HBeAg-positive patients with chronic hepatitis B (CHB) were enrolled for 52-week telbivudine monotherapy and were followed at treatment week (TW)-0, 4, 12, 24 and 52. By TW-52, the patients were classified into a complete-response group (CR, n = 10) with both negative HBV-DNA and HBeAg, or a part-response group (PR, n = 11) only with negative DNA, or a non-response group (NR, n = 15) still with positive DNA. The peripheral blood mononuclear cells (PBMCs) were prepared for further flow cytometric and real-time PCR analyses, and also for the in vitro experiments with primary hepatic stellate cells (HSCs).
  
  
  RESULTS
  Peripherally, all chronic HBV-infected subjects showed the involvement of CD4(+) T-cell responses, among whom the inactive carriers (IC) had Th1 (CD4(+) IFNγ(+) ) dominated, CHB had Th17 (CD4(+) IL-17(+) ) dominated, while the immune tolerant (IT) subjects had Treg (CD4(+) CD25(high) Foxp3(+) ) dominated. Besides, we found the therapeutic responses to telbivudine were especially associated with up-regulation of Th1 and Th17, and down-regulation of Treg. Furthermore, compared to CD4(+) cells from CR, those from NR could in vitro significantly exacerbate cell activation, proliferation and cytokine production of HSCs, which were partly mediated by IL-4 and TGF-β1.
  
  
  CONCLUSIONS
  Telbivudine might slow down HBV-related liver fibrosis progression by restoring CD4(+) T-cell responses against HBV.
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, China; Department of Gastroenterology, Tongji Hospital, Tongji University, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Minglei
authors.initials: M
authors.lastname: Jia
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.forename: Weimin
authors.initials: W
authors.lastname: She
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.forename: Jiyao
authors.initials: J
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
mesh_terms: D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000097:blood; D004279:DNA, Viral / Q000097:blood; D015536:Down-Regulation; D005260:Female; D055166:Hepatic Stellate Cells / Q000276:immunology; D006513:Hepatitis B e Antigens / Q000097:blood; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D008103:Liver Cirrhosis / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D000077712:Telbivudine; D013936:Thymidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D053773:Transforming Growth Factor beta1 / Q000097:blood; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D016207:Cytokines; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D053773:Transforming Growth Factor beta1; D000077712:Telbivudine; D013936:Thymidine
keywords: CD4+ T subsets; chronic hepatitis B; hepatic stellate cells; liver fibrosis; telbivudine