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Telbivudine therapy may shape CD4+ T-cell response to prevent liver fibrosis in patients with chronic hepatitis B



Background & Aims

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.


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).


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+CD25highFoxp3+) 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.


Telbivudine might slow down HBV-related liver fibrosis progression by restoring CD4+ T-cell responses against HBV.