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. 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^highFoxp3⁺) 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. [ABSTRACT FROM AUTHOR]