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

Abstract

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(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: Jing Li, Minglei Jia, Yun Liu, Weimin She, Lei Li, Jiyao Wang, Wei Jiang
• Journal: Liver international : official journal of the International Association for the Study of the Liver (Liver Int) Vol. 35 Issue 3 Pg. 834-45 (Mar 2015) ISSN: 1478-3231 [Electronic] United States
• PMID: 24814578 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• Antiviral Agents
• Cytokines
• DNA, Viral
• Hepatitis B e Antigens
• Transforming Growth Factor beta1
• Telbivudine
• Thymidine

Topics

• Adolescent
• Adult
• Antiviral Agents (therapeutic use)
• CD4-Positive T-Lymphocytes (immunology)
• Case-Control Studies
• Cells, Cultured
• Coculture Techniques
• Cytokines (blood)
• DNA, Viral (blood)
• Down-Regulation
• Female
• Hepatic Stellate Cells (immunology)
• Hepatitis B e Antigens (blood)
• Hepatitis B, Chronic (drug therapy)
• Humans
• Liver Cirrhosis (prevention & control)
• Male
• Middle Aged
• Real-Time Polymerase Chain Reaction
• Telbivudine
• Thymidine (analogs & derivatives, therapeutic use)
• Transforming Growth Factor beta1 (blood)
• Up-Regulation
• Young Adult