- 作者：Anthony T. Tan ; Long Truong Hoang ; Daniel Chin ; Erik Rasmussen ; Uri Lopatin ; Stefan Hart ; Hans Bitter ; Tom Chu ; Lore Gruenbaum ; Palani Ravindran ; Hua Zhong ; Ed Gane ; Seng Gee Lim ; Wan Cheng Chow ; Pei-Jer Chen ; Rosemary Petric ; Antonio Bertoletti ; Martin Lloyd Hibberd
- 关键词：Chronic HBV ; PegIFNa ; Tenofovir
- 刊名：Journal of Hepatology
- 出版年：January, 2014
- 年：2014
- 卷：60
- 期：1
- 页码：54-61
- 全文大小：990 K
Background & Aims
The interaction between HBV replication and immune modulatory effects mediated by IFN伪 therapy is not well understood. We characterized the impact of HBV DNA replication on the early IFN伪-induced immunomodulatory mechanisms.Methods
We interrogated the transcriptional, serum cytokine/chemokine and cellular immune profiles of 28 patients with HBeAg+ chronic HBV infection (CHB) randomly assigned to one of 4 treatment cohorts (untreated n = 5, weekly dosing of 360 渭g Pegasys庐 [PegIFN伪] n = 11, daily dose of 300 mg Viread庐 [tenofovir disoproxil fumarate, TDF] n = 6, or a combination of both n = 6). Samples were characterized at multiple early time points through day 14 of therapy, after which all patients were given standard of care (180 渭g Pegasys庐 injected subcutaneously, weekly).
Results
PegIFN伪 induced a distinct and rapid up-regulation of IFN signaling pathway that coincided with increase detection of distinct serum cytokines/chemokines (IL-15, IL-6, and CXCL-10) and the up-regulation of the frequency of proliferating NK and activated total CD8+ T cells. IFN伪 treatment alone did not result in rapid decay of HBV replication and was not able to restore the defective HBV-specific T cell response present in CHB patients. In addition, the IFN伪 immune-stimulatory effects diminished after the first dose, but this refractory effect was reduced in patients where HBV replication was simultaneously inhibited with TDF.
Conclusions
We present here the first comprehensive description of the early effects of IFN伪 treatment on immune and viral biomarkers in HBeAg+ CHB patients. Our results show that PegIFN伪-induced innate immune activation directly benefits from the suppression of HBV replication.