In keeping with our findings, Hashad et al. [22] and Yuki et al. [23] found that pretreatment up-regulation of hepatic TLR3 expression was a predictive factor for non-respond. selleck HCV infection could activate monocytes via TLRs pathway and elevate the expression of TLR3 as our study found, but pre-existing monocytes activation was a factor mediating reduced responses to TLR3 stimulation [42]. Thus, infection of monocytes by HCV may account for a defective response to HCV infection. Furthermore, the endogenous IFN system activation in the liver before treatment not only was ineffective in HCV clearance but also hampered further response to exogenous IFN plus RBV [37]. These reasons might explain why the level of TLR3 expressing CD14+ monocytes was lower in cEVR patients than that in non-cEVR ones, but further and expanded investigations were needed to clarify the underlying mechanisms.

Therefore, the baseline level of peripheral TLR3 expressing CD14+ monocytes might serve as a predictor of response to antiviral therapy and have a substantial impact on treatment decision-making. Conclusions In summary, the present study suggested that low peripheral TLR3 expressing CD14+ monocytes at baseline was a novel predictor for early virological response of antiviral therapy in chronic HCV-infected patients. The patients treated with interferon plus ribavirin could achieve completely early virological response through the modulation of peripheral CD4+CD25+FoxP3+ regulatory T-cells, PD-1 expressing CD4+ or CD8+ T-cells and TLR3 expressing CD14+ monocytes.

Supporting Information Checklist S1 CONSORT 2010 checklist information to report the randomized parallel-group study. The study process, reported sections and topics, checklist item numbers, content and described sections in this manuscript were described. (DOC) Click here for additional data file.(95K, doc) Protocol S1 Study protocol in English. Study design and exclusion criteria for this study was presented in English in this protocol. (DOC) Click here for additional data file.(33K, doc) Protocol S2 Study protocol in Chinese. Study design and exclusion criteria for this study was presented in Chinese in this protocol. (DOC) Click here for additional data file.(37K, doc) Acknowledgments We are grateful to all subjects who generously provided blood samples for this study. A special thanks to Prof. Qing-bao Tian, Ms.

Ying-jun Bei and Mrs. Xue-min Niu for their precious help in the statistic analysis of this manuscript. Funding Statement This study was supported by the Key Program for Science and Technology Development of Hebei Province named Study on Prevention Drug_discovery and Control of Viral Hepatitis (10276102D). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.