title: Peripheral blood toll-like receptor 4 correlates with rapid virological response to pegylated-interferon and ribavirin therapy in hepatitis C genotype 1 patients.
abstract: BACKGROUND
  Toll-like receptors (TLRs) are effectors of the innate immune system that are able to recognize hepatitis C virus (HCV) and give rise to an immune response. Failure of interferon (IFN)-α-based treatment is related to host immunity. Therefore, we sought to study the clinical importance of TLRs in HCV genotype 1 patients who received pegylated IFN (PEG-IFN) plus ribavirin (RBV) therapy.
  
  
  METHODS
  We enrolled 79 treatment-naïve patients with HCV genotype 1. Patients completed a 24- to 48-week course of response-guided therapy. Peripheral blood monocyte (PBMC) expression of mRNA for TLRs 2, 3, 4, 7, and 9 was quantified by real-time PCR before therapy. TLR mRNA expression is shown as a log ratio relative to GAPDH mRNA (log 2 (-(∆Ct))).
  
  
  RESULTS
  Forty-five patients (57.0 %) showed a rapid virological response (RVR). Univariate analysis revealed that TLR 2, 3, 4, 7, and 9 were significantly lower in the RVR group than in the non-RVR group (P = 0.001, 0.014, < 0.001, 0.008, and 0.001, respectively). Multivariate analysis revealed that TLR 4 < -2 log (OR: 7.17, 95 % CI: 1.70-30.34, P = 0.007) was an independent predictor for RVR. In addition, levels of TLR 2, 3, 4, 7, and 9 were positively correlated with HCV viral load (P = 0.009, 0.013, < 0.001, 0.007, and 0.001, respectively).
  
  
  CONCLUSIONS
  A low level of TLR 4 mRNA in PMBCs was correlated with RVR, which indicates that TLR4 may play a critical role in HCV recognition and activation of innate immunity. TLR expression levels were correlated with HCV viral load, indicating that TLR activation upon exposure to HCV may subsequently limit HCV replication.
authors.affiliation: Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, 123 Ta Pei Road, Niao Sung Dist. 833, Kaohsiung City, Taiwan.|School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Chuan-Mo
authors.initials: CM
authors.lastname: Lee
authors.affiliation: Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, 123 Ta Pei Road, Niao Sung Dist. 833, Kaohsiung City, Taiwan.|School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Tsung-Hui
authors.initials: TH
authors.lastname: Hu
authors.affiliation: Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, 123 Ta Pei Road, Niao Sung Dist. 833, Kaohsiung City, Taiwan.|School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Sheng-Nan
authors.initials: SN
authors.lastname: Lu
authors.affiliation: Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, 123 Ta Pei Road, Niao Sung Dist. 833, Kaohsiung City, Taiwan.|School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Jing-Houng
authors.initials: JH
authors.lastname: Wang
authors.affiliation: Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, 123 Ta Pei Road, Niao Sung Dist. 833, Kaohsiung City, Taiwan.|School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Chao-Hung
authors.initials: CH
authors.lastname: Hung
authors.affiliation: Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, 123 Ta Pei Road, Niao Sung Dist. 833, Kaohsiung City, Taiwan.|School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Chien-Hung
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, 123 Ta Pei Road, Niao Sung Dist. 833, Kaohsiung City, Taiwan. cassellyen@yahoo.com.tw.|School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan. cassellyen@yahoo.com.tw.
authors.forename: Yi-Hao
authors.initials: YH
authors.lastname: Yen
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D015870:Gene Expression; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use*; D051197:Toll-Like Receptor 4 / Q000097:blood* / Q000235:genetics; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012333:RNA, Messenger; D011994:Recombinant Proteins; D051197:Toll-Like Receptor 4; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a
keywords: Hepatitis C virus; Rapid virological response; Toll-like receptor