title: Peripheral blood mononuclear cells microRNA predicts treatment outcome of hepatitis C virus genotype 1 infection.
abstract: BACKGROUND
  Chronic hepatitis C virus (HCV) infection has been associated with induction of microRNAs (miRNAs) in peripheral blood mononuclear cells (PBMC). We aimed to evaluate the role of PBMC-miRNAs in the treatment outcome to antiviral therapy for HCV genotype 1 (HCV-1) patients.
  
  
  METHODS
  Treatment-naive chronic HCV-1 patients, including 13 in screening phase and 48 in validation phase, were treated with 48weeks of peginterferon/ribavirin. The primary end-point was the achievement of a sustained virological response (SVR, HCV RNA undetectable during 24weeks post-treatment follow-up). Expression profiling of PBMC-miRNAs was performed by quantitative PCR-based array in typical responders and null-responders. Then candidate PBMC-miRNAs were validated by quantitative PCR in an independent validation set.
  
  
  RESULTS
  PBMC-miR-125b was significantly predictive of an SVR, with expression levels of 5.28-fold lower in sustained responders versus null-responders (p=0.0163). In multivariate analysis, PBMC-miR-125b was significantly associated with the achievement of SVR (per 2-fold decrease, odds ratio/95% confidence interval (OR/CI): 2.07/1.14-6.31) independent of sex, age and interleukin-28B genotype. In patients who did not achieve a rapid virological response (RVR, undetectable HCV RNA at treatment week 4), PBMC-miR-125b was the only predictive factor of an SVR (per 2-fold decrease, OR/CI: 2.07/1.14-6.31). However, the circulating and hepatic miR-125b did not show significant difference between responders and non-responders.
  
  
  CONCLUSIONS
  PBMC-miR-125b expression levels were inversely related to the achievement of an SVR in HCV-1 patients, independent of interleukin-28B genotype, and was the single predictor of SVR in non-RVR patients.
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Medical Research, Kaohsiung Medical University Hospital, Taiwan.
authors.forename: Edward
authors.initials: E
authors.lastname: Hsi
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Occupational Medicine, Kaohsiung Municipal Ta-Tung Hospital, Taiwan.
authors.forename: Chung-Feng
authors.initials: CF
authors.lastname: Huang
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Chia-Yen
authors.initials: CY
authors.lastname: Dai
authors.affiliation: Department of Medical Research, Kaohsiung Medical University Hospital, Taiwan; Department of Medical Genetics, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Suh-Hang Hank
authors.initials: SH
authors.lastname: Juo
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Wen-Wen
authors.initials: WW
authors.lastname: Chou
authors.affiliation: Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Jee-Fu
authors.initials: JF
authors.lastname: Huang
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Ming-Lun
authors.initials: ML
authors.lastname: Yeh
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Zu-Yau
authors.initials: ZY
authors.lastname: Lin
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Shinn-Cherng
authors.initials: SC
authors.lastname: Chen
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Liang-Yen
authors.initials: LY
authors.lastname: Wang
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: waloch@kmu.edu.tw.
authors.forename: Wan-Long
authors.initials: WL
authors.lastname: Chuang
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: fish6069@gmail.com.
authors.forename: Ming-Lung
authors.initials: ML
authors.lastname: Yu
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D015415:Biomarkers; D005260:Female; D020869:Gene Expression Profiling; D005838:Genotype; D016174:Hepacivirus / Q000145:classification* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000821:virology; D008297:Male; D035683:MicroRNAs / Q000032:analysis* / Q000235:genetics; D008875:Middle Aged; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D016898:Interferon-alpha; D035683:MicroRNAs; D012254:Ribavirin
keywords: HCV; IL28B; MicroRNA; PBMC; SVR; miR-125b