title: Dynamics of PBMC gene expression in hepatitis C virus genotype 1-infected patients during combined peginterferon/ribavirin therapy.
abstract: Hepatitis C virus (HCV) can replicate in peripheral blood mononuclear cells (PBMCs), which can produce interferon to defend against virus infection. We hypothesized that dynamic gene expression in PBMCs might impact the treatment efficacy of peginterferon/ribavirin in HCV patients. PBMCs were collected at baseline, 1st week and 4th week of treatment from 27 chronic HCV-1 patients with 48-week peginterferon/ribavirin therapy (screening dataset n = 7; validation dataset n = 20). A sustained virologic response (SVR) was defined as undetectable HCV RNA throughout the 24 weeks after end-of-treatment. A complete early virologic response (cEVR) was defined as negative HCV RNA at treatment week 12. Forty-three differentially expressed genes identified by Affymetrix microarray were validated by quantitative polymerase chain reaction. Thirteen genes at week 1 and 24 genes at week 4 were upregulated in the SVR group compared with the non-SVR group. We selected 8 target genes (RSAD2, LOC26010, HERC5, HERC6, IFI44, SERPING1, IFITM3, and DDX60) at week 1 as the major components of the predictive model. This predictive model reliably stratified the responders and non-responders at week 1 (AUC = 0.89, p = 0.007 for SVR; AUC = 0.95, p = 0.003 for cEVR), especially among patients carrying the IL28B rs8099917 TT genotype (AUC = 0.89, p = 0.02 for SVR; AUC = 1.0, p = 0.008 for cEVR). The performance of this predictive model was superior to traditional predictors, including the rapid virologic response, viral load and IL28B genotype.
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Ming-Ying
authors.initials: MY
authors.lastname: Lu
authors.affiliation: Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Ching-I
authors.initials: CI
authors.lastname: Huang
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Ming-Yen
authors.initials: MY
authors.lastname: Hsieh
authors.affiliation: Department of Genome Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Tusty-Juan
authors.initials: TJ
authors.lastname: Hsieh
authors.affiliation: Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Edward
authors.initials: E
authors.lastname: Hsi
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Pei-Chien
authors.initials: PC
authors.lastname: Tsai
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Yi-Shan
authors.initials: YS
authors.lastname: Tsai
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Ching-Chih
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Meng-Hsuan
authors.initials: MH
authors.lastname: Hsieh
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Po-Cheng
authors.initials: PC
authors.lastname: Liang
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Yi-Hung
authors.initials: YH
authors.lastname: Lin
authors.affiliation: Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Nai-Jen
authors.initials: NJ
authors.lastname: Hou
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan.|Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Ming-Lun
authors.initials: ML
authors.lastname: Yeh
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Occupational Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chung-Feng
authors.initials: CF
authors.lastname: Huang
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Zu-Yau
authors.initials: ZY
authors.lastname: Lin
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Shinn-Cherng
authors.initials: SC
authors.lastname: Chen
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Jee-Fu
authors.initials: JF
authors.lastname: Huang
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Wan-Long
authors.initials: WL
authors.lastname: Chuang
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan.|Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chia-Yen
authors.initials: CY
authors.lastname: Dai
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan.|Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.|Liver Center, Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Ming-Lung
authors.initials: ML
authors.lastname: Yu
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D012254:Ribavirin / Q000627:therapeutic use*; D017423:Sequence Analysis, RNA; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; C571406:PEG-IFN-SA; D011092:Polyethylene Glycols; D012254:Ribavirin
keywords: hepatitis C; interferon; sustained virologic response