title: Elevated on-treatment levels of serum IFN-gamma is associated with treatment failure of peginterferon plus ribavirin therapy for chronic hepatitis C.
abstract: Chronic hepatitis C virus (HCV) infection had been associated with cytokine imbalance. Cytokine dynamics in response to peginterferon/ribavirin therapy have an impact on the treatment efficacy for HCV patients. Ninety-two treatment-naive chronic hepatitis C patients were treated with 24 or 48 weeks of peginterferon/ribavirin therapy according to their viral genotypes. Sustained virologic response (SVR) is defined as undetectable HCV RNA throughout a 24-week post-treatment follow-up period. Dynamic serum levels of the following cytokines: (1) Th1-mediated cytokines: IFN-γ, interleukin-2, and TNF-alpha; (2)Th2-mediated cytokines: interleukin-4, interleukin-5, interleukin-6, and interleukin-10 and (3)immuno-modulatory cytokines: interleukin-1β, interleukin-8, and interleukin-12 were determined by Fluorescent Bead immunoassay. Serial dynamic cytokine expression demonstrated that not only elevated IFN-γ concentrations at specific time points but also the total IFN-γ amount was strongly linked to non-response in peginterferon/ribavirin therapy. IFN-γ levels could serve as an independent predictor for SVR analyzed by multivariate logistic regression test. The accuracy of discriminating responders from non-responders was acceptable when IFN-γ cut-off levels were set at 180, 120, and 40 pg/ml at the 4th week, 12th week, and end-of-treatment of therapy, respectively. Elevated on-treatment IFN-γ concentration was significantly associated with treatment failure among interleukin-28B rs8099917TT carriers and those patients failed to achieve rapid virologic response.
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.|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.|Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Shu-Chi
authors.initials: SC
authors.lastname: Wang
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: 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.|Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.
authors.forename: Ming-Lung
authors.initials: ML
authors.lastname: Yu
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics* / Q000472:pathogenicity; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007371:Interferon-gamma / Q000097:blood*; D007372:Interferons; D007378:Interleukins / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D012254:Ribavirin / Q000008:administration & dosage / Q000009:adverse effects; D017211:Treatment Failure; D019562:Viral Load / Q000187:drug effects / Q000235:genetics; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D007371:Interferon-gamma; D007372:Interferons; D007378:Interleukins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda