title: Pretreatment prediction of the outcome of response-guided peginterferon-α and ribavirin therapy for chronic hepatitis C.
abstract: OBJECTIVE
  The accuracy for predicting virological outcomes of peginterferon-α and ribavirin therapy in patients with chronic hepatitis C is limited to approximately 80%, even with IL28B genotyping. Our in vitro study revealed that the numbers of (TA) dinucleotide repeats [(TA)n] of rs72258881, which is located in the promoter region of IL28B gene, might regulate IL28B transcription. We aimed to evaluate the usefulness of these host factors for predicting virological outcomes of this therapy in response-guided clinical settings.
  
  
  METHODS
  A nationwide, multi-center prospective study in Japan determined IL28B (rs8099917) genotype, (TA)n of rs72258881, and amino acid substitutions of hepatitis C virus and used these for multivariate analysis together with other parameters at pretreatment.
  
  
  RESULTS
  After enrolling 215 patients with genotype 1 and high viral load from 23 hospitals between October 2009 and February 2011, intent-to-treat analysis identified 202 patients in whom the final virological outcomes could be determined. Non-virological response by non-TT genotype was predicted with 79.7% accuracy. When combined with the (TA)n, the incidences of virological response tended to be higher in the longer (TA)n group, regardless of rs8099917 genotype. Multivariate logistic regression analysis revealed that rs8099917 non-TT genotype (P < 0.001), shorter (TA)n (P = 0.011), mutation of amino acid 70 in the virus core region (P = 0.029), and lower levels of serum albumin (P = 0.036) were independently associated with non-virological response.
  
  
  CONCLUSIONS
  IL28B genotype and (TA)n of rs72258881 may independently affect virological outcomes of peginterferon-α and ribavirin as host factors, even in response-guided therapy.
authors.affiliation: The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Chiba, Japan.
authors.forename: Naohiko
authors.initials: N
authors.lastname: Masaki
authors.forename: Masaya
authors.initials: M
authors.lastname: Sugiyama
authors.forename: Noritomo
authors.initials: N
authors.lastname: Shimada
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakamuta
authors.forename: Namiki
authors.initials: N
authors.lastname: Izumi
authors.forename: Sumio
authors.initials: S
authors.lastname: Watanabe
authors.forename: Akihito
authors.initials: A
authors.lastname: Tsubota
authors.forename: Masafumi
authors.initials: M
authors.lastname: Komatsu
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Masaki
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Enomoto
authors.forename: Masashi
authors.initials: M
authors.lastname: Yoneda
authors.forename: Kazumoto
authors.initials: K
authors.lastname: Murata
authors.forename: Kiyoaki
authors.initials: K
authors.lastname: Ito
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Koike
authors.forename: Masashi
authors.initials: M
authors.lastname: Mizokami
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D005260:Female; D005544:Forecasting; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D007372:Interferons; D007378:Interleukins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011994:Recombinant Proteins / Q000008:administration & dosage; D012254:Ribavirin / Q000008:administration & dosage*; D016896:Treatment Outcome; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a
keywords: (TA) dinucleotide repeat; IL28B; chronic hepatitis C; response-guided therapy