title: Interferon-stimulated gene expression and hepatitis C viral dynamics during different interferon regimens.
abstract: OBJECTIVE
  To address the molecular mechanism for enhanced antiviral efficacy associated with a frequent dosing of interferon (IFN)-beta.
  
  
  METHODS
  Serum hepatitis C viral (HCV) dynamics, double-stranded RNA-activated protein kinase (PKR) mRNA and MxA mRNA levels in peripheral blood mononuclear cells (PBMC) were analyzed serially in 140 patients who were randomly assigned to a twice daily (3 MU bid) or once daily (6 MU qd) administration group.
  
  
  RESULTS
  In twice daily group, the rate of HCV decline during the second phase was 2-fold greater than in the once daily group (P=0.04). Peak PKR and MxA gene expression levels in the first phase (observed 4 h after a single administration) were 2-fold higher in the once daily group. However, the expression in the second phase was maintained at a significantly higher level in the twice daily group. Initial and peak expression levels were related to initial viral load. Basal expressions in PBMC were significantly correlated with those in the liver tissue (PKR, r=0.81; MxA, r=0.75, respectively, P<0.0001).
  
  
  CONCLUSIONS
  Our data suggest that elimination of HCV-infected cells is enhanced by twice daily dosing of IFN-beta, and that this enhanced effect is associated with a higher intracellular expression of PKR and MxA during the second phase.
authors.affiliation: Division of Gastroenterology and Hepatology, Musashino Red Cross Hospital, 1-26-1 Kyonan-cho, Musashino-shi, Tokyo 180-8610, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Asahina
authors.forename: Namiki
authors.initials: N
authors.lastname: Izumi
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Uchihara
authors.forename: Osamu
authors.initials: O
authors.lastname: Noguchi
authors.forename: Yuki
authors.initials: Y
authors.lastname: Nishimura
authors.forename: Kazunari
authors.initials: K
authors.lastname: Inoue
authors.forename: Ken
authors.initials: K
authors.lastname: Ueda
authors.forename: Kaoru
authors.initials: K
authors.lastname: Tsuchiya
authors.forename: Kosei
authors.initials: K
authors.lastname: Hamano
authors.forename: Jun
authors.initials: J
authors.lastname: Itakura
authors.forename: Shozo
authors.initials: S
authors.lastname: Miyake
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects*; D016174:Hepacivirus / Q000187:drug effects*; D006526:Hepatitis C / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D016899:Interferon-beta / Q000008:administration & dosage*; D007425:Intracellular Membranes / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D064547:Myxovirus Resistance Proteins; D012333:RNA, Messenger / Q000097:blood; D019562:Viral Load; D019892:eIF-2 Kinase / Q000235:genetics
chemical_list: D000998:Antiviral Agents; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D012333:RNA, Messenger; D016899:Interferon-beta; D019892:eIF-2 Kinase; D019204:GTP-Binding Proteins