title: Up-regulation of IL-18 by interferon alpha-2b/ribavirin combination therapy induces an anti-viral effect in patients with chronic hepatitis C.
abstract: OBJECTIVE
  Recent large prospective trials demonstrated that the combination therapy of interferon (IFN)-alpha/ribavirin significantly increased a sustained virological response rate in patients with chronic hepatitis C. However, the potential mechanism of ribavirin is not clear.
  
  
  METHODS
  Serum interleukin (IL)-18 and HCV-RNA titer were determined before and 2 weeks after administration in patients with chronic hepatitis C, who were treated with ribavirin in combination with IFN-alpha2b (combination group), and with IFN-alpha2b alone (monotherapy group).
  
  
  RESULTS
  All HCV patients were genotype 1b. In the combination group, the decline of HCV-RNA level by treatment highly correlated with the IL-18 ratio (serum IL-18 level 2 weeks after administration/serum IL-18 level before administration). Similarly, the HCV-RNA level 2 weeks after administration inversely correlated with the IL-18 ratio. In contrast, the IL-18 ratio in the monotherapy group was lower. Furthermore, the decline of HCV-RNA level did not correlate with the IL-18 ratio in the monotherapy group.
  
  
  CONCLUSIONS
  This study suggests that ribavirin may contribute to the antiviral effect through up-regulation of IL-18 in combination with IFN in patients with chronic hepatitis C.
authors.affiliation: First Department of Internal Medicine, Mie University School of Medicine, Tsu, Mie, Japan. atarum@clin.medic.mie-u.ac.jp
authors.forename: Kazumoto
authors.initials: K
authors.lastname: Murata
authors.forename: Norihiko
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kawakita
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Saito
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yamanaka
authors.forename: Kazushi
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Katsuya
authors.initials: K
authors.lastname: Shiraki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakano
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Tameda
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D020382:Interleukin-18 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D020382:Interleukin-18; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin