title: Liver interleukin-8 messenger RNA expression and interferon sensitivity-determining region mutations relate to treatment response in hepatitis C 1b.
abstract: BACKGROUND
  In vitro study has shown that mechanisms for inhibiting interferon (IFN)-α antiviral action by non-structural 5A protein include interaction with IFN-induced RNA-dependent protein kinase and induction of interleukin (IL)-8 expression. Mutations in the non-structural 5A IFN sensitivity-determining region (ISDR) were reported to correlate with sustained virological response (SVR). IL-8 is associated with the inhibition of IFN-α action. We investigated whether pretreatment ISDR mutations and hepatic IL-8 messenger RNA (mRNA) expression had an effect on the SVR rate under combination therapy.
  
  
  METHODS
  A total of 53 HCV-1b patients who completed 24 weeks of pegylated-IFN-α2b plus ribavirin, a 24-week follow-up and had enough tissue specimens were enrolled. Liver biopsy was performed within 6 months before antiviral therapy. Hepatic IL-8 mRNA expression was measured by real-time reverse transcriptase PCR.
  
  
  RESULTS
  Of 53 patients, 30 exhibited SVR. Multivariate analysis revealed that hepatic IL-8 mRNA expression <1.5×10(-4) (OR 6.66, 95% CI 1.77-25.05) and ISDR mutations ≥4 (OR 12.20, 95% CI 1.23-125.00) were independent predictors of SVR. Fibrosis scores and alanine aminotransferase levels were predictive of hepatic IL-8 mRNA expression by multiple linear regression analysis (r(2)=0.204).
  
  
  CONCLUSIONS
  SVR to combination therapy in hepatitis C 1b patients was associated with down-regulated hepatic IL-8 mRNA expression and ISDR mutations. Fibrosis scores and alanine aminotransferase levels were predictive of hepatic IL-8 mRNA expression.
authors: Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan. chmolee@ms15.hinet.net
authors: Chuan-Mo
authors: CM
authors: Lee
authors: Yi-Hao
authors: YH
authors: Yen
authors: Chao-Hung
authors: CH
authors: Hung
authors: Sheng-Nan
authors: SN
authors: Lu
authors: Jing-Houng
authors: JH
authors: Wang
authors: Jyh-Chwan
authors: JC
authors: Wang
authors: Chien-Hung
authors: CH
authors: Chen
authors: Kwong-Ming
authors: KM
authors: Kee
authors: Tsung-Hui
authors: TH
authors: Hu
authors: Chi-Sin
authors: CS
authors: Changchien
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D005786:Gene Expression Regulation; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D016209:Interleukin-8 / Q000235:genetics*; D008099:Liver / Q000378:metabolism / Q000821:virology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D016896:Treatment Outcome; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D007372:Interferons; D016209:Interleukin-8; D012333:RNA, Messenger; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase