title: Relationship of interferon-γ-inducible protein-10 kDa with viral response in patients with various heterogeneities of hepatitis C virus genotype-4.
abstract: BACKGROUND
  The role of serum interferon-γ-inducible protein-10 kDa (IP-10) level in the treatment of chronic hepatitis C genotype-4 (HCV-4) and its various subtypes remains unknown. We aimed to study the impact of pretreatment IP-10 levels on the sustained viral response (SVR) in HCV-4 patients (n=64) undergoing peginterferon α-2a/ribavirin therapy.
  
  
  METHODS
  Pretreatment IP-10 levels and HCV-4 subtypes (4a=48.4%, 4d=39%, others=12.5%) were measured and correlated with treatment responses. Variables significantly associated with SVR on univariate analysis were included in a multivariate logistic regression model.
  
  
  RESULTS
  Patients with SVR had lower pretreatment IP-10 levels (462.4±282.7 vs. 840.1±490.6 pg/ml; P=0.002), but the levels were not significantly different in those with a rapid (P=0.245) or an early viral response (P=0.221). IP-10 levels were similar across all subtypes. The pretreatment level was significantly lower in subtype 4d patients with SVR (465.9±349.1) compared with non-SVR patients (904.9±532.1; P<0.001), but not when compared with genotype 4a patients (564.7±288.9 vs. 658.6±374.9, respectively; P=0.330). IP-10 levels [odds ratio (OR), 0.998; 95% confidence interval (CI): 0.996-0.999; P=0.006], low viremia (OR, 8.852; 95% CI: 1.244-63.03; P=0.029), and early viral response (OR, 4.162; 95% CI: 1.023-16.94; P=0.046) were independent predictors of SVR. Receiver operating characteristic curve analysis identified a threshold IP-10 level of 359 pg/ml (area under receiver operating characteristic curve, 0.737; sensitivity, 81.8%; specificity, 45.2; positive predictive value, 43.9%; negative predictive value, 82.6%) for SVR.
  
  
  CONCLUSIONS
  Pretreatment serum IP-10 level is a predictor for SVR in HCV-4-infected patients. The baseline IP-10 level is significantly lower in responders among HCV genotype-4d patients as compared with 4a patients.
authors.affiliation: Section of Gastroenterology, Department of Medicine, King Faisal Specialist Hospital and Research Centre KFSH&RC, Riyadh 11211, Saudi Arabia.
authors.forename: Hamad I
authors.initials: HI
authors.lastname: Al-Ashgar
authors.forename: Mohammed Q
authors.initials: MQ
authors.lastname: Khan
authors.forename: Ahmed
authors.initials: A
authors.lastname: Helmy
authors.forename: Sahar
authors.initials: S
authors.lastname: Al-Thawadi
authors.forename: Mohammed N
authors.initials: MN
authors.lastname: Al-Ahdal
authors.forename: Nisreen
authors.initials: N
authors.lastname: Khalaf
authors.forename: Ahmed
authors.initials: A
authors.lastname: Al-Qahtani
authors.forename: Faisal M
authors.initials: FM
authors.lastname: Sanai
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D054357:Chemokine CXCL10 / Q000097:blood*; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics* / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011379:Prognosis; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a