title: Systemic and intrahepatic interferon-gamma-inducible protein 10 kDa predicts the first-phase decline in hepatitis C virus RNA and overall viral response to therapy in chronic hepatitis C.
abstract: High systemic levels of interferon-gamma-inducible protein 10 kDa (IP-10) at onset of combination therapy for chronic hepatitis C virus (HCV) infection predict poor outcome, but details regarding the impact of IP-10 on the reduction of HCV RNA during therapy remain unclear. In the present study, we correlated pretreatment levels of IP-10 in liver biopsies (n = 73) and plasma (n = 265) with HCV RNA throughout therapy within a phase III treatment trial (DITTO-HCV). Low levels of plasma or intrahepatic IP-10 were strongly associated with a pronounced reduction of HCV RNA during the first 24 hours of treatment in all patients (P < 0.0001 and P = 0.002, respectively) as well as when patients were grouped as genotype 1 or 4 (P = 0.0008 and P = 0.01) and 2 or 3 (P = 0.002, and P = 0.02). Low plasma levels of IP-10 also were predictive of the absolute reduction of HCV RNA (P < 0.0001) and the maximum reduction of HCV RNA in the first 4 days of treatment (P < 0.0001) as well as sustained virological response (genotype 1/4; P < 0.0001). To corroborate the relationship between early viral decline and IP-10, pretreatment plasma samples from an independent phase IV trial for HCV genotypes 2/3 (NORDynamIC trial; n = 382) were analyzed. The results confirmed an association between IP-10 and the immediate reduction of HCV RNA in response to therapy (P = 0.006). In contrast, pretreatment levels of IP-10 in liver or in plasma did not affect the decline of HCV RNA between days 8 and 29, i.e., the second-phase decline, or later time points in any of these cohorts.
  
  
  CONCLUSIONS
  In patients with chronic hepatitis C, low levels of intrahepatic and systemic IP-10 predict a favorable first-phase decline of HCV RNA during therapy with pegylated interferon and ribavirin for genotypes of HCV.
authors.affiliation: Department of Infectious Diseases, University of Gothenburg, Sweden.
authors.forename: Galia
authors.initials: G
authors.lastname: Askarieh
authors.forename: Asa
authors.initials: A
authors.lastname: Alsiö
authors.forename: Paolo
authors.initials: P
authors.lastname: Pugnale
authors.forename: Francesco
authors.initials: F
authors.lastname: Negro
authors.forename: Carlo
authors.initials: C
authors.lastname: Ferrari
authors.forename: Avidan U
authors.initials: AU
authors.lastname: Neumann
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Pawlotsky
authors.forename: Solko W
authors.initials: SW
authors.lastname: Schalm
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.forename: Gunnar
authors.initials: G
authors.lastname: Norkrans
authors.forename: Johan
authors.initials: J
authors.lastname: Westin
authors.forename: Jonas
authors.initials: J
authors.lastname: Söderholm
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Hellstrand
authors.forename: Martin
authors.initials: M
authors.lastname: Lagging
mesh_terms: D000328:Adult; D054357:Chemokine CXCL10 / Q000097:blood / Q000378:metabolism*; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use; D011379:Prognosis; D012367:RNA, Viral / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a