title: Plasma levels of growth-related oncogene (CXCL1-3) associated with fibrosis and platelet counts in HCV-infected patients.
abstract: BACKGROUND
  Fibrosis progression in hepatitis C virus (HCV)-infected patients varies greatly between individuals. Chemokines recruit immune cells to the infected liver and may thus play a role in the fibrosis process.
  
  
  OBJECTIVE
  To investigate plasma levels of a diverse chemokine panel in relation to liver fibrosis.
  
  
  METHODS
  African-American and Caucasian HCV genotype 1 infected patients were treated with peginterferon (pegIFN) and ribavirin (RBV) for 48 weeks (VIRAHEP-C cohort). Plasma levels of 13 cytokines were studied at baseline (n = 386). Subsequently, GROα levels were assessed in a sub cohort (n = 99) at baseline, and at 4 and 12 weeks after start of pegIFN/RBV treatment.
  
  
  RESULTS
  Increased severity of fibrosis (Ishak fibrosis score 0-2 vs. 3-6) was associated with increased plasma IP-10 (CXCL10) and IL-8 (CXCL8) levels, and decreased plasma levels of the chemokine growth-related oncogene (GRO, CXCL1-3). Plasma GRO levels were also positively correlated with platelet counts, and were higher in African-American as compared to Caucasian patients. In response to pegIFN/RBV treatment, GROα levels increased in Caucasian but not African-American patients from week 4 onwards.
  
  
  CONCLUSIONS
  The association with severity of fibrosis and platelet count positions plasma GRO as a potential biomarker for liver fibrosis in HCV-infected patients. The secretion of GRO by platelets may explain the correlation between GRO plasma level and platelet count. The ethnic difference in GRO levels both pre-treatment and in response to pegIFN/RBV might be driven by a genetic polymorphism in GROα associated with higher plasma levels and more common in the African-American population.
authors: Janssen Research and Development, Beerse, Belgium.
authors: S
authors: http://orcid.org/0000-0002-0073-6355
authors: S
authors: Johansson
authors: Janssen Research and Development, Beerse, Belgium.
authors: W
authors: W
authors: Talloen
authors: Janssen Research and Development, Beerse, Belgium.
authors: M
authors: M
authors: Tuefferd
authors: University of North Carolina, Chapel Hill, NC, USA.
authors: J M
authors: JM
authors: Darling
authors: Janssen Research and Development, Beerse, Belgium.
authors: A
authors: A
authors: Scholliers
authors: Janssen Research and Development, Beerse, Belgium.
authors: G
authors: G
authors: Fanning
authors: University of North Carolina, Chapel Hill, NC, USA.
authors: M W
authors: MW
authors: Fried
authors: Janssen Research and Development, Beerse, Belgium.
authors: J
authors: J
authors: Aerssens
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers; D054360:Chemokine CXCL1; D018925:Chemokines / Q000097:blood*; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000235:genetics; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D016209:Interleukin-8; D007378:Interleukins; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; C475829:CXCL1 protein, human; C508606:CXCL8 protein, human; D054360:Chemokine CXCL1; D018925:Chemokines; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D016209:Interleukin-8; D007378:Interleukins; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a