title: Alanine aminotransferase, HCV RNA levels and pro-inflammatory and pro-fibrogenic cytokines/chemokines during acute hepatitis C virus infection.
abstract: BACKGROUND
  This study assessed the association of alanine-aminotransferase (ALT) and hepatitis C virus (HCV) RNA levels with pro-inflammatory and pro-fibrogenic cytokines and chemokines during acute HCV infection to provide further insight into the potential HCV immunopathogenesis.
  
  
  METHODS
  Participants in the ATAHC study, a prospective study of recent HCV infection, with detectable HCV RNA at the time of HCV detection were included. Plasma levels of 27 cytokines and chemokines were measured and their correlation with ALT and HCV RNA levels were assessed. Log10 transformed cytokines and ALT values were used in the analysis.
  
  
  RESULTS
  Among 117 individuals, the plasma levels of interferon-gamma inducible protein-10 (IP-10) and macrophage inflammatory protein-1beta (MIP-1β) were positively correlated with ALT levels (IP-10: r = 0.42, P < 0.001; MIP-1β: r = 0.29, P = 0.001) and HCV RNA levels (IP-10: rs = 0.44, P < 0.001; MIP-1β: rs = 0.43, P < 0.001). Using linear regression, after adjusting for sex, age, infection duration, symptomatic infection, HIV co-infection, interferon-lambda rs12979860 genotype, HCV genotype, and assay run, higher ALT levels (β = 0.20; 95 % CI: 0.07, 0.32; P = 0.002) and HCV RNA levels >400,000 IU/mL (vs. <8,500 IU/mL; β = 0.16; 95 % CI: 0.03, 0.28; P = 0.014) were independently associated with higher IP-10 levels. HCV RNA levels >400,000 IU/mL (vs. <8,500 IU/mL; β = 0.16; 95 % CI: 0.01, 0.31; P = 0.036) were associated with higher MIP-1β levels.
  
  
  CONCLUSIONS
  During acute HCV infection, high ALT and HCV RNA levels were associated with increased IP-10 levels, while high HCV RNA levels were also associated with increased MIP-1β levels. These data suggest that IP-10 and MIP-1β may have a role in HCV immuno-pathogenesis starting early in acute HCV infection.
authors.affiliation: The Kirby Institute, UNSW Australia, Wallace Wurth Building, Sydney, 2052, Australia. bhajarizadeh@kirby.unsw.edu.au.
authors.forename: Behzad
authors.initials: B
authors.lastname: Hajarizadeh
authors.affiliation: The Kirby Institute, UNSW Australia, Wallace Wurth Building, Sydney, 2052, Australia. flamoury@kirby.unsw.edu.au.
authors.forename: François Mj
authors.initials: FM
authors.lastname: Lamoury
authors.affiliation: Toronto Centre for Liver Disease, McLaughlin-Rotman Centre for Global Health, University of Toronto, Toronto, Canada. Jordan.Feld@uhn.ca.
authors.forename: Jordan J
authors.initials: JJ
authors.lastname: Feld
authors.affiliation: The Kirby Institute, UNSW Australia, Wallace Wurth Building, Sydney, 2052, Australia. jamin@kirby.unsw.edu.au.
authors.forename: Janaki
authors.initials: J
authors.lastname: Amin
authors.affiliation: Inflammation and Infection Research Centre, School of Medical Sciences, UNSW Australia, Sydney, Australia. e.keoshkerian@unsw.edu.au.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Keoshkerian
authors.affiliation: The Kirby Institute, UNSW Australia, Wallace Wurth Building, Sydney, 2052, Australia. gmatthews@kirby.unsw.edu.au.|HIV/Immunology/Infectious Diseases Clinical Services Unit, St Vincent's Hospital, Sydney, Australia. gmatthews@kirby.unsw.edu.au.
authors.forename: Gail V
authors.initials: GV
authors.lastname: Matthews
authors.affiliation: Burnet Institute, Melbourne, Australia. hellard@burnet.edu.au.
authors.forename: Margaret
authors.initials: M
authors.lastname: Hellard
authors.affiliation: The Kirby Institute, UNSW Australia, Wallace Wurth Building, Sydney, 2052, Australia. gdore@kirby.unsw.edu.au.|HIV/Immunology/Infectious Diseases Clinical Services Unit, St Vincent's Hospital, Sydney, Australia. gdore@kirby.unsw.edu.au.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Dore
authors.affiliation: Inflammation and Infection Research Centre, School of Medical Sciences, UNSW Australia, Sydney, Australia. a.lloyd@unsw.edu.au.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Lloyd
authors.affiliation: The Kirby Institute, UNSW Australia, Wallace Wurth Building, Sydney, 2052, Australia. jgrebely@kirby.unsw.edu.au.
authors.forename: Jason
authors.initials: J
authors.lastname: Grebely
authors.affiliation: The Kirby Institute, UNSW Australia, Wallace Wurth Building, Sydney, 2052, Australia. tapplegate@kirby.unsw.edu.au.
authors.forename: Tanya L
authors.initials: TL
authors.lastname: Applegate
mesh_terms: D000208:Acute Disease; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood*; D015415:Biomarkers; D018925:Chemokines / Q000097:blood; D060085:Coinfection; D016207:Cytokines / Q000097:blood*; D005260:Female; D005838:Genotype; D015658:HIV Infections; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000097:blood* / Q000175:diagnosis / Q000821:virology*; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D008297:Male; D011446:Prospective Studies; D019562:Viral Load
chemical_list: D015415:Biomarkers; D018925:Chemokines; D016207:Cytokines; D018836:Inflammation Mediators; D000410:Alanine Transaminase