title: CD4+ T-lymphocyte telomere length is related to fibrosis stage, clinical outcome and treatment response in chronic hepatitis C virus infection.
abstract: OBJECTIVE
  Increasing age is associated with impaired immune function and in chronic HCV infection specifically, with progressive fibrosis, liver failure, HCC and impaired responses to antiviral therapy. T-lymphocyte telomere length declines with age. We hypothesised that shorter T-lymphocyte telomere length would be associated with poor clinical outcome in HCV infection.
  
  
  METHODS
  Circulating T-lymphocyte telomere length, an objective measure of immune senescence, was measured by flow-FISH in 135 HCV-RNA-positive, treatment-naïve patients and 41 healthy controls in relation to clinical outcome.
  
  
  RESULTS
  Shorter CD4+CD45RO+ T-lymphocyte telomeres were associated with severe fibrosis (p=0.003), independent of male sex (p=0.04), CMV positivity (p=0.003), previous HBV infection (p=0.007), and age (p=ns) in viraemic patients compared to controls. There were inverse correlations between CD4+CD45RO+ telomere length and fibrosis stage (p<0.001), portal tract inflammatory grade (p=0.035), prothrombin time (p<0.001) and bilirubin (p=0.001). One hundred and twenty-four viraemic individuals were followed prospectively to a composite endpoint of death, hepatic decompensation or HCC. Independent of age, those with shorter CD4+CD45RO+ telomeres were less likely to be complication free after 2-years than those with longer telomeres (86% versus 96%, p=0.009) with an age-adjusted hazard ratio of 0.93 (0.90-0.96). In addition, CD4+CD45RO+ telomere length predicted successful antiviral therapy (p=0.001) independent of other factors.
  
  
  CONCLUSIONS
  CD4+ T-lymphocyte telomere length, independent of age, was related to inflammatory grade, fibrosis stage, laboratory indices of severity, subsequent hepatic decompensation and treatment outcome in patients with chronic HCV infection.
authors.affiliation: Department of Medicine, School of Clinical Medicine, University of Cambridge, Cambridge, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Hoare
authors.forename: William T H
authors.initials: WT
authors.lastname: Gelson
authors.forename: Abhi
authors.initials: A
authors.lastname: Das
authors.forename: Jean M
authors.initials: JM
authors.lastname: Fletcher
authors.forename: Susan E
authors.initials: SE
authors.lastname: Davies
authors.forename: Martin D
authors.initials: MD
authors.lastname: Curran
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Vowler
authors.forename: Mala K
authors.initials: MK
authors.lastname: Maini
authors.forename: Arne N
authors.initials: AN
authors.lastname: Akbar
authors.forename: Graeme J M
authors.initials: GJ
authors.lastname: Alexander
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D001706:Biopsy; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D016174:Hepacivirus; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011379:Prognosis; D012044:Regression Analysis; D012720:Severity of Illness Index; D016615:Telomere / Q000473:pathology*; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents
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