Journal of Hepatology
Volume 53, Issue 2 , Pages 252-260 , August 2010

CD4+ T-lymphocyte telomere length is related to fibrosis stage, clinical outcome and treatment response in chronic hepatitis C virus infection

  • Matthew Hoare

      Affiliations

    • Department of Medicine, School of Clinical Medicine, University of Cambridge, Cambridge, UK
    • ,
  • William T.H. Gelson

      Affiliations

    • Department of Medicine, School of Clinical Medicine, University of Cambridge, Cambridge, UK
    • ,
  • Abhi Das

      Affiliations

    • Department of Immunology, University College London, London, UK
    • ,
  • Jean M. Fletcher

      Affiliations

    • Department of Immunology, University College London, London, UK
    • ,
  • Susan E. Davies

      Affiliations

    • Department of Pathology, University of Cambridge, Cambridge, UK
    • ,
  • Martin D. Curran

      Affiliations

    • Clinical Microbiology and Public Health Laboratory, Health Protection Agency, Addenbrooke’s Hospital, Cambridge, UK
    • ,
  • Sarah L. Vowler

      Affiliations

    • Centre for Applied Medical Statistics, Department of Public Health and Primary Care, University of Cambridge, Institute of Public Health, Forvie Site, Robinson Way, Cambridge, UK
    • ,
  • Mala K. Maini

      Affiliations

    • Department of Immunology, University College London, London, UK
    • ,
  • Arne N. Akbar

      Affiliations

    • Department of Immunology, University College London, London, UK
    • ,
  • Graeme J.M. Alexander

      Affiliations

    • Department of Medicine, School of Clinical Medicine, University of Cambridge, Cambridge, UK
    • Corresponding Author InformationCorresponding author. Address: Department of Medicine, Box 157, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 2QQ, UK. Tel.: +44 1223 336008; fax: +44 1223 216111.

Received 9 November 2009 ,Revised 4 February 2010 ,Accepted 3 March 2010.

References 

  1. Levine RA, Sanderson SO, Ploutz-Snyder R, Murray F, Kay E, Hegarty J, et al. Assessment of fibrosis progression in untreated irish women with chronic hepatitis C contracted from immunoglobulin anti-D. Clin Gastroenterol Hepatol. 2006;4(10):1271–1277
  2. Ryder SD, Irving WL, Jones DA, Neal KR, Underwood JC. Progression of hepatic fibrosis in patients with hepatitis C: a prospective repeat liver biopsy study. Gut. 2004;53(3):451–455
  3. Missiha SB, Ostrowski M, Heathcote EJ. Disease progression in chronic hepatitis C: modifiable and nonmodifiable Factors. Gastroenterology. 2008;134:1699–1714
  4. Poynard T, Bedossa P, Opolon P. Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups. Lancet. 1997;349(9055):825–832
  5. Poynard T, Ratziu V, Charlotte F, Goodman Z, McHutchison J, Albrecht J. Rates and risk factors of liver fibrosis progression in patients with chronic hepatitis C. J Hepatol. 2001;34(5):730–739
  6. Pradat P, Voirin N, Tillmann HL, Chevallier M, Trepo C. Progression to cirrhosis in hepatitis C patients: an age-dependent process. Liver Int. 2007;27(3):335–339
  7. Linton PJ, Dorshkind K. Age-related changes in lymphocyte development and function. Nat Immunol. 2004;5(2):133–139
  8. Pawelec G, Akbar A, Caruso C, Solana R, Grubeck-Loebenstein B, Wikby A. Human immunosenescence: is it infectious?. Immunol Rev. 2005;205:257–268
  9. Cawthon RM, Smith KR, O’Brien E, Sivatchenko A, Kerber RA. Association between telomere length in blood and mortality in people aged 60 years or older. Lancet. 2003;361(9355):393–395
  10. Ferguson FG, Wikby A, Maxson P, Olsson J, Johansson B. Immune parameters in a longitudinal study of a very old population of Swedish people: a comparison between survivors and nonsurvivors. J Gerontol A Biol Sci Med Sci. 1995;50(6):B378–B382
  11. Akbar AN, Beverley PC, Salmon M. Will telomere erosion lead to a loss of T-cell memory?. Nat Rev Immunol. 2004;4(9):737–743
  12. d’Adda di FF, Reaper PM, Clay-Farrace L, Fiegler H, Carr P, Von ZT, et al. A DNA damage checkpoint response in telomere-initiated senescence. Nature. 2003;426(6963):194–198
  13. Hao LY, Strong MA, Greider CW. Phosphorylation of H2AX at short telomeres in T cells and fibroblasts. J Biol Chem. 2004;279(43):45148–45154
  14. Papazoglu C, Mills AA. P53: at the crossroad between cancer and ageing. J Pathol. 2007;211(2):124–133
  15. Soares MV, Plunkett FJ, Verbeke CS, Cook JE, Faint JM, Belaramani LL, et al. Integration of apoptosis and telomere erosion in virus-specific CD8+ T cells from blood and tonsils during primary infection. Blood. 2004;103(1):162–167
  16. Plunkett FJ, Soares MV, Annels N, Hislop A, Ivory K, Lowdell M, et al. The flow cytometric analysis of telomere length in antigen-specific CD8+ T cells during acute Epstein–Barr virus infection. Blood. 2001;97(3):700–707
  17. Fletcher JM, Vukmanovic-Stejic M, Dunne PJ, Birch KE, Cook JE, Jackson SE, et al. Cytomegalovirus-specific CD4+ T cells in healthy carriers are continuously driven to replicative exhaustion. J Immunol. 2005;175(12):8218–8225
  18. Vescovini R, Biasini C, Fagnoni FF, Telera AR, Zanlari L, Pedrazzoni M, et al. Massive load of functional effector CD4+ and CD8+ T cells against cytomegalovirus in very old subjects. J Immunol. 2007;179(6):4283–4291
  19. Manfras BJ, Weidenbach H, Beckh KH, Kern P, Moller P, Adler G, et al. Oligoclonal CD8+ T-cell expansion in patients with chronic hepatitis C is associated with liver pathology and poor response to interferon-alpha therapy. J Clin Immunol. 2004;24(3):258–271
  20. Kitay-Cohen Y, Goldberg-Bittman L, Hadary R, Fejgin MD, Amiel A. Telomere length in Hepatitis C. Cancer Genet Cytogenet. 2008;187(1):34–38
  21. Antonucci G, Longo MA, Angeletti C, Vairo F, Oliva A, Comandini UV, et al. The effect of age on response to therapy with peginterferon alpha plus ribavirin in a cohort of patients with chronic HCV hepatitis including subjects older than 65 yr. Am J Gastroenterol. 2007;102(7):1383–1391
  22. Elefsiniotis IS, Pavlidis C, Ketikoglou I, Koutsounas S, Scarmeas N, Pantazis KD, et al. Patient’s age modifies the impact of the proposed predictors of sustained virological response in chronic hepatitis C patients treated with PEG-interferon plus ribavirin. Eur J Intern Med. 2008;19(4):266–270
  23. Reed JR, Vukmanovic-Stejic M, Fletcher JM, Soares MV, Cook JE, Orteu CH, et al. Telomere erosion in memory T cells induced by telomerase inhibition at the site of antigenic challenge in vivo. J Exp Med. 2004;199(10):1433–1443
  24. Baerlocher GM, Mak J, Tien T, Lansdorp PM. Telomere length measurement by fluorescence in situ hybridization and flow cytometry: tips and pitfalls. Cytometry. 2002;47(2):89–99
  25. Aikata H, Takaishi H, Kawakami Y, Takahashi S, Kitamoto M, Nakanishi T, et al. Telomere reduction in human liver tissues with age and chronic inflammation. Exp Cell Res. 2000;256(2):578–582
  26. Wiemann SU, Satyanarayana A, Tsahuridu M, Tillmann HL, Zender L, Klempnauer J, et al. Hepatocyte telomere shortening and senescence are general markers of human liver cirrhosis. FASEB J. 2002;16(9):935–942
  27. Barnes E, Ward SM, Kasprowicz VO, Dusheiko G, Klenerman P, Lucas M. Ultra-sensitive class I tetramer analysis reveals previously undetectable populations of antiviral CD8+ T cells. Eur J Immunol. 2004;34(6):1570–1577
  28. Klenerman P, Hill A. T cells and viral persistence: lessons from diverse infections. Nat Immunol. 2005;6(9):873–879
  29. Hoofnagle JH, Seeff LB. Peginterferon and ribavirin for chronic hepatitis C. N Engl J Med. 2006;355(23):2444–2451

PII: S0168-8278(10)00268-0

doi: 10.1016/j.jhep.2010.03.005

Journal of Hepatology
Volume 53, Issue 2 , Pages 252-260 , August 2010

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