Journal of Hepatology
Volume 39, Issue 2 , Pages 245-252 , August 2003

Effects of the CCR5-Δ32 mutation on antiviral treatment in chronic hepatitis C

  • Golo Ahlenstiel

      Affiliations

    • Medizinische Klinik u. Poliklinik I, -Allgemeine Innere Medizin-, Universität Bonn, Sigmund-Freud-Straße 25, D-53105 Bonn, Germany
    • ,
  • Thomas Berg

      Affiliations

    • Department of Internal Medicine, Center of Hepatology and Gastroenterology, Charité Campus, Virchow Klinikum, Berlin, Germany
    • ,
  • Rainer P Woitas

      Affiliations

    • Medizinische Klinik u. Poliklinik I, -Allgemeine Innere Medizin-, Universität Bonn, Sigmund-Freud-Straße 25, D-53105 Bonn, Germany
    • ,
  • Frank Grünhage

      Affiliations

    • Medizinische Klinik u. Poliklinik I, -Allgemeine Innere Medizin-, Universität Bonn, Sigmund-Freud-Straße 25, D-53105 Bonn, Germany
    • ,
  • Agathe Iwan

      Affiliations

    • Medizinische Klinik u. Poliklinik I, -Allgemeine Innere Medizin-, Universität Bonn, Sigmund-Freud-Straße 25, D-53105 Bonn, Germany
    • ,
  • Lothar Heß

      Affiliations

    • Institute of Experimental Hematology, University of Bonn, Bonn, Germany
    • ,
  • Hans H Brackmann

      Affiliations

    • Institute of Experimental Hematology, University of Bonn, Bonn, Germany
    • ,
  • Bernd Kupfer

      Affiliations

    • Institute of Medical Microbiology and Immunology, , University of Bonn, Bonn, Germany
    • ,
  • Andrea Schernick

      Affiliations

    • Department of Internal Medicine, Center of Hepatology and Gastroenterology, Charité Campus, Virchow Klinikum, Berlin, Germany
    • ,
  • Tilman Sauerbruch

      Affiliations

    • Medizinische Klinik u. Poliklinik I, -Allgemeine Innere Medizin-, Universität Bonn, Sigmund-Freud-Straße 25, D-53105 Bonn, Germany
    • ,
  • Ulrich Spengler

      Affiliations

    • Medizinische Klinik u. Poliklinik I, -Allgemeine Innere Medizin-, Universität Bonn, Sigmund-Freud-Straße 25, D-53105 Bonn, Germany
    • Corresponding Author InformationCorresponding author. Tel.: +49-228-287-6789; fax: +49-228-287-9822

Received 26 September 2002 ,Revised 11 April 2003 ,Accepted 11 April 2003.

References 

  1. Hepatitis C global prevalence. Wkly Epidemiol Rec 1997;72:341–4.
  2. Seeff LB, Buskell-Bales Z, Wright EC, Durako SJ, Alter HJ, Iber FL, et al.  Long-term mortality after transfusion-associated non-A, non-B hepatitis. The National Heart, Lung, and Blood Institute Study Group. N Engl J Med. 1992;327:1906–1911
  3. Tong MJ, el-Farra NS, Reikes AR, Co RL. Clinical outcomes after transfusion-associated hepatitis C. N Engl J Med. 1995;332:1463–1466
  4. Hoofnagle JH, di Bisceglie AM. The treatment of chronic viral hepatitis. N Engl J Med. 1997;336:347–356
  5. Tine F, Magrin S, Craxi A, Pagliaro L. Interferon for non-A, non-B chronic hepatitis. A meta-analysis of randomised clinical trials. J Hepatol. 1991;13:192–199
  6. Poynard T, Bedossa P, Chevallier M, Mathurin P, Lemonnier C, Trepo C, et al.  A comparison of three interferon alfa-2b regimens for the long-term treatment of chronic non-A, non-B hepatitis. Multicenter Study Group. N Engl J Med. 1995;332:1457–1462
  7. Carithers RL, Emerson SS. Therapy of hepatitis C: meta-analysis of interferon alfa-2b trials. Hepatology. 1997;26:83S–88S
  8. McHutchison JG, Gordon SC, Schiff ER, Shiffman ML, Lee WM, Rustgi VK, et al.  Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group. N Engl J Med. 1998;339:1485–1492
  9. Poynard T, Marcellin P, Lee SS, Niederau C, Minuk GS, Ideo G, et al.  Randomised trial of interferon alpha2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alpha2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. International Hepatitis Interventional Therapy Group (IHIT). Lancet. 1998;352:1426–1432
  10. Cacciarelli TV, Martinez OM, Gish RG, Villanueva JC, Krams SM. Immunoregulatory cytokines in chronic hepatitis C virus infection: pre- and posttreatment with interferon alfa. Hepatology. 1996;24:6–9
  11. Lau JY, Tam RC, Liang TJ, Hong Z. Mechanism of action of ribavirin in the combination treatment of chronic HCV infection. Hepatology. 2002;35:1002–1009
  12. Ning Q, Brown D, Parodo J, Cattral M, Gorczynski R, Cole E, et al.  Ribavirin inhibits viral-induced macrophage production of TNF, IL-1, the procoagulant fgl2 prothrombinase and preserves Th1 cytokine production but inhibits Th2 cytokine response. J Immunol. 1998;160:3487–3493
  13. Tam RC, Pai B, Bard J, Lim C, Averett DR, Phan UT, et al.  Ribavirin polarizes human T cell responses towards a Type 1 cytokine profile. J Hepatol. 1999;30:376–382
  14. Cramp ME, Rossol S, Chokshi S, Carucci P, Williams R, Naoumov NV. Hepatitis C virus-specific T-cell reactivity during interferon and ribavirin treatment in chronic hepatitis C. Gastroenterology. 2000;118:346–355
  15. Loetscher P, Uguccioni M, Bordoli L, Baggiolini M, Moser B, Chizzolini C, et al.  CCR5 is characteristic of Th1 lymphocytes. Nature. 1998;391:344–345
  16. Qin S, Rottman JB, Myers P, Kassam N, Weinblatt M, Loetscher M, et al.  The chemokine receptors CXCR3 and CCR5 mark subsets of T cells associated with certain inflammatory reactions. J Clin Invest. 1998;101:746–754
  17. Raport CJ, Gosling J, Schweickart VL, Gray PW, Charo IF. Molecular cloning and functional characterization of a novel human CC chemokine receptor (CCR5) for RANTES, MIP-1beta, and MIP-1alpha. J Biol Chem. 1996;271:17161–17166
  18. Dean M, Carrington M, Winkler C, Huttley GA, Smith MW, Allikmets R, et al.  Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study. Science. 1996;273:1856–1862
  19. Huang Y, Paxton WA, Wolinsky SM, Neumann AU, Zhang L, He T, et al.  The role of a mutant CCR5 allele in HIV-1 transmission and disease progression. Nat Med. 1996;2:1240–1243
  20. Liu R, Paxton WA, Choe S, Ceradini D, Martin SR, Horuk R, et al.  Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell. 1996;86:367–377
  21. Samson M, Libert F, Doranz BJ, Rucker J, Liesnard C, Farber CM, et al.  Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature. 1996;382:722–725
  22. Wu L, Paxton WA, Kassam N, Ruffing N, Rottman JB, Sullivan N, et al.  CCR5 levels and expression pattern correlate with infectability by macrophage-tropic HIV-1, in vitro. J Exp Med. 1997;185:1681–1691
  23. Garred P, Madsen HO, Petersen J, Marquart H, Hansen TM, Freiesleben Sorensen S, et al.  CC chemokine receptor 5 polymorphism in rheumatoid arthritis. J Rheumatol. 1998;25:1462–1465
  24. Gomez-Reino JJ, Pablos JL, Carreira PE, Santiago B, Serrano L, Vicario JL, et al.  Association of rheumatoid arthritis with a functional chemokine receptor, CCR5. Arthritis Rheum. 1999;42:989–992
  25. Zapico I, Coto E, Rodriguez A, Alvarez C, Torre JC, Alvarez V. CCR5 (chemokine receptor-5) DNA-polymorphism influences the severity of rheumatoid arthritis. Genes Immun. 2000;1:288–289
  26. Barcellos LF, Schito AM, Rimmler JB, Vittinghoff E, Shih A, Lincoln R, et al.  CC-chemokine receptor 5 polymorphism and age of onset in familial multiple sclerosis. Multiple Sclerosis Genetics Group. Immunogenetics. 2000;51:281–288
  27. Sellebjerg F, Madsen HO, Jensen CV, Jensen J, Garred P. CCR5 delta32, matrix metalloproteinase-9 and disease activity in multiple sclerosis. J Neuroimmunol. 2000;102:98–106
  28. Fischereder M, Luckow B, Hocher B, Wuthrich RP, Rothenpieler U, Schneeberger H, et al.  CC chemokine receptor 5 and renal-transplant survival. Lancet. 2001;357:1758–1761
  29. Hall IP, Wheatley A, Christie G, McDougall C, Hubbard R, Helms PJ. Association of CCR5 delta32 with reduced risk of asthma. Lancet. 1999;354:1264–1265
  30. Mitchell TJ, Walley AJ, Pease JE, Venables PJ, Wiltshire S, Williams TJ, et al.  Delta 32 deletion of CCR5 gene and association with asthma or atopy. Lancet. 2000;356:1491–1492
  31. Woitas RP, Ahlenstiel G, Iwan A, Rockstroh JK, Brackmann HH, Kupfer B, et al.  Frequency of the HIV-protective CC chemokine receptor 5-Delta32/Delta32 genotype is increased in hepatitis C. Gastroenterology. 2002;122:1721–1728
  32. Imberti L, Cariani E, Bettinardi A, Zonaro A, Albertini A, Primi D. An immunoassay for specific amplified HCV sequences. J Virol Methods. 1991;34:233–243
  33. Woitas RP, Lechmann M, Jung G, Kaiser R, Sauerbruch T, Spengler U. CD30 induction and cytokine profiles in hepatitis C virus core-specific peripheral blood T lymphocytes. J Immunol. 1997;159:1012–1018
  34. Intraobserver and interobserver variations in liver biopsy interpretation in patients with chronic hepatitis C. The French METAVIR Cooperative Study Group. Hepatology 1994;20:15–20.
  35. Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group. Hepatology. 1996;24:289–293
  36. Zylberberg H, Chaix ML, Brechot C. Infection with hepatitis C virus genotype 4 is associated with a poor response to interferon-alpha. Ann Intern Med. 2000;132:845–846
  37. Sherman M, Marinos G, Sedarati F. Infection with hepatitis C virus genotype 4 is associated with a poor response to interferon-alpha. Ann Intern Med. 2001;135:927–928
  38. Little RJA, Rubin DB. Statistical analysis with missing data. New York, NY: Wiley; 1989;
  39. Neumann AU, Lam NP, Dahari H, Gretch DR, Wiley TE, Layden TJ, et al.  Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy. Science. 1998;282:103–107
  40. Tsai SL, Liaw YF, Chen MH, Huang CY, Kuo GC. Detection of type 2-like T-helper cells in hepatitis C virus infection: implications for hepatitis C virus chronicity. Hepatology. 1997;25:449–458
  41. Andres PG, Beck PL, Mizoguchi E, Mizoguchi A, Bhan AK, Dawson T, et al.  Mice with a selective deletion of the CC chemokine receptors 5 or 2 are protected from dextran sodium sulfate-mediated colitis: lack of CC chemokine receptor 5 expression results in a NK1.1+ lymphocyte-associated Th2-type immune response in the intestine. J Immunol. 2000;164:6303–6312
  42. Tan SL, Katze MG. How hepatitis C virus counteracts the interferon response: the jury is still out on NS5A. Virology. 2001;284:1–12
  43. Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology. 2001;34:1225–1241
  44. Savoie L, Johnston JB. Hairy cell leukemia. Curr Treat Options Oncol. 2001;2:217–224
  45. Kloke O, Opalka B, Niederle N. Interferon alfa as primary treatment of chronic myeloid leukemia: long- term follow-up of 71 patients observed in a single center. Leukemia. 2000;14:389–392

PII: S0168-8278(03)00193-4

doi: 10.1016/S0168-8278(03)00193-4

Journal of Hepatology
Volume 39, Issue 2 , Pages 245-252 , August 2003

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