Journal of Hepatology
Volume 49, Issue 4 , Pages 548-556 , October 2008

DNA polymorphisms and response to treatment in patients with chronic hepatitis C: Results from the HALT-C trial

  • Timothy R. Morgan

      Affiliations

    • Division of Gastroenterology, University of California-Irvine, Irvine, CA, USA
    • Gastroenterology Service, VA Long Beach Healthcare System, Long Beach, CA, USA
    • Corresponding Author InformationCorresponding author. Tel.: +1 562 826 5756; fax: +1 562 826 5436.
  • ,
  • Richard W. Lambrecht

      Affiliations

    • Department of Medicine and The Liver-Biliary-Pancreatic Center, University of Connecticut Health Center, Farmington, CT, USA
  • ,
  • Herbert L. Bonkovsky

      Affiliations

    • Department of Medicine and The Liver-Biliary-Pancreatic Center, University of Connecticut Health Center, Farmington, CT, USA
    • Department of Molecular and Structural Biology and The Liver-Biliary-Pancreatic Center, University of Connecticut Health Center, Farmington, CT, USA
    • Carolinas Medical Center, Charlotte, NC, USA
  • ,
  • Raymond T. Chung

      Affiliations

    • Gastrointestinal Unit, Medical Services, Massachusetts General Hospital, and the Department of Medicine, Harvard Medical School, Boston, MA, USA
  • ,
  • Deepa Naishadham

      Affiliations

    • New England Research Institutes, Watertown, MA, USA
  • ,
  • Richard K. Sterling

      Affiliations

    • Hepatology Section, Virginia Commonwealth University Medical Center, Richmond, VA, USA
  • ,
  • Robert J. Fontana

      Affiliations

    • Division of Gastroenterology, University of Michigan, Ann Arbor, MI, USA
  • ,
  • William M. Lee

      Affiliations

    • Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA
  • ,
  • Marc G. Ghany

      Affiliations

    • Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA
  • ,
  • Elizabeth C. Wright

      Affiliations

    • Office of the Director, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA
  • ,
  • Thomas R. O’Brien

      Affiliations

    • Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA
  • ,
  • the HALT-C Trial Group

Received 20 December 2007 ,Revised 4 May 2008 ,Accepted 8 May 2008.

References 

  1. Bendicho MT, Guedes JC, Silva NN, Santana GO, dos Santos RR, Lyra AC, et al. Polymorphism of cytokine genes (TGF-beta1, IFN-gamma, IL-6, IL-10, and TNF-alpha) in patients with chronic pancreatitis. Pancreas. 2005;30:333–336
  2. Migita K, Miyazoe S, Maeda Y, Daikoku M, Abiru S, Ueki T, et al. Cytokine gene polymorphisms in Japanese patients with hepatitis B virus infection – association between TGF-beta1 polymorphisms and hepatocellular carcinoma. J Hepatol. 2005;42:505–510
  3. Yamada Y, Izawa H, Ichihara S, Takatsu F, Ishihara H, Hirayama H, et al. Prediction of the risk of myocardial infarction from polymorphisms in candidate genes. N Engl J Med. 2002;347:1916–1923
  4. Jover R, Zapater P, Castells A, Llor X, Andreu M, Cubiella J, et al. Mismatch repair status in the prediction of benefit from adjuvant fluorouracil chemotherapy in colorectal cancer. Gut. 2006;55:848–855
  5. Ruano G, Makowski G, Windemuth A, Kocherla M, Weiss D, Goethe JW, et al. High carrier prevalence of deficient and null alleles of CYP2 genes in a major USA hospital: implications for personalized drug safety. Personalized Med. 2006;3:131–137
  6. Ruano G, Thompson PD, Windemuth A, Smith A, Kocherla M, Holford TR, et al. Physiogenomic analysis links serum creatine kinase activities during statin therapy to vascular smooth muscle homeostasis. Pharmacogenomics. 2005;6:865–872
  7. Airoldi A, Zavaglia C, Silini E, Tinelli C, Martinetti M, Asti M, et al. Lack of a strong association between HLA class II, tumour necrosis factor and transporter associated with antigen processing gene polymorphisms and virological response to alpha-interferon treatment in patients with chronic hepatitis C. Eur J Immunogenet. 2004;31:259–265
  8. Constantini PK, Wawrzynowicz-Syczewska M, Clare M, Boron-Kaczmarska A, McFarlane IG, Cramp ME, et al. Interleukin-1, interleukin-10 and tumour necrosis factor-alpha gene polymorphisms in hepatitis C virus infection: an investigation of the relationships with spontaneous viral clearance and response to alpha-interferon therapy. Liver. 2002;22:404–412
  9. Dai CY, Chuang WL, Chang WY, Chen SC, Lee LP, Hsieh MY, et al. Tumor necrosis factor-alpha promoter polymorphism at position −308 predicts response to combination therapy in hepatitis C virus infection. J Infect Dis. 2006;193:98–101
  10. Edwards-Smith CJ, Jonsson JR, Purdie DM, Bansal A, Shorthouse C, Powell EE. Interleukin-10 promoter polymorphism predicts initial response of chronic hepatitis C to interferon alfa. Hepatology. 1999;30:526–530
  11. Knapp S, Hennig BJ, Frodsham AJ, Zhang L, Hellier S, Wright M, et al. Interleukin-10 promoter polymorphisms and the outcome of hepatitis C virus infection. Immunogenetics. 2003;55:362–369
  12. Mangia A, Santoro R, Piattelli M, Pazienza V, Grifa G, Iacobellis A, et al. IL-10 haplotypes as possible predictors of spontaneous clearance of HCV infection. Cytokine. 2004;25:103–109
  13. Schiemann U, Glas J, Torok P, Simperl C, Martin K, Konig A, et al. Response to combination therapy with interferon alfa-2a and ribavirin in chronic hepatitis C according to a TNF-alpha promoter polymorphism. Digestion. 2003;68:1–4
  14. Vidigal PG, Germer JJ, Zein NN. Polymorphisms in the interleukin-10, tumor necrosis factor-alpha, and transforming growth factor-beta1 genes in chronic hepatitis C patients treated with interferon and ribavirin. J Hepatol. 2002;36:271–277
  15. Yee LJ, Tang J, Gibson AW, Kimberly R, Van Leeuwen DJ, Kaslow RA. Interleukin 10 polymorphisms as predictors of sustained response in antiviral therapy for chronic hepatitis C infection. Hepatology. 2001;33:708–712
  16. Yu ML, Dai CY, Chiu CC, Lee LP, Lin ZY, Chen SC, et al. Tumor necrosis factor alpha promoter polymorphisms at position −308 in Taiwanese chronic hepatitis C patients treated with interferon-alpha. Antiviral Res. 2003;59:35–40
  17. Gewaltig J, Mangasser-Stephan K, Gartung C, Biesterfeld S, Gressner AM. Association of polymorphisms of the transforming growth factor-beta1 gene with the rate of progression of HCV-induced liver fibrosis. Clin Chim Acta. 2002;316:83–94
  18. Powell EE, Edwards-Smith CJ, Hay JL, Clouston AD, Crawford DH, Shorthouse C, et al. Host genetic factors influence disease progression in chronic hepatitis C. Hepatology. 2000;31:828–833
  19. Sonzogni L, Silvestri L, De Silvestri A, Gritti C, Foti L, Zavaglia C, et al. Polymorphisms of microsomal epoxide hydrolase gene and severity of HCV-related liver disease. Hepatology. 2002;36:195–201
  20. Tag CG, Mengsteab S, Hellerbrand C, Lammert F, Gressner AM, Weiskirchen R. Analysis of the transforming growth factor-beta1 (TGF-beta1) codon 25 gene polymorphism by LightCycler-analysis in patients with chronic hepatitis C infection. Cytokine. 2003;24:173–181
  21. Lee WM, Dienstag JL, Lindsay KL, Lok AS, Bonkovsky HL, Shiffman ML, et al. Evolution of the HALT-C Trial: pegylated interferon as maintenance therapy for chronic hepatitis C in previous interferon nonresponders. Control Clin Trials. 2004;25:472–492
  22. Shiffman ML, Di Bisceglie AM, Lindsay KL, Morishima C, Wright EC, Everson GT, et al. Peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C who have failed prior treatment. Gastroenterology. 2004;126:1015–1023
  23. Ishak K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F, et al. Histological grading and staging of chronic hepatitis. J Hepatol. 1995;22:696–699
  24. Bonkovsky HL, Naishadham D, Lambrecht RW, Chung RT, Hoefs JC, Nash SR, et al. Roles of iron and HFE mutations on severity and response to therapy during retreatment of advanced chronic hepatitis C. Gastroenterology. 2006;131:1440–1451
  25. Ferenci P. Predictors of response to therapy for chronic hepatitis C. Semin Liver Dis. 2004;24:25–31
  26. Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Goncales FL, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975–982
  27. Valenti L, Pulixi E, Fracanzani AL, Dongiovanni P, Maggioni M, Orsatti A, et al. TNFalpha genotype affects TNFalpha release, insulin sensitivity and the severity of liver disease in HCV chronic hepatitis. J Hepatol. 2005;43:944–950
  28. Gowans D, O’Sullivan A, Rollinson S, Roddam P, Groves M, Fegan C, et al. Allele and haplotype frequency at human leucocyte antigen class I/II and immunomodulatory cytokine loci in patients with myelodysplasia and acute myeloid leukaemia: in search of an autoimmune aetiology. Br J Haematol. 2002;117:541–545
  29. Klein W, Tromm A, Griga T, Fricke H, Folwaczny C, Hocke M, et al. The IL-10 gene is not involved in the predisposition to inflammatory bowel disease. Electrophoresis. 2000;21:3578–3582
  30. Trompet S, Pons D, De Craen AJ, Slagboom P, Shepherd J, Blauw GJ, et al. Genetic variation in the interleukin-10 gene promoter and risk of coronary and cerebrovascular events: the PROSPER study. Ann NY Acad Sci. 2007;1100:189–198
  31. Turner DM, Williams DM, Sankaran D, Lazarus M, Sinnott PJ, Hutchinson IV. An investigation of polymorphism in the interleukin-10 gene promoter. Eur J Immunogenet. 1997;24:1–8
  32. Nieters A, Brems S, Becker N. Cross-sectional study on cytokine polymorphisms, cytokine production after T-cell stimulation and clinical parameters in a random sample of a German population. Hum Genet. 2001;108:241–248
  33. Nelson DR, Tu Z, Soldevila-Pico C, Abdelmalek M, Zhu H, Xu YL, et al. Long-term interleukin 10 therapy in chronic hepatitis C patients has a proviral and anti-inflammatory effect. Hepatology. 2003;38:859–868
  34. Reuss E, Fimmers R, Kruger A, Becker C, Rittner C, Hohler T. Differential regulation of interleukin-10 production by genetic and environmental factors – a twin study. Genes Immun. 2002;3:407–413
  35. Bayley JP, Ottenhoff TH, Verweij CL. Is there a future for TNF promoter polymorphisms?. Genes Immun. 2004;5:315–329
  36. Bonkovsky HL, Salek J. No role of the −2518 promoter polymorphism of monocyte chemotactic protein-1 in chronic hepatitis C. Gastroenterology. 2005;129:1361–1362
  37. Hellier S, Frodsham AJ, Hennig BJ, Klenerman P, Knapp S, Ramaley P, et al. Association of genetic variants of the chemokine receptor CCR5 and its ligands, RANTES and MCP-2, with outcome of HCV infection. Hepatology. 2003;38:1468–1476
  38. Conjeevaram HS, Fried MW, Jeffers LJ, Terrault NA, Wiley-Lucas TE, Afdhal N, et al. Peginterferon and ribavirin treatment in African American and Caucasian American patients with hepatitis C genotype 1. Gastroenterology. 2006;131:470–477
  39. Hadziyannis SJ, Sette H, Morgan TR, Balan V, Diago M, Marcellin P, et al. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med. 2004;140:346–355
  40. Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358:958–965

 Financial relationships of the authors with Hoffmann-La Roche, Inc., are as follows: T.R. Morgan is a consultant, is on the speaker’s bureau and receives research support; R.T. Chung receives research support; R.K. Sterling is a consultant, on the speaker’s bureau, and receives research support; R.J. Fontana is on the speaker’s bureau; and W.M. Lee receives research support. Authors with no financial relationships related to this project are: R.W. Lambrecht, H.L. Bonkovsky, D. Naishadham, M.G. Ghany, E.C. Wright, and T.R. O’Brien. This is a NIH funded study.

☆☆ This is publication number 30 from the HALT-C Trial Group.

PII: S0168-8278(08)00354-1

doi: 10.1016/j.jhep.2008.05.011

Journal of Hepatology
Volume 49, Issue 4 , Pages 548-556 , October 2008