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Pharmacogenomic perspectives of chronic hepatitis C virus (HCV) infection

The Pharmacogenomics Journal volume 4, pages 171–174 (2004)Cite this article

Chronic hepatitis C virus (HCV) infection is found in about 3% of the world population and has become one of the major causes of liver cirrhosis and hepatocellular carcinoma. Treatment for HCV infection is widely available in places where it is affordable, and a variety of pharmacogenetic analyses have already suggested that differential response to HCV therapy can be related to coding and noncoding (promoter/regulatory) sequence variations in the human genome. However, most studies have been compromised by small sample size, nonrepresentative subject selection, and/or low-resolution genotyping. Systematic investigations of larger, representative populations will be essential for the generation of consensus data to guide experimental and clinical research.

Treatment of HCV infection is suboptimal: many patients do not respond to or tolerate the typical full-dose combination therapy (FCT = 48-week-long injection of interferon alpha 2b plus daily oral dose of ribavirin) or modified FCT (MFCT = peginterferon α2b plus ribavirin). In particular, fewer than half of patients with genotype 1 HCV infection can achieve sustained viral suppression (below level of detection by polymerase chain reaction) for at least 24 weeks after completing FCT or MFCT.1,2 Likewise, only a minority of treated patients exhibit other forms of therapeutic success characterized by normalization of alanine aminotransferase (ALT) concentration and improvement in histological grading of liver biopsy.

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References

  1. 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.

    Article  CAS  Google Scholar 

  2. Zeuzem S, Feinman SV, Rasenack J, Heathcote EJ, Lai MY, Gane E et al. Peginterferon alfa-2a in patients with chronic hepatitis C. N Engl J Med 2000; 343: 1666–1672.

    Article  CAS  Google Scholar 

  3. Shiratori Y, Kato N, Yokosuka O, Imazeki F, Hashimoto E, Hayashi N et al. Predictors of the efficacy of interferon therapy in chronic hepatitis C virus infection. Tokyo–Chiba Hepatitis Research Group. Gastroenterology 1997; 113: 558–566.

    Article  CAS  Google Scholar 

  4. Nakamuta M, Fukutomi T, Shimohashi N, Kinukawa N, Uchimura K, Tada S et al. Kinetics of the hepatitis C virus during interferon therapy as a marker of therapeutic response. J Gastroenterol Hepatol 2001; 16: 29–33.

    Article  CAS  Google Scholar 

  5. Bressler BL, Guindi M, Tomlinson G, Heathcote J . High body mass index is an independent risk factor for nonresponse to antiviral treatment in chronic hepatitis C. Hepatology 2003; 38: 639–644.

    Article  CAS  Google Scholar 

  6. 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.

    Article  CAS  Google Scholar 

  7. Knapp S, Yee LJ, Frodsham AJ, Hennig BJ, Hellier S, Zhang L et al. Polymorphisms in interferon-induced genes and the outcome of hepatitis C virus infection: roles of MxA, OAS-1 and PKR. Genes Immun 2003; 4: 411–419.

    Article  CAS  Google Scholar 

  8. Hijikata M, Ohta Y, Mishiro S . Identification of a single nucleotide polymorphism in the MxA gene promoter (G/T at nt −88) correlated with the response of hepatitis C patients to interferon. Intervirology 2000; 43: 124–127.

    Article  CAS  Google Scholar 

  9. Hijikata M, Mishiro S, Miyamoto C, Furuichi Y, Hashimoto M, Ohta Y . Genetic polymorphism of the MxA gene promoter and interferon responsiveness of hepatitis C patients: revisited by analyzing two SNP sites (−123 and −88) in vivo and in vitro. Intervirology 2001; 44: 379–382.

    Article  CAS  Google Scholar 

  10. Antonelli G, Simeoni E, Turriziani O, Tesoro R, Redaelli A, Roffi L et al. Correlation of interferon-induced expression of MxA mRNA in peripheral blood mononuclear cells with the response of patients with chronic active hepatitis C to IFN-alpha therapy. J Interferon Cytokine Res 1999; 19: 243–251.

    Article  CAS  Google Scholar 

  11. Thio CL, Thomas DL, Carrington M . Chronic viral hepatitis and the human genome. Hepatology 2000; 31: 819–827.

    Article  CAS  Google Scholar 

  12. Alric L, Izopet J, Fort M, Vinel JP, Fontenelle P, Orfila C et al. Study of the association between major histocompatibility complex class II genes and the response to interferon alpha in patients with chronic hepatitis C infection. Hum Immunol 1999; 60: 516–523.

    Article  CAS  Google Scholar 

  13. Sugimoto Y, Kuzushita N, Takehara T, Kanto T, Tatsumi T, Miyagi T et al. A single nucleotide polymorphism of the low molecular mass polypeptide 7 gene influences the interferon response in patients with chronic hepatitis C. J Viral Hepat 2002; 9: 377–384.

    Article  CAS  Google Scholar 

  14. Dorak MT, Folayan GO, Niwas S, Yee LJ, Tang J, van Leevan DJ et al. C-C chemokine receptor 2 (CCR2) and CCR5 genotypes in patients treated for hepatitis C virus infection. Immunol Res 2002; 26: 167–175.

    Article  CAS  Google Scholar 

  15. Yee LJ, Perez KA, Tang J, van Leeuwen DJ, Kaslow RA . Association of CTLA4 polymorphisms with sustained response to interferon and ribavirin therapy for chronic hepatitis C virus infection. J Infect Dis 2003; 187: 1264–1271.

    Article  CAS  Google Scholar 

  16. Dupuis S, Jouanguy E, Al-Hajjar S, Fieschi C, Al-Mohsen IZ, Al-Jumaah S et al. Impaired response to interferon-alpha/beta and lethal viral disease in human STAT1 deficiency. Nat Genet 2003; 33: 388–391.

    Article  CAS  Google Scholar 

  17. Mogensen KE, Lewerenz M, Reboul J, Lutfalla G, Uze G . The type I interferon receptor: structure, function, and evolution of a family business. J Interferon Cytokine Res 1999; 19: 1069–1098.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, University of Alabama at Birmingham, Birmingham, 35294, AL, USA

    J Tang & R A Kaslow

  2. Department of Epidemiology, University of Alabama at Birmingham, Birmingham, 35294, AL, USA

    R A Kaslow

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  1. J Tang
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  2. R A Kaslow
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Correspondence to J Tang.

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Tang, J., Kaslow, R. Pharmacogenomic perspectives of chronic hepatitis C virus (HCV) infection. Pharmacogenomics J 4, 171–174 (2004). https://doi.org/10.1038/sj.tpj.6500246

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