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Randomized trial of peginterferon α-2a plus ribavirin versus peginterferon α-2b plus ribavirin for chronic hepatitis C in Japanese patients

  • Original Article—Liver, Pancreas, and Biliary Tract
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Abstract

Background

Pegylated interferon (PegIFN) plus ribavirin is the standard therapy for patients with chronic hepatitis C genotype 1. Although several randomized clinical trials have compared PegIFNα-2a with PegIFNα-2b, these 2 regimens have not been directly compared in Asian patients. We, therefore, compared the safety and antiviral efficacy of these agents in Japanese patients.

Methods

A total of 201 PegIFN-naïve, chronic hepatitis C patients were randomly assigned to once-weekly PegIFNα-2a (180 μg) or PegIFNα-2b (60–150 μg) plus ribavirin. We compared the sustained virological response (SVR) rates between the 2 regimens and analyzed their effects in relation to baseline characteristics, including single nucleotide polymorphisms (SNPs) near the interleukin-28B (IL28B) gene (rs8099917).

Results

PegIFNα-2a was associated with a higher SVR rate than PegIFNα-2b (65.3 vs. 51.0%, P = 0.039). PegIFNα-2a and SNPs near IL28B independently predicted SVR (odds ratio 2.36; 95% confidence interval [CI] 1.19–15.50, and odds ratio 7.31; 95% CI 3.45–4.68, respectively) in logistic regression analysis. PegIFNα-2a was more effective than PegIFNα-2b (81.8 vs. 62.7%, P = 0.014) in IL28B TT genotype patients, despite similarly low SVR rates in patients with TG or GG genotypes (36.4 vs. 35.9%). Patients weighing <60 kg, women, and patients aged >60 years had significantly higher SVR rates with PegIFNα-2a than with PegIFNα-2b (63.9, 61.3, and 67.3% vs. 43.8, 43.3,and 39.2%, respectively).

Conclusions

PegIFNα-2a plus ribavirin resulted in higher SVR rates than PegIFNα-2b plus ribavirin in Japanese patients. PegIFNα-2a-based treatment should therefore be the preferred choice for women, older or low-weight patients, and those with the IL28B TT genotype.

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References

  1. World Health Organization. Global surveillance and control of hepatitis C. J Viral Hepat. 1999;6:35–47.

    Article  Google Scholar 

  2. Izumi N, Nishiguchi S, Hino K, Suzuki F, Kumada H, Itoh Y, et al. Management of hepatitis C: report of the Consensus Meeting at the 45th Annual Meeting of the Japan Society of Hepatology. Hepatol Res. 2010;40:347–68.

    Article  Google Scholar 

  3. Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Gonçales FL Jr, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975–82.

    Article  PubMed  CAS  Google Scholar 

  4. Hoofnagle JH, Seeff LB. Peginterferon and ribavirin for chronic hepatitis C. N Engl J Med. 2006;355:2444–51.

    Article  PubMed  CAS  Google Scholar 

  5. Yoshida H, Tateishi R, Arakawa Y, Sata M, Fujiyama S, Nishiguchi S, et al. Benefit of interferon therapy in hepatocellular carcinoma prevention for individual patients with chronic hepatitis C. Gut. 2004;53:425–30.

    Article  PubMed  CAS  Google Scholar 

  6. McHutchison JG, Lawitz EJ, Shiffman ML, Muir AJ, Galler GW, McCone J, et al. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med. 2009;361:580–93.

    Article  PubMed  CAS  Google Scholar 

  7. Rumi MG, Aghemo A, Prati GM, D’Ambrosio R, Donato MF, Soffredini R, et al. Randomized study of peginterferon-α2a plus ribavirin vs peginterferon-α2b plus ribavirin in chronic hepatitis C. Gastroenterology. 2010;138:108–15.

    Article  PubMed  CAS  Google Scholar 

  8. Ascione A, De Luca M, Tartaglione MT, Lampasi F, Di Costanzo GG, Lanza AG, et al. Peginterferon alfa-2a plus ribavirin is more effective than peginterferon alfa-2b plus ribavirin for treating chronic hepatitis C virus infection. Gastroenterology. 2010;138:116–22.

    Article  PubMed  CAS  Google Scholar 

  9. Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group. Hepatology. 1996;24:289–93.

    Article  PubMed  CAS  Google Scholar 

  10. Szczepaniak LS, Nurenberg P, Leonard D, Browning JD, Reingold JS, Grundy S, et al. Magnetic resonance spectroscopy to measure hepatic triglyceride content: prevalence of hepatic steatosis in the general population. Am J Physiol Endocrinol Metab. 2005;288:462–8.

    Article  Google Scholar 

  11. Ito K, Higami K, Masaki N, Sugiyama M, Mukaide M, Saito H, et al. The rs8099917 polymorphism, when determined by a suitable genotyping method, is a better predictor for response to pegylated alpha interferon/ribavirin therapy in Japanese patients than other single nucleotide polymorphisms associated with interleukin-28B. J Clin Microbiol. 2011;49:1853–60.

    Article  PubMed  CAS  Google Scholar 

  12. Ohnishi Y, Tanaka T, Ozaki K, Yamada R, Suzuki H, Nakamura Y. A high-throughput SNP typing system for genome-wide association studies. J Hum Genet. 2001;46:471–7.

    Article  PubMed  CAS  Google Scholar 

  13. Awad T, Thorlund K, Hauser G, Stimac D, Mabrouk M, Gluud C. Peginterferon alpha-2a is associated with higher sustained virological response than peginterferon alfa-2b in chronic hepatitis C: systematic review of randomized trials. Hepatology. 2010;51:1176–84.

    Article  PubMed  CAS  Google Scholar 

  14. Oze T, Hiramatsu N, Yakushijin T, Kurokawa M, Igura T, Mochizuki K, et al. Pegylated interferon alpha-2b (Peg-IFN alpha-2b) affects early virologic response dose-dependently in patients with chronic hepatitis C genotype 1 during treatment with Peg-IFN alpha-2b plus ribavirin. J Viral Hepat. 2009;16:578–85.

    Article  PubMed  CAS  Google Scholar 

  15. Davis GL, Wong JB, McHutchison JG, Manns MP, Harvey J, Albrecht J. Early virologic response to treatment with peginterferon alfa-2b plus ribavirin in patients with chronic hepatitis C. Hepatology. 2003;38:645–52.

    Article  PubMed  CAS  Google Scholar 

  16. Toyoda H, Kumada T. Pharmacotherapy of chronic hepatitis C virus infection—the IDEAL trial: ‘2b or not 2b (=2a), that is the question’. Expert Opin Pharmacother. 2009;10:2845–57.

    Article  PubMed  CAS  Google Scholar 

  17. Akuta N, Suzuki F, Kawamura Y, Yatsuji H, Sezaki H, Suzuki Y, et al. Predictors of viral kinetics to peginterferon plus ribavirin combination therapy in Japanese patients infected with hepatitis C virus genotype 1b. J Med Virol. 2007;79:1686–95.

    Article  PubMed  CAS  Google Scholar 

  18. Nakagawa M, Sakamoto N, Ueyama M, Mogushi K, Nagaie S, Itsui Y, et al. Mutations in the interferon sensitivity determining region and virological response to combination therapy with pegylated-interferon alpha 2b plus ribavirin in patients with chronic hepatitis C-1b infection. J Gastroenterol. 2010;45:656–65.

    Article  PubMed  CAS  Google Scholar 

  19. Fellay J, Thompson AJ, Ge D, Gumbs CE, Urban TJ, Shianna KV, et al. ITPA gene variants protect against anaemia in patients treated for chronic hepatitis C. Nature. 2010;464:405–8.

    Article  PubMed  CAS  Google Scholar 

  20. El-Shamy A, Nagano-Fujii M, Sasase N, Imoto S, Kim SR, Hotta H. Sequence variation in hepatitis C virus nonstructural protein 5A predicts clinical outcome of pegylated interferon/ribavirin combination therapy. Hepatology. 2008;48:38–47.

    Article  PubMed  CAS  Google Scholar 

  21. Tanaka Y, Nishida N, Sugiyama M, Kurosaki M, Matsuura K, Sakamoto N, et al. Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. Nat Genet. 2009;41:1105–9.

    Article  PubMed  CAS  Google Scholar 

  22. Thomas DL, Thio CL, Martin MP, Qi Y, Ge D, O’Huigin C, et al. Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature. 2009;461:798–801.

    Article  PubMed  CAS  Google Scholar 

  23. Ge D, Fellay J, Thompson AJ, Simon JS, Shianna KV, Urban TJ, et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature. 2009;461:399–401.

    Article  PubMed  CAS  Google Scholar 

  24. Suppiah V, Moldovan M, Ahlenstiel G, Berg T, Weltman M, Abate ML, et al. IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy. Nat Genet. 2009;41:1100–4.

    Article  PubMed  CAS  Google Scholar 

  25. Melis R, Fauron C, McMillin G, Lyon E, Shirts B, Hubley LM, et al. Simultaneous genotyping of rs12979860 and rs8099917 variants near the IL28B locus associated with HCV clearance and treatment response. J Mol Diagn. 2011;13:446–51.

    Article  PubMed  CAS  Google Scholar 

  26. Muir AJ, Bornstein JD, Killenberg PG, Atlantic Coast Hepatitis Treatment Group. Peginterferon alfa-2b and ribavirin for the treatment of chronic hepatitis C in blacks and non-Hispanic whites. N Engl J Med. 2004;350:2265–71.

    Article  PubMed  CAS  Google Scholar 

  27. Okanoue T, Itoh Y, Hashimoto H, Yasui K, Minami M, Takehara T, et al. Predictive values of amino acid sequences of the core and NS5A regions in antiviral therapy for hepatitis C: a Japanese multi-center study. J Gastroenterol. 2009;44:952–63.

    Article  PubMed  CAS  Google Scholar 

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The authors declare that they have no conflict of interest.

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Correspondence to Shiho Miyase.

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Miyase, S., Haraoka, K., Ouchida, Y. et al. Randomized trial of peginterferon α-2a plus ribavirin versus peginterferon α-2b plus ribavirin for chronic hepatitis C in Japanese patients. J Gastroenterol 47, 1014–1021 (2012). https://doi.org/10.1007/s00535-012-0560-9

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  • DOI: https://doi.org/10.1007/s00535-012-0560-9

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