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The virological response in Koreans infected with HCV genotype 1 did not differ between groups treated with a full dose or reduced dose (≥80 % full dose) of peginterferon alfa-2a: a prospective randomized multicenter trial

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Abstract

Purpose

A high rate of sustained viral response (SVR) in Koreans with chronic hepatitis C (CHC) is related to a favorable IL28B genotype. We compared two dosing strategies for peginterferon alfa-2a in Koreans with CHC and defined the combined effect of polymorphisms and dosing on the virological response.

Methods

A total of 178 treatment-naïve patients with CHC genotype 1 were prospectively enrolled. All patients were randomly assigned to treatment with one of two peginterferon alfa-2a regimens: 180 μg per week for 48 weeks (full-dose group) or 180 μg per week during the first 12 weeks followed by 135 μg per week for the next 36 weeks (dose-reduction group). Polymorphisms related to IL28B, ITPA, C20orf194 and SLC29A1 were studied.

Results

SVR rates did not differ between the full-dose and dose-reduction groups (56.5 and 51.2 %, respectively, p = 0.474). The frequency of additional reductions of the peginterferon dose because of adverse events was higher in the full-dose group than in the dose-reduction group. SVR rates in patients homozygous for the IL28B major allele were higher than those in patients for the other IL28B alleles. For patients with unfavorable IL28B genotypes, SVR was less likely to be achieved in the dose-reduction group than in the full-dose group.

Conclusions

In Koreans with HCV genotype 1, the virological response to treatment did not differ between a full dose and reduced dose (≥80 % of full dose) of peginterferon alfa-2a. However, in the patients with unfavorable IL28B genotypes, the full-dose treatment of peginterferon alfa-2a may be beneficial.

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Abbreviations

HCV:

Hepatitis C virus

SVR:

Sustained viral response

SNP:

Single nucleotide polymorphism

IL28B:

Interleukin 28B

ITPA:

Inosine triphophatase

CHC:

Chronic hepatitis C

RVR:

Rapid virologic response

EVR:

Early virologic response

LD:

Linkage-disequlibrium

ETVR:

End of treatment response

ITT:

Intention to treatment

PP:

Per protocol

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Acknowledgements

Kwon JH, Bae SH, Lee YJ planned the study design and analyzed and interpreted the data. JH Kwon drafted the manuscript. HY Yim supported the randomization of patients and statistical analysis. YJ Lee, JG Shin and JS Choi performed the SNP study. All the authors prospectively enrolled and treated patients and acquired the data. All authors had access to the study data and reviewed and approved the final manuscript. This study was supported by a grant from the research supporting program of the Korean Association for the Study of the Liver.

Conflict of interest

Jung Hyun Kwon, Si Hyun Bae, Youn Jae Lee, Jin-Woo Lee, Young Seok Kim, Jae Seok Hwang, Won Young Tak, Jeong Won Jang, Byung Seok Lee, June Sung Lee, Chun Kyon Lee, Soon Koo Baik, Neung Hwa Park, Tae Hee Lee, Dong Joon Kim, Jae-Seok Choi, Jae-Gook Shin and Hyeon Woo Yim declare that they have no conflict of interest.

Ethical standard

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and the Helsinki Declaration of 1975, as revised in 2008. Informed consent was obtained from all patients for inclusion in the study.

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Authors and Affiliations

  1. Department of Internal Medicine, Incheon St. Mary’s Hospital, The Catholic University of Korea, Incheon, Korea

    Jung Hyun Kwon

  2. Department of Internal Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul, 137-040, Korea

    Si Hyun Bae & Jeong Won Jang

  3. Department of Internal Medicine, Pusan Paik Hospital, Inje University of Korea, Gaegum-dong 633-165, Busanjin-gu, Pusan, 614-735, Korea

    Youn Jae Lee

  4. Department of Internal Medicine, Inha University School of Medicine, Incheon, Korea

    Jin-Woo Lee

  5. Department of Internal Medicine, Bucheon Soonchunhyang Hospital, Soonchunhyang University of Korea, Bucheon, Korea

    Young Seok Kim

  6. Department of Internal Medicine, Dongsan Hospital, Keimyung University of Korea, Taegu, Korea

    Jae Seok Hwang

  7. Department of Internal Medicine, Kyungpook National University Hospital, Kyungpook National University of Korea, Taegu, Korea

    Won Young Tak

  8. Department of Internal Medicine, Chungnam National University Hospital, Chungnam National University of Korea, Taejon, Korea

    Byung Seok Lee

  9. Department of Internal Medicine, Ilsan Paik Hospital, Inje University of Korea, Ilsan, Korea

    June Sung Lee

  10. Department of Internal Medicine, National Health Insurance Corporation Ilsan Hospital, Ilsan, Korea

    Chun Kyon Lee

  11. Department of Internal Medicine, Wonju Christian Hospital, Yonsei University of Korea, Wonju, Korea

    Soon Koo Baik

  12. Department of Internal Medicine, Ulsan University Hospital, Ulsan University of Korea, Ulsan, Korea

    Neung Hwa Park

  13. Department of Internal Medicine, Konyang University Hospital, Konyang University of Korea, Taejon, Korea

    Tae Hee Lee

  14. Department of Internal Medicine, Chuncheon Sacred Heart Hospital, Hallym University of Korea, Chuncheon, Korea

    Dong Joon Kim

  15. Department of Pharmacology and PharmacoGenomics Research Center, Inje University of Korea, Pusan, Korea

    Jae-Seok Choi & Jae-Gook Shin

  16. Department of Clinical Pharmacology, Busan Paik Hospital, Inje University of Korea, Pusan, Korea

    Jae-Gook Shin

  17. Clinical Research Coordinating Center for Catholic Medical Center, The Catholic University of Korea, Seoul, Korea

    Hyeon Woo Yim

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  1. Jung Hyun Kwon
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  2. Si Hyun Bae
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  14. Tae Hee Lee
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  15. Dong Joon Kim
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  16. Jae-Seok Choi
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  17. Jae-Gook Shin
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  18. Hyeon Woo Yim
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Corresponding authors

Correspondence to Si Hyun Bae or Youn Jae Lee.

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Kwon, J.H., Bae, S.H., Lee, Y.J. et al. The virological response in Koreans infected with HCV genotype 1 did not differ between groups treated with a full dose or reduced dose (≥80 % full dose) of peginterferon alfa-2a: a prospective randomized multicenter trial. Hepatol Int 7, 1000–1009 (2013). https://doi.org/10.1007/s12072-013-9472-x

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  • DOI: https://doi.org/10.1007/s12072-013-9472-x

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