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Reducing Peg-IFN doses causes later virologic response or no response in HCV genotype 1 patients treated with Peg-IFN alfa-2b plus ribavirin

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

Background

The timing to the first undetectable hepatitis C virus (HCV) RNA level is strongly associated with sustained virologic response in pegylated interferon (Peg-IFN) plus ribavirin combination therapy for patients with chronic hepatitis C (CH-C) with genotype 1. This study was conducted to clarify the impact of drug exposure to Peg-IFN on the timing of HCV RNA negativity in Peg-IFN plus ribavirin combination therapy for CH-C patients with genotype 1.

Methods

A total of 1409 patients treated with Peg-IFN alfa-2b plus ribavirin were enrolled and classified into four categories according to the Peg-IFN dosage. Furthermore, 100 patients were extracted from each Peg-IFN dosage category to adjust for characteristic factors, using the propensity score method.

Results

Peg-IFN exposure was dose-dependently associated with the timing of HCV RNA negativity (p ≤ 0.001). The HCV RNA negative rate at week 4 decreased from 12% with a Peg-IFN dose of >1.5 μg/kg/week to 1–3% with a dose of <1.5 μg/kg/week (p ≤ 0.001), and at week 12 the rate had decreased from 44% with a dose of ≥1.2 μg/kg/week to 18% with a dose of <1.2 μg/kg/week (p = 0.001). Treatment failure (patients without a 1-log decrease of HCV RNA at week 4 or a 2-log decrease of HCV RNA at week 12, or positive at week 24) was found in 54–66% of patients given <1.2 μg/kg/week (p ≤ 0.001), and these patients accounted for 64% of the non-responders.

Conclusions

The timing of HCV RNA negativity depends significantly on the Peg-IFN dose. Reducing the Peg-IFN dose can induce a later virologic response or non-response in HCV genotype 1 patients treated with Peg-IFN plus ribavirin.

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Acknowledgments

Other institutions and participants in the Osaka Liver Forum are: Osaka Medical Center for Cancer and Cardiovascular Diseases, K Katayama and K Imanaka; Sumitomo Hospital, A Yamada; Itami City Hospital, T Kitada; Toyonaka Municipal Hospital, M Inada; Yao Municipal Hospital, H Fukui; Suita Municipal Hospital, T Nagase; NTT West Osaka Hospital, A Kaneko; National Hospital Organization Minami Wakayama Medical Center, K Fujimoto; Nishinomiya Municipal Central Hospital, H Ogawa; Saiseikai Senri Hospital, K Suzuki; Osaka Kaisei Hospital, N Imaizumi; Kano General Hospital, S Kubota; Saso Hospital, M Nishiuchi; and Meiwa Hospital, Y Hayakawa. This work was supported by a Grant-in-Aid for Research on Hepatitis and BSE from the Ministry of Health, Labour, and Welfare of Japan, and by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture of Japan.

Conflict of interest

Professor Tetsuo Takehara received scholarship funds from Merck Sharp & Dohme K. K. Co., Ltd, and Chugai Pharmaceutical Co., Ltd. Dr. Tatsuya Kanto has an affiliation with a donation-funded department from Merck Sharp & Dohme K. K. Co., Ltd.

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Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan

    Tsugiko Oze, Naoki Hiramatsu, Changho Song, Takayuki Yakushijin, Masanori Miyazaki, Atsushi Hosui, Takuya Miyagi, Yuichi Yoshida, Tomohide Tatsumi, Shinichi Kiso, Tatsuya Kanto, Akinori Kasahara & Tetsuo Takehara

  2. Higashiosaka City Central Hospital, Higashiosaka, Japan

    Sadaharu Iio

  3. Otemae Hospital, Osaka, Japan

    Yoshinobu Doi

  4. Osaka Police Hospital, Osaka, Japan

    Masahide Oshita

  5. Kansai Rosai Hospital, Amagasaki, Japan

    Hideki Hagiwara & Norio Hayashi

  6. National Hospital Organization Osaka National Hospital, Osaka, Japan

    Eiji Mita

  7. Osaka Koseinenkin Hospital, Osaka, Japan

    Toshifumi Ito

  8. Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Japan

    Yoshiaki Inui

  9. National Hospital Organization Osaka Minami Medical Center, Kawachinagano, Japan

    Taizo Hijioka

  10. Minoh City Hospital, Minoh, Japan

    Shinji Tamura

  11. Osaka Rosai Hospital, Sakai, Japan

    Harumasa Yoshihara

  12. Osaka General Medical Center, Osaka, Japan

    Atsuo Inoue

  13. Ikeda Municipal Hospital, Ikeda, Japan

    Yasuharu Imai

  14. Kinki Central Hospital of Mutual Aid Association of Public School Teachers, Itami, Japan

    Eijiro Hayashi

  15. National Hospital Organization Minami Wakayama Medical Center, Tanabe, Japan

    Michio Kato

Authors
  1. Tsugiko Oze
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  2. Naoki Hiramatsu
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  3. Changho Song
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  4. Takayuki Yakushijin
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  5. Sadaharu Iio
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  16. Yasuharu Imai
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  17. Eijiro Hayashi
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  19. Masanori Miyazaki
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  24. Shinichi Kiso
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  26. Akinori Kasahara
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  28. Tetsuo Takehara
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Corresponding author

Correspondence to Naoki Hiramatsu.

Additional information

T. Oze and N. Hiramatsu contributed equally to this work.

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Oze, T., Hiramatsu, N., Song, C. et al. Reducing Peg-IFN doses causes later virologic response or no response in HCV genotype 1 patients treated with Peg-IFN alfa-2b plus ribavirin. J Gastroenterol 47, 334–342 (2012). https://doi.org/10.1007/s00535-011-0498-3

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  • DOI: https://doi.org/10.1007/s00535-011-0498-3

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