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Predictive value of the IFNL4 polymorphism on outcome of telaprevir, peginterferon, and ribavirin therapy for older patients with genotype 1b chronic hepatitis C

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

Background

Older patients with chronic hepatitis C have a lower virological response to interferon (IFN) treatment compared to younger patients. The efficacy of telaprevir (TVR) and PEG-IFN plus ribavirin combination therapy and the predictive value of recently identified IFN lambda (IFNL) 4 polymorphisms on the outcome of therapy for older patients have not been addressed.

Methods

We assessed predictive factors for sustained virological response (SVR) to triple therapy in 226 younger (≤65 years) and 87 older (>65 years) Japanese patients with chronic genotype 1 hepatitis C. IFNL4 polymorphism ss469415590 was analyzed by Invader assay.

Results

The SVR rate for older patients was slightly lower than for younger patients (69 vs. 82 %, P = 0.043). In the older group, the SVR rate for patients with the IFNL4 TT/TT genotype was significantly higher than patients with TT/ΔG or ΔG/ΔG genotypes (81.8 and 42.9 %, P = 0.003). In multivariate regression analysis, rapid virological response (OR 36.601, P = 0.002) and IFNL4 TT/TT genotype (OR 19.502, P = 0.009) were identified as significant independent predictors for SVR in older patients. Treatment-related decreases in hemoglobin and increases in serum creatinine were higher in older patients than younger patients. Reduction of initial TVR dose to 1,500 mg per day alleviated these adverse events without compromising SVR rate in older patients.

Conclusions

Analysis of IFNL4 polymorphisms is a valuable predictor in older patients receiving TVR triple therapy. 1,500 mg per day is a suitable initial TVR dose for older Japanese patients.

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Acknowledgments

This work was supported by Grants-in-Aid for scientific research and development from the Ministry of Health, Labor and Welfare and the Ministry of Education, Culture, Sports, Science, and Technology, Government of Japan. The funders had no role in the study's design, data collection and analysis, the decision to publish, or preparation of the manuscript. No additional external funding was received for this study.

The authors thank the other members of the SNP Research Center for assistance with various aspects of this study. Part of this work was carried out at the Analysis Center of Life Science, Hiroshima University. Hiroshima Liver Study Group. Members of the Hiroshima Liver Study Group (listed in alphabetical order) include Shiomi Aimitsu (Hiroshima General Hospital of West Japan Railway Company, Hiroshima, Japan), Yasuyuki Aisaka (Hiroshima Red Cross Hospital, Hiroshima, Japan), Hajime Amano (Onomichi General Hospital, Hiroshima, Japan), Tatsuya Amimoto (Amimoto Clinic, Hiroshima, Japan), Keiko Arataki (Hiroshimakinen Hospital, Hiroshima, Japan), Nobuyuki Asada (Asada Clinic, Hiroshima, Japan), Takahiro Azakami (Miyoshi Cyuo Hospital, Hiroshima, Japan), Kunio Ishida (Hiroshima General Hospital, Hiroshima, Japan), Hiroto Ishihara (Hiroshima-Nishi Medical Center, Hiroshima, Japan), Tomokazu Ishitobi (Hiroshima Chuden Hospital, Hiroshima, Japan), Hiroyuki Ito (Saiseikai Kure Hospital, Hiroshima, Japan), Koji Kamada (Shobara Red Cross Hospital, Hiroshima, Japan), Masaya Kamiyasu (Kamiyasu Clinic, Hiroshima, Japan), Hiroiku Kawakami (Kawakami Clinic, Hiroshima, Japan), Shinsuke Kira (Saiseikai Hiroshima Hospital, Hiroshima, Japan), Mikiya Kitamoto (Hiroshima Prefectural Hospital, Hiroshima, Japan), Hideaki Kodama (Hiroshima Kinen Hospital, Hiroshima, Japan), Hiroshi Kohno (Kure Medical Center, Hiroshima, Japan), Hirotaka Kohno (Kure Medical Center, Hiroshima, Japan), Toshiyuki Masanaga (Masanaga Clinic, Hiroshima, Japan), Toshio Miura (Akitsu Prefectural Hospital, Hiroshima, Japan), Nami Mori (Hiroshima Red Cross Hospital, Hiroshima, Japan), Takashi Moriya (Chugoku Rousai Hospital, Hiroshima, Japan), Yutaka Nabeshima (Chuden Hospital, Hiroshima, Japan), Yuko Nagaoki (Higashihiroshima Medical Center, Hiroshima, Japan), Toshio Nakamura (Nakamura Clinic, Hiroshima, Japan), Toshio Nakanishi (Miyoshi Cyuo Hospital, Hiroshima, Japan), Ryo Nakashio (Nakashio Clinic, Hiroshima, Japan), Michihiro Nonaka (Hiroshima General Hospital, Hiroshima, Japan), Makoto Ohbayashi (Onomichi General Hospital, Hiroshima, Japan), Shintaro Takaki (Hiroshima Red Cross Hospital, Hiroshima, Japan), Eichi Takesaki (Higashihiroshima Medical Center, Hiroshima, Japan), Toru Tamura (Mazda Hospital, Hiroshima, Japan), Keiji Tsuji (Hiroshima City Asa Hospital, Hiroshima, Japan), Koji Waki (Hiroshima City Asa Hospital, Hiroshima, Japan), Masashi Watanabe (Kuchiwa Clinic, Hiroshima, Japan), Syuji Yamaguchi (Kure Kyosai Hospital, Hiroshima, Japan), Keitaro Yamashina (Hiroshima General Hospital of West Japan Railway Company, Hiroshima, Japan).

Conflict of interest

K Chayama received research grants from MSD K.K., Chugai Pharmaceutical Co., Ltd., Bristol-Myers Squibb Company, Mitsubishi Tanabe Pharma Corporation, Dainippon Sumitomo Pharma Co., Ltd., DAIICHI SANKYO COMPANY, LIMITED, Meiji Seika Pharma Co., Ltd., and received lecture fees from MSD K.K., Chugai Pharmaceutical Co., Ltd., Bristol-Myers Squibb Company, Mitsubishi Tanabe Pharma Corporation, Dainippon Sumitomo Pharma Co., Ltd.

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Authors and Affiliations

  1. Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan

    Hatsue Fujino, Michio Imamura, Yuko Nagaoki, Yoshiiku Kawakami, Hiromi Abe, C. Nelson Hayes, Hiromi Kan, Takayuki Fukuhara, Tomoki Kobayashi, Keiichi Masaki, Atsushi Ono, Takashi Nakahara, Youji Honda, Noriaki Naeshiro, Ayako Urabe, Satoe Yokoyama, Daisuke Miyaki, Eisuke Murakami, Tomokazu Kawaoka, Nobuhiko Hiraga, Masataka Tsuge, Akira Hiramatsu, Hideyuki Hyogo, Hiroshi Aikata, Shoichi Takahashi & Kazuaki Chayama

  2. Laboratory for Digestive Diseases, Center for Genomic Medicine, The Institute of Physical and Chemical Research (RIKEN), Hiroshima, Japan

    Daiki Miki, Hidenori Ochi & Kazuaki Chayama

  3. Department of Clinical Studies, Radiation Effects Research Foundation, Hiroshima, Japan

    Waka Ohishi

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  1. Hatsue Fujino
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  2. Michio Imamura
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  29. Kazuaki Chayama
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Hiroshima Liver Study Group

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Correspondence to Kazuaki Chayama.

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Fujino, H., Imamura, M., Nagaoki, Y. et al. Predictive value of the IFNL4 polymorphism on outcome of telaprevir, peginterferon, and ribavirin therapy for older patients with genotype 1b chronic hepatitis C. J Gastroenterol 49, 1548–1556 (2014). https://doi.org/10.1007/s00535-013-0924-9

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  • DOI: https://doi.org/10.1007/s00535-013-0924-9

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