α-Fetoprotein is a surrogate marker for predicting treatment failure in telaprevir-based triple combination therapy for genotype 1b chronic hepatitis C Japanese patients with the IL28B minor genotype

Authors

  • Noritomo Shimada,

    Corresponding author
    1. Division of Gastroenterology and Hepatology, Shinmatsudo Central General Hospital, Matsudo, Chiba, Japan
    • Correspondence to: Noritomo Shimada, MD, PhD, 1-380 Shinmatsudo, Matsudo, 270-0034 Chiba, Japan.

      E-mail: noritomos@jcom.home.ne.jp

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  • Akihito Tsubota,

    1. Institute of Clinical Medicine and Research, Jikei University School of Medicine, Kashiwa, Chiba, Japan
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  • Masanori Atsukawa,

    1. Department of Internal Medicine, Division of Gastroenterology, Nippon Medical School, Chiba Hokusoh Hospital, Inzai, Chiba, Japan
    2. Department of Internal Medicine, Division of Gastroenterology, Nippon Medical School, Bunkyou-ku, Tokyo, Japan
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  • Hiroshi Abe,

    1. Department of Internal Medicine, Division of Gastroenterology and Hepatology, Jikei University School of Medicine Katsushika Medical Center, Katsushika-ku, Tokyo, Japan
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  • Makiko Ika,

    1. Division of Gastroenterology and Hepatology, Shinmatsudo Central General Hospital, Matsudo, Chiba, Japan
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  • Keizo Kato,

    1. Division of Gastroenterology and Hepatology, Shinmatsudo Central General Hospital, Matsudo, Chiba, Japan
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  • Yoshiyuki Sato,

    1. Division of Gastroenterology and Hepatology, Shinmatsudo Central General Hospital, Matsudo, Chiba, Japan
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  • Chisa Kondo,

    1. Department of Internal Medicine, Division of Gastroenterology, Nippon Medical School, Chiba Hokusoh Hospital, Inzai, Chiba, Japan
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  • Choitsu Sakamoto,

    1. Department of Internal Medicine, Division of Gastroenterology, Nippon Medical School, Bunkyou-ku, Tokyo, Japan
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  • Yasuhito Tanaka,

    1. Department of Virology and Liver unit, Nagoya City University Graduate School of Medical Sciences, Mizuho, Nagoya, Japan
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  • Yoshio Aizawa

    1. Department of Internal Medicine, Division of Gastroenterology and Hepatology, Jikei University School of Medicine Katsushika Medical Center, Katsushika-ku, Tokyo, Japan
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Abstract

Even when treated with telaprevir-based triple therapy, some patients fail to achieve a sustained virological response. This study identified factors related closely to treatment failure. A total of 146 Japanese genotype 1b chronic hepatitis C patients were enrolled in this prospective, multicenter study and received a 24-week regimen of triple therapy. The end-of-treatment response rate was significantly lower in patients with the interleukin 28B (IL28B) (rs8099917) non-TT genotype (85.2%) than in those with the TT genotype (100%, P = 0.0002). Multiple logistic regression analysis identified high α-fetoprotein levels as an independent factor related to non-end-of-treatment response in patients with the non-TT genotype. A cut-off value of 20 ng/ml was determined for a non-end-of-treatment response; sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 75.0%, 95.7%, 75.0%, 75.0%, and 92.6%, respectively. Multiple logistic regression analysis for a sustained virological response identified the IL28B TT genotype, low α-fetoprotein levels, non-responders, and a rapid virological response. The sustained virological response rate was significantly lower in patients with the non-TT genotype (59.3%) than in those with the TT genotype (96.7%, P < 0.0001). In patients with the non-TT genotype, α-fetoprotein was the most significant predictor for non-sustained virological response by univariate analysis. A cut-off value of 7.4 ng/ml α-fetoprotein was determined for non-sustained virological response; sensitivity, specificity, PPV, NPV, and accuracy were 63.6%, 87.5%, 77.8%, 77.8%, and 77.8%, respectively. For the non-TT patients, serum α-fetoprotein levels may be a surrogate marker for predicting treatment failure in telaprevir-based therapy for genotype 1b chronic hepatitis C. J. Med. Virol. 86:461–472, 2014. © 2013 Wiley Periodicals, Inc.

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