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A population-based cohort study for the risk factors of HCC among hepatitis B virus mono-infected subjects in Japan

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

Background

There have only been a few prospective studies investigating risk factors associated with the development of hepatocellular carcinoma (HCC) among chronic hepatitis B patients all over the world, and no study has been conducted in Japanese population.

Methods

A population-based cohort consisting of 19393 subjects (middle aged or older) with over 13 years’ follow-up was investigated in Japan.

Results

Of 19393 subjects, 479 had hepatitis B virus (HBV) mono-infection (2.5%). During the 245923 person-years’ follow-up (average follow-up period 12.7 years), 13 cases of newly diagnosed HCC were documented in the HBV mono-infected group. Several factors at baseline (male, smoking, alanine aminotransferase, the positivity of HBe antigen and HB core-related antigen, the proportion of HBV DNA ≥ 5 log copies/mL, T1753V mutation, and A1762T/G1764A double mutation) were significantly associated with HCC among HBV mono-infected subjects. Multivariate-adjusted Cox hazard model showed that A1762T/G1764A (hazard ratio 7.05 [95% confidence interval (CI) 1.03–48.12, P = 0.046]) was the only independent risk factor for the development of HCC. Kaplan–Meier method also showed that the probability of HCC occurrence-free was significantly lower in HBV mono-infected subjects with A1762T/G1764A double mutation than those without these mutations.

Conclusion

HBV mono-infected subjects with A1762T/G1764A double mutation could be at high risk of HCC development during the natural course of HBV infection.

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Author information

Authors and Affiliations

  1. Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

    Atsunori Kusakabe, Shunsuke Nojiri & Takashi Joh

  2. Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Kawasumi, Mizuho, Nagoya, 467-8601, Japan

    Yasuhito Tanaka, Fuat Kurbanov & Kanako Tatematsu

  3. Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan

    Manami Inoue & Shoichiro Tsugane

  4. The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan

    Masashi Mizokami

Authors
  1. Atsunori Kusakabe
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  2. Yasuhito Tanaka
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  3. Manami Inoue
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  4. Fuat Kurbanov
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  5. Kanako Tatematsu
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  6. Shunsuke Nojiri
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  7. Takashi Joh
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  8. Shoichiro Tsugane
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  9. Masashi Mizokami
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Corresponding author

Correspondence to Yasuhito Tanaka.

Additional information

This article is authored in cooperation with the JPHC Study Group, members of which are listed in the Appendix.

The online version of the editorial referring to this article can be found under doi:10.1007/s00535-010-0314-5.

Appendix

Appendix

Members of the Japan Public Health Center-based Prospective Study (JPHC Study, principal investigator: S. Tsugane) Group are:

S. Tsugane, M. Inoue, T. Sobue, and T. Hanaoka, National Cancer Center, Tokyo; J. Ogata, S. Baba, T. Mannami, A. Okayama, and Y. Kokubo, National Cardiovascular Center, Osaka; K. Miyakawa, F. Saito, A. Koizumi, Y. Sano, I. Hashimoto, T. Ikuta, and Y. Tanaba, Iwate Prefectural Ninohe Public Health Center, Iwate; Y. Miyajima, N. Suzuki, S. Nagasawa, Y. Furusugi, and N. Nagai, Akita Prefectural Yokote Public Health Center, Akita; H. Sanada, Y. Hatayama, F. Kobayashi, H. Uchino, Y. Shirai, T. Kondo, R. Sasaki, Y. Watanabe, Y. Miyagawa, and Y. Kobayashi, Nagano Prefectural Saku Public Health Center, Nagano; Y. Kishimoto, E. Takara, T. Fukuyama, M. Kinjo, M. Irei, and H. Sakiyama, Okinawa Prefectural Chubu Public Health Center, Okinawa; K. Imoto, H. Yazawa, T. Seo, A. Seiko, F. Ito, F. Shoji and R. Saito, Katsushika Public Health Center, Tokyo; A. Murata, K. Minato, K. Motegi, and T. Fujieda, Ibaraki Prefectural Mito Public Health Center, Ibaraki; K. Matsui, T. Abe, M. Katagiri, and M. Suzuki, Niigata Prefectural Kashiwazaki and Nagaoka Public Health Center, Niigata; M. Doi, A. Terao, Y. Ishikawa, and T. Tagami, Kochi Prefectural Chuo-higashi Public Health Center, Kochi; H. Sueta, H. Doi, M. Urata, N. Okamoto, and F. Ide, Nagasaki Prefectural Kamigoto Public Health Center, Nagasaki; H. Sakiyama, N. Onga, H. Takaesu, and M. Uehara, Okinawa Prefectural Miyako Public Health Center, Okinawa; F. Horii, I. Asano, H. Yamaguchi, K. Aoki, S. Maruyama, M. Ichii, and M. Takano, Osaka Prefectural Suita Public Health Center, Osaka; Y. Tsubono, Tohoku University, Miyagi; K. Suzuki, Research Institute for Brain and Blood Vessels Akita, Akita; Y. Honda, K. Yamagishi, S. Sakurai, and N. Tsuchiya, Tsukuba University, Ibaraki; M. Kabuto, National Institute for Environmental Studies, Ibaraki; M. Yamaguchi, Y. Matsumura, S. Sasaki, and S. Watanabe, National Institute of Health and Nutrition, Tokyo; M. Akabane, Tokyo University of Agriculture, Tokyo; T. Kadowaki, Tokyo University, Tokyo; M. Noda and T. Mizoue, National Center for Global Health and Medicine, Tokyo; Y. Kawaguchi, Tokyo Medical and Dental University, Tokyo; Y. Takashima and M. Yoshida, Kyorin University, Tokyo; K. Nakamura, Niigata University, Niigata; S. Matsushima and S. Natsukawa, Saku General Hospital, Nagano; H. Shimizu, Sakihae Institute, Gifu; H. Sugimura, Hamamatsu University, Shizuoka; S. Tominaga, Aichi Cancer Center Research Institute, Aichi; H. Iso, Osaka University, Osaka; M. Iida, W. Ajiki, and A. Ioka, Osaka Medical Center for Cancer and Cardiovascular Disease, Osaka; S. Sato, Chiba Prefectural Institute of Public Heath, Chiba; E. Maruyama, Kobe University, Hyogo; M. Konishi, K. Okada, and I. Saito, Ehime University, Ehime; N. Yasuda, Kochi University, Kochi; S. Kono, Kyushu University, Fukuoka.

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Kusakabe, A., Tanaka, Y., Inoue, M. et al. A population-based cohort study for the risk factors of HCC among hepatitis B virus mono-infected subjects in Japan. J Gastroenterol 46, 117–124 (2011). https://doi.org/10.1007/s00535-010-0307-4

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  • DOI: https://doi.org/10.1007/s00535-010-0307-4

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