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Effects of long-term entecavir treatment on the incidence of hepatocellular carcinoma in chronic hepatitis B patients

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Abstract

Background and aim

Entecavir is one of the most-used nucleoside analogues for the treatment of patients with chronic hepatitis B virus (HBV) infection. The aim of this study was to clarify the effects of long-term entecavir treatment on the incidence of hepatocellular carcinoma (HCC).

Methods

The participants were 249 patients with chronic HBV infection who had been treated by entecavir for more than 2 years. Hepatic functional reserve and incidence of HCC were evaluated, and the factors that might contribute to the development of HCC were analyzed.

Results

Prothrombin activity was significantly elevated at 60 months after starting entecavir (from 85.9 ± 17.4 to 97.0 ± 16.9 %, p < 0.001). The albumin level was also significantly elevated at 60 months after starting entecavir (from 4.0 ± 0.5 to 4.3 ± 0.3 mg/dL, p < 0.001). The annual incidence of HCC decreased over time, and the incidence of HCC was only 1.8 % at 5 years after starting entecavir. On multivariate analysis for HCC incidence, older age and low platelet count were significant, independent contributing factors.

Conclusions

Long-term treatment with entecavir improved hepatic functional reserve and decreased the incidence of HCC over time after 3 years. To decrease the incidence of HCC, careful induction of long-term entecavir treatment in younger patients with chronic HBV infection and better hepatic functional reserve would be important.

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Compliance with Ethical Standards

Ethical approval

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008 (5). Informed consent for being included in the study was obtained from all patients. The Ethics Committee of Ehime University Hospital approved the study protocol (approval ID 0906003), which conformed to the ethical guidelines of the Declaration of Helsinki amended in 2008. Written, informed consent was obtained from each patient.

Conflict of interest

Takao Watanabe, Yoshio Tokumoto, Kouji Joko, Kojiro Michitaka, Toshie Mashiba, Atsushi Hiraoka, Hironori Ochi, Yohei Koizumi, Fujimasa Tada, Masashi Hirooka, Osamu Yoshida, Yusuke Imai, Masanori Abe and Yoichi Hiasa declare that they have no conflicts of interest (COI).

Author information

Authors and Affiliations

  1. Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan

    Takao Watanabe, Yoshio Tokumoto, Yohei Koizumi, Fujimasa Tada, Masashi Hirooka, Osamu Yoshida, Yusuke Imai, Masanori Abe & Yoichi Hiasa

  2. Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Bunkyocho 1, Matsuyama, Ehime, 790-8524, Japan

    Kouji Joko, Toshie Mashiba & Hironori Ochi

  3. Department of Gastroenterology, Ehime Prefectural Central Hospital, Kasugamachi 83, Matsuyama, Ehime, 790-0024, Japan

    Kojiro Michitaka & Atsushi Hiraoka

Authors
  1. Takao Watanabe
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  2. Yoshio Tokumoto
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  3. Kouji Joko
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  4. Kojiro Michitaka
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  7. Hironori Ochi
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  8. Yohei Koizumi
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  9. Fujimasa Tada
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  10. Masashi Hirooka
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  11. Osamu Yoshida
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  13. Masanori Abe
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  14. Yoichi Hiasa
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Corresponding author

Correspondence to Yoichi Hiasa.

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Watanabe, T., Tokumoto, Y., Joko, K. et al. Effects of long-term entecavir treatment on the incidence of hepatocellular carcinoma in chronic hepatitis B patients. Hepatol Int 10, 320–327 (2016). https://doi.org/10.1007/s12072-015-9647-8

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  • DOI: https://doi.org/10.1007/s12072-015-9647-8

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