Combinational use of hepatitis B viral antigens predicts responses to nucleos(t)ide analogue/peg-interferon sequential therapy

Akihiro Matsumoto, Shuhei Nishiguchi, Hirayuki Enomoto, Jong Hon Kang, Yasuhito Tanaka, Noboru Shinkai, Masayuki Kurosaki, Masaru Enomoto, Tatsuo Kanda, Osamu Yokosuka, Hiroshi Yatsuhashi, Shinya Nagaoka, Chiaki Okuse, Tatehiro Kagawa, Tetsuya Mine, Koichi Takaguchi, Satoru Saito, Keisuke Hino, Fusao Ikeda, Shotaro SakisakaDaisuke Morihara, Shiho Miyase, Masataka Tsuge, Kazuaki Chayama, Naoki Hiramatsu, Yoshiyuki Suzuki, Kazumoto Murata, Eiji Tanaka

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background: This prospective cohort study searched for factors associated with a response to nucleos(t)ide analogue/peg-interferon (NUC/peg-IFN) sequential therapy. Methods: A total of 95 patients with chronic hepatitis B being treated with NUCs were enrolled. Immediately following NUC cessation, peg-IFN was administered at 180 µg/dose weekly for 48 weeks. Results: Twenty-six patients (27%) were judged to be responders at 48 weeks after the completion of peg-IFN. Analysis of baseline factors revealed that hepatitis B surface antigen (HBsAg) <3.1 log IU/ml and HB core-related antigen (HBcrAg) <3.9 log U/ml were significant indicators of a treatment response. The levels of the markers decreased in both responders and non-responders during peg-IFN therapy but continued falling in responders only after halting peg-IFN. Lower HBsAg (<2.0 log IU/ml) and HBcrAg (<3.8 log U/ml) levels at the time of response judgment were also significantly associated with a favorable response. While lower HBcrAg at baseline was the sole predictor of decreased HBcrAg levels at judgment, lower HBsAg, lower HBcrAg, and the use of adefovir dipivoxil at baseline predicted decreased HBsAg levels at the study endpoint. The use of adefovir dipivoxil was also associated with higher serum IFN-λ3, which might have contributed to the reduction in patient HBsAg levels. Conclusions: The combinational use of HBsAg and HBcrAg levels at baseline and their changes throughout sequential therapy may be useful for predicting a response to NUC/peg-IFN sequential therapy.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalJournal of Gastroenterology
DOIs
Publication statusAccepted/In press - Jun 20 2017

Fingerprint

Hepatitis B Antigens
Viral Antigens
Hepatitis B Surface Antigens
Interferons
Antigens
Therapeutics
Accidental Falls
Chronic Hepatitis B
Statistical Factor Analysis
Cohort Studies
Prospective Studies
Serum

Keywords

  • Anti-viral therapy
  • Chronic hepatitis
  • Covalently closed circular DNA
  • Hepatitis B core-related antigen
  • Hepatitis B surface antigen

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Combinational use of hepatitis B viral antigens predicts responses to nucleos(t)ide analogue/peg-interferon sequential therapy. / Matsumoto, Akihiro; Nishiguchi, Shuhei; Enomoto, Hirayuki; Kang, Jong Hon; Tanaka, Yasuhito; Shinkai, Noboru; Kurosaki, Masayuki; Enomoto, Masaru; Kanda, Tatsuo; Yokosuka, Osamu; Yatsuhashi, Hiroshi; Nagaoka, Shinya; Okuse, Chiaki; Kagawa, Tatehiro; Mine, Tetsuya; Takaguchi, Koichi; Saito, Satoru; Hino, Keisuke; Ikeda, Fusao; Sakisaka, Shotaro; Morihara, Daisuke; Miyase, Shiho; Tsuge, Masataka; Chayama, Kazuaki; Hiramatsu, Naoki; Suzuki, Yoshiyuki; Murata, Kazumoto; Tanaka, Eiji.

In: Journal of Gastroenterology, 20.06.2017, p. 1-11.

Research output: Contribution to journalArticle

Matsumoto, A, Nishiguchi, S, Enomoto, H, Kang, JH, Tanaka, Y, Shinkai, N, Kurosaki, M, Enomoto, M, Kanda, T, Yokosuka, O, Yatsuhashi, H, Nagaoka, S, Okuse, C, Kagawa, T, Mine, T, Takaguchi, K, Saito, S, Hino, K, Ikeda, F, Sakisaka, S, Morihara, D, Miyase, S, Tsuge, M, Chayama, K, Hiramatsu, N, Suzuki, Y, Murata, K & Tanaka, E 2017, 'Combinational use of hepatitis B viral antigens predicts responses to nucleos(t)ide analogue/peg-interferon sequential therapy', Journal of Gastroenterology, pp. 1-11. https://doi.org/10.1007/s00535-017-1360-z
Matsumoto, Akihiro ; Nishiguchi, Shuhei ; Enomoto, Hirayuki ; Kang, Jong Hon ; Tanaka, Yasuhito ; Shinkai, Noboru ; Kurosaki, Masayuki ; Enomoto, Masaru ; Kanda, Tatsuo ; Yokosuka, Osamu ; Yatsuhashi, Hiroshi ; Nagaoka, Shinya ; Okuse, Chiaki ; Kagawa, Tatehiro ; Mine, Tetsuya ; Takaguchi, Koichi ; Saito, Satoru ; Hino, Keisuke ; Ikeda, Fusao ; Sakisaka, Shotaro ; Morihara, Daisuke ; Miyase, Shiho ; Tsuge, Masataka ; Chayama, Kazuaki ; Hiramatsu, Naoki ; Suzuki, Yoshiyuki ; Murata, Kazumoto ; Tanaka, Eiji. / Combinational use of hepatitis B viral antigens predicts responses to nucleos(t)ide analogue/peg-interferon sequential therapy. In: Journal of Gastroenterology. 2017 ; pp. 1-11.
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abstract = "Background: This prospective cohort study searched for factors associated with a response to nucleos(t)ide analogue/peg-interferon (NUC/peg-IFN) sequential therapy. Methods: A total of 95 patients with chronic hepatitis B being treated with NUCs were enrolled. Immediately following NUC cessation, peg-IFN was administered at 180 µg/dose weekly for 48 weeks. Results: Twenty-six patients (27{\%}) were judged to be responders at 48 weeks after the completion of peg-IFN. Analysis of baseline factors revealed that hepatitis B surface antigen (HBsAg) <3.1 log IU/ml and HB core-related antigen (HBcrAg) <3.9 log U/ml were significant indicators of a treatment response. The levels of the markers decreased in both responders and non-responders during peg-IFN therapy but continued falling in responders only after halting peg-IFN. Lower HBsAg (<2.0 log IU/ml) and HBcrAg (<3.8 log U/ml) levels at the time of response judgment were also significantly associated with a favorable response. While lower HBcrAg at baseline was the sole predictor of decreased HBcrAg levels at judgment, lower HBsAg, lower HBcrAg, and the use of adefovir dipivoxil at baseline predicted decreased HBsAg levels at the study endpoint. The use of adefovir dipivoxil was also associated with higher serum IFN-λ3, which might have contributed to the reduction in patient HBsAg levels. Conclusions: The combinational use of HBsAg and HBcrAg levels at baseline and their changes throughout sequential therapy may be useful for predicting a response to NUC/peg-IFN sequential therapy.",
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T1 - Combinational use of hepatitis B viral antigens predicts responses to nucleos(t)ide analogue/peg-interferon sequential therapy

AU - Matsumoto, Akihiro

AU - Nishiguchi, Shuhei

AU - Enomoto, Hirayuki

AU - Kang, Jong Hon

AU - Tanaka, Yasuhito

AU - Shinkai, Noboru

AU - Kurosaki, Masayuki

AU - Enomoto, Masaru

AU - Kanda, Tatsuo

AU - Yokosuka, Osamu

AU - Yatsuhashi, Hiroshi

AU - Nagaoka, Shinya

AU - Okuse, Chiaki

AU - Kagawa, Tatehiro

AU - Mine, Tetsuya

AU - Takaguchi, Koichi

AU - Saito, Satoru

AU - Hino, Keisuke

AU - Ikeda, Fusao

AU - Sakisaka, Shotaro

AU - Morihara, Daisuke

AU - Miyase, Shiho

AU - Tsuge, Masataka

AU - Chayama, Kazuaki

AU - Hiramatsu, Naoki

AU - Suzuki, Yoshiyuki

AU - Murata, Kazumoto

AU - Tanaka, Eiji

PY - 2017/6/20

Y1 - 2017/6/20

N2 - Background: This prospective cohort study searched for factors associated with a response to nucleos(t)ide analogue/peg-interferon (NUC/peg-IFN) sequential therapy. Methods: A total of 95 patients with chronic hepatitis B being treated with NUCs were enrolled. Immediately following NUC cessation, peg-IFN was administered at 180 µg/dose weekly for 48 weeks. Results: Twenty-six patients (27%) were judged to be responders at 48 weeks after the completion of peg-IFN. Analysis of baseline factors revealed that hepatitis B surface antigen (HBsAg) <3.1 log IU/ml and HB core-related antigen (HBcrAg) <3.9 log U/ml were significant indicators of a treatment response. The levels of the markers decreased in both responders and non-responders during peg-IFN therapy but continued falling in responders only after halting peg-IFN. Lower HBsAg (<2.0 log IU/ml) and HBcrAg (<3.8 log U/ml) levels at the time of response judgment were also significantly associated with a favorable response. While lower HBcrAg at baseline was the sole predictor of decreased HBcrAg levels at judgment, lower HBsAg, lower HBcrAg, and the use of adefovir dipivoxil at baseline predicted decreased HBsAg levels at the study endpoint. The use of adefovir dipivoxil was also associated with higher serum IFN-λ3, which might have contributed to the reduction in patient HBsAg levels. Conclusions: The combinational use of HBsAg and HBcrAg levels at baseline and their changes throughout sequential therapy may be useful for predicting a response to NUC/peg-IFN sequential therapy.

AB - Background: This prospective cohort study searched for factors associated with a response to nucleos(t)ide analogue/peg-interferon (NUC/peg-IFN) sequential therapy. Methods: A total of 95 patients with chronic hepatitis B being treated with NUCs were enrolled. Immediately following NUC cessation, peg-IFN was administered at 180 µg/dose weekly for 48 weeks. Results: Twenty-six patients (27%) were judged to be responders at 48 weeks after the completion of peg-IFN. Analysis of baseline factors revealed that hepatitis B surface antigen (HBsAg) <3.1 log IU/ml and HB core-related antigen (HBcrAg) <3.9 log U/ml were significant indicators of a treatment response. The levels of the markers decreased in both responders and non-responders during peg-IFN therapy but continued falling in responders only after halting peg-IFN. Lower HBsAg (<2.0 log IU/ml) and HBcrAg (<3.8 log U/ml) levels at the time of response judgment were also significantly associated with a favorable response. While lower HBcrAg at baseline was the sole predictor of decreased HBcrAg levels at judgment, lower HBsAg, lower HBcrAg, and the use of adefovir dipivoxil at baseline predicted decreased HBsAg levels at the study endpoint. The use of adefovir dipivoxil was also associated with higher serum IFN-λ3, which might have contributed to the reduction in patient HBsAg levels. Conclusions: The combinational use of HBsAg and HBcrAg levels at baseline and their changes throughout sequential therapy may be useful for predicting a response to NUC/peg-IFN sequential therapy.

KW - Anti-viral therapy

KW - Chronic hepatitis

KW - Covalently closed circular DNA

KW - Hepatitis B core-related antigen

KW - Hepatitis B surface antigen

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