Akihiro Matsumoto1, Shuhei Nishiguchi2, Hirayuki Enomoto2, Jong-Hon Kang3, Yasuhito Tanaka4, Noboru Shinkai4, Masayuki Kurosaki5, Masaru Enomoto6, Tatsuo Kanda7, Osamu Yokosuka7, Hiroshi Yatsuhashi8, Shinya Nagaoka8, Chiaki Okuse9, Tatehiro Kagawa10, Tetsuya Mine10, Koichi Takaguchi11, Satoru Saito12, Keisuke Hino13, Fusao Ikeda14, Shotaro Sakisaka15, Daisuke Morihara15, Shiho Miyase16, Masataka Tsuge17, Kazuaki Chayama17, Naoki Hiramatsu18, Yoshiyuki Suzuki19, Kazumoto Murata20,21, Eiji Tanaka22. 1. Department of Medicine, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, 390-8621, Japan. 2. Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan. 3. Center for Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan. 4. Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. 5. Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan. 6. Department of Hepatology, Osaka City University Medical School, Osaka, Japan. 7. Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan. 8. The Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Omura, Japan. 9. Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan. 10. Division of Gastroenterology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan. 11. Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan. 12. Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Yokohama, Japan. 13. Department of Hepatology and Pancreatology, Kawasaki Medical School, Kurashiki, Japan. 14. Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan. 15. Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine, Fukuoka, Japan. 16. Department of Gastroenterology and Hepatology, Kumamoto Shinto General Hospital, Kumamoto, Japan. 17. Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. 18. Department of Gastroenterology, Osaka Rosai Hospital, Sakai, Japan. 19. Department of Hepatology, Toranomon Hospital, Tokyo, Japan. 20. The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan. 21. Department of Gastroenterology, Graduate School of Medical Sciences, International University of Health and Welfare, Narita, Japan. 22. Department of Medicine, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, 390-8621, Japan. etanaka@shinshu-u.ac.jp.
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.
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.
Entities:
Keywords:
Anti-viral therapy; Chronic hepatitis; Covalently closed circular DNA; Hepatitis B core-related antigen; Hepatitis B surface antigen
Authors: Christian G Schüttler; Ulrike C Wend; Fabian M Faupel; P Nico Lelie; Wolfram H Gerlich Journal: J Clin Virol Date: 2010-02-01 Impact factor: 3.168
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Authors: Carla S Coffin; Scott K Fung; Fernando Alvarez; Curtis L Cooper; Karen E Doucette; Claire Fournier; Erin Kelly; Hin Hin Ko; Mang M Ma; Steven R Martin; Carla Osiowy; Alnoor Ramji; Edward Tam; Jean Pierre Villeneuve Journal: Can Liver J Date: 2018-12-25