J Gastroenterol. 2017 Jun 20. doi: 10.1007/s00535-017-1360-z. [Epub ahead of print]
Combinational use of hepatitis B viral antigens predicts responses to nucleos(t)ide analogue/peg-interferon sequential therapy.Matsumoto A1, Nishiguchi S2, Enomoto H2, Kang JH3, Tanaka Y4, Shinkai N4, Kurosaki M5, Enomoto M6, Kanda T7, Yokosuka O7, Yatsuhashi H8, Nagaoka S8, Okuse C9, Kagawa T10, Mine T10, Takaguchi K11, Saito S12, Hino K13, Ikeda F14, Sakisaka S15, Morihara D15, Miyase S16, Tsuge M17, Chayama K17, Hiramatsu N18, Suzuki Y19, Murata K20,21, Tanaka E22. Author information 1Department of Medicine, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, 390-8621, Japan.2Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.3Center for Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan.4Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.5Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.6Department of Hepatology, Osaka City University Medical School, Osaka, Japan.7Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan.8The Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Omura, Japan.9Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan.10Division of Gastroenterology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan.11Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan.12Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Yokohama, Japan.13Department of Hepatology and Pancreatology, Kawasaki Medical School, Kurashiki, Japan.14Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.15Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine, Fukuoka, Japan.16Department of Gastroenterology and Hepatology, Kumamoto Shinto General Hospital, Kumamoto, Japan.17Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.18Department of Gastroenterology, Osaka Rosai Hospital, Sakai, Japan.19Department of Hepatology, Toranomon Hospital, Tokyo, Japan.20The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan.21Department of Gastroenterology, Graduate School of Medical Sciences, International University of Health and Welfare, Narita, Japan.22Department of Medicine, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, 390-8621, Japan. [email protected].
AbstractBACKGROUND: 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.
KEYWORDS: Anti-viral therapy; Chronic hepatitis; Covalently closed circular DNA; Hepatitis B core-related antigen; Hepatitis B surface antigen
在peg-IFN完成后48周，二十六名患者（27％）被判断为应答者。基线因素分析显示，乙型肝炎表面抗原（HBsAg）<3.1 log IU / ml和HB核心相关抗原（HBcrAg）<3.9 log U / ml是治疗反应的显着指标。在peg-IFN治疗期间，应答者和非应答者的标记物水平都下降，但是在停止peg-IFN后，响应者继续下降。在响应判断时，较低的HBsAg（<2.0log IU / ml）和HBcrAg（<3.8log U / ml）水平也显着地与有利的反应相关。而在基线时，较低的HBcrAg是判断时HBcrAg水平降低的唯一预测因素，HBsAg降低，HBcrAg降低，并且在基线时使用阿德福韦酯可预测研究终点时HBsAg水平的降低。阿德福韦酯的使用也与较高的血清IFN-λ3相关，这可能有助于降低患者的HBsAg水平。
结论：