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Journal of Gastroenterology
February 2018, Volume 53, Issue 2, pp 247–257 | Cite as
Combinational use of hepatitis B viral antigens predicts responses to nucleos(t)ide analogue/peg-interferon sequential therapy
Authors
Authors and affiliations
Akihiro MatsumotoShuhei NishiguchiHirayuki EnomotoJong-Hon KangYasuhito TanakaNoboru ShinkaiMasayuki KurosakiMasaru EnomotoTatsuo KandaOsamu YokosukaHiroshi YatsuhashiShinya NagaokaChiaki OkuseTatehiro KagawaTetsuya MineKoichi TakaguchiSatoru SaitoKeisuke HinoFusao IkedaShotaro SakisakaDaisuke MoriharaShiho MiyaseMasataka TsugeKazuaki ChayamaNaoki HiramatsuYoshiyuki SuzukiKazumoto MurataEiji TanakaEmail author
Akihiro Matsumoto
1
Shuhei Nishiguchi
2
Hirayuki Enomoto
2
Jong-Hon Kang
3
Yasuhito Tanaka
4
Noboru Shinkai
4
Masayuki Kurosaki
5
Masaru Enomoto
6
Tatsuo Kanda
7
Osamu Yokosuka
7
Hiroshi Yatsuhashi
8
Shinya Nagaoka
8
Chiaki Okuse
9
Tatehiro Kagawa
10
Tetsuya Mine
10
Koichi Takaguchi
11
Satoru Saito
12
Keisuke Hino
13
Fusao Ikeda
14
Shotaro Sakisaka
15
Daisuke Morihara
15
Shiho Miyase
16
Masataka Tsuge
17
Kazuaki Chayama
17
Naoki Hiramatsu
18
Yoshiyuki Suzuki
19
Kazumoto Murata
2021
Eiji Tanaka
1Email authorView author's OrcID profile
1.Department of MedicineShinshu University School of MedicineMatsumotoJapan
2.Division of Hepatobiliary and Pancreatic Disease, Department of Internal MedicineHyogo College of MedicineNishinomiyaJapan
3.Center for GastroenterologyTeine Keijinkai HospitalSapporoJapan
4.Department of Virology and Liver UnitNagoya City University Graduate School of Medical SciencesNagoyaJapan
5.Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
6.Department of HepatologyOsaka City University Medical SchoolOsakaJapan
7.Department of Gastroenterology and Nephrology, Graduate School of MedicineChiba UniversityChibaJapan
8.The Clinical Research CenterNational Hospital Organization Nagasaki Medical CenterOmuraJapan
9.Division of Gastroenterology and Hepatology, Department of Internal MedicineSt. Marianna University School of MedicineKawasakiJapan
10.Division of Gastroenterology, Department of Internal MedicineTokai University School of MedicineIseharaJapan
11.Department of HepatologyKagawa Prefectural Central HospitalTakamatsuJapan
12.Department of Gastroenterology and HepatologyYokohama City University School of MedicineYokohamaJapan
13.Department of Hepatology and PancreatologyKawasaki Medical SchoolKurashikiJapan
14.Department of Gastroenterology and HepatologyOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesOkayamaJapan
15.Department of Gastroenterology and MedicineFukuoka University Faculty of MedicineFukuokaJapan
16.Department of Gastroenterology and HepatologyKumamoto Shinto General HospitalKumamotoJapan
17.Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health SciencesHiroshima UniversityHiroshimaJapan
18.Department of GastroenterologyOsaka Rosai HospitalSakaiJapan
19.Department of HepatologyToranomon HospitalTokyoJapan
20.The Research Center for Hepatitis and ImmunologyNational Center for Global Health and MedicineIchikawaJapan
21.Department of Gastroenterology, Graduate School of Medical SciencesInternational University of Health and WelfareNaritaJapan
Original Article—Liver, Pancreas, and Biliary Tract
First Online: 20 June 2017
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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.
Keywords
Hepatitis B surface antigen Hepatitis B core-related antigen Covalently closed circular DNA Chronic hepatitis Anti-viral therapy
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