Akihiro Matsumoto1, Shuhei Nishiguchi2, Hirayuki Enomoto2, Yasuhito Tanaka3, Noboru Shinkai3, Chiaki Okuse4, Jong-Hon Kang5, Takeshi Matsui5, Shiho Miyase6, Hiroshi Yatsuhashi7, Shinya Nagaoka7, Tatsuo Kanda8, Masaru Enomoto9, Ryoko Yamada10, Naoki Hiramatsu11, Satoru Saito12, Koichi Takaguchi13, Kiyoaki Ito14, Tsutomu Masaki15, Daisuke Morihara16, Masataka Tsuge17, Kazuaki Chayama17, Fusao Ikeda18, Tatehiro Kagawa19, Yasuteru Kondo20, Kazumoto Murata21, Eiji Tanaka22. 1. Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan. 2. Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan. 3. Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. 4. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kawasaki Municipal Tama Hospital, Kawasaki, Japan. 5. Center for Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan. 6. Department of Gastroenterology and Hepatology, Kumamoto Shinto General Hospital, Kumamoto, Japan. 7. The Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Omura, Japan. 8. Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan. 9. Department of Hepatology, Osaka City University Medical School, Osaka, Japan. 10. Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. 11. Department of Gastroenterology, Osaka Rosai Hospital, Sakai, Japan. 12. Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Yokohama, Japan. 13. Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan. 14. Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Japan. 15. Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kagawa, Japan. 16. Department of Gastroenterology, Fukuoka University Faculty of Medicine, Fukuoka, Japan. 17. Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. 18. Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan. 19. Division of Gastroenterology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan. 20. Department of Hepatology, Sendai Kousei Hospital, Sendai, Japan. 21. Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimotsuke, Japan. 22. Department for the Promotion of Regional Medicine, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, 390-8621, Japan. etanaka@shinshu-u.ac.jp.
Abstract
BACKGROUND: A prospective pilot study of tenofovir disoproxil fumarate (TDF) and pegylated interferon alpha 2a (P-IFN) add-on therapy was conducted to evaluate its efficacy in reducing viral antigen levels in Japanese patients with chronic hepatitis B (UMIN 000020179). METHODS:Patients with chronic hepatitis B receiving maintenance TDF therapy and exhibiting hepatitis B surface antigen (HBsAg) level > 800 IU/ml were divided into two arms. P-IFN was added for 48 weeks in the add-on arm (n = 32), while TDF monotherapy was maintained in the control arm (n = 51). Both groups were followed for 96 weeks after baseline measurements. RESULTS: Almost all patients in the control arm displayed a slow and constant reduction in HBsAg during follow-up. In contrast, roughly half of the add-on arm exhibited a sharp decline in HBsAg during P-IFN administration, which disappeared after halting P-IFN. At 96 weeks after baseline, 41% (13/32) of patients in the add-on arm had shown a rapid decrease in HBsAg, versus 2% (1/51) in the control arm (p < 0.001). Add-on therapy and increased cytotoxic T-cell response were significant factors associated with a rapid decrease in HBsAg according to multivariate analysis. In addition, higher HB core-related antigen (HBcrAg) level at baseline (p = 0.001) and add-on therapy (p = 0.036) were significant factors associated with a rapid reduction in HBcrAg. CONCLUSIONS:TDF and P-IFN add-on therapy in Japanese patients with chronic hepatitis B facilitated rapid decreases in HBsAg and HBcrAg. Further studies are needed to improve early HBsAg clearance rate.
RCT Entities:
BACKGROUND: A prospective pilot study of tenofovir disoproxil fumarate (TDF) and pegylated interferon alpha 2a (P-IFN) add-on therapy was conducted to evaluate its efficacy in reducing viral antigen levels in Japanese patients with chronic hepatitis B (UMIN 000020179). METHODS:Patients with chronic hepatitis B receiving maintenance TDF therapy and exhibiting hepatitis B surface antigen (HBsAg) level > 800 IU/ml were divided into two arms. P-IFN was added for 48 weeks in the add-on arm (n = 32), while TDF monotherapy was maintained in the control arm (n = 51). Both groups were followed for 96 weeks after baseline measurements. RESULTS: Almost all patients in the control arm displayed a slow and constant reduction in HBsAg during follow-up. In contrast, roughly half of the add-on arm exhibited a sharp decline in HBsAg during P-IFN administration, which disappeared after halting P-IFN. At 96 weeks after baseline, 41% (13/32) of patients in the add-on arm had shown a rapid decrease in HBsAg, versus 2% (1/51) in the control arm (p < 0.001). Add-on therapy and increased cytotoxic T-cell response were significant factors associated with a rapid decrease in HBsAg according to multivariate analysis. In addition, higher HB core-related antigen (HBcrAg) level at baseline (p = 0.001) and add-on therapy (p = 0.036) were significant factors associated with a rapid reduction in HBcrAg. CONCLUSIONS:TDF and P-IFN add-on therapy in Japanese patients with chronic hepatitis B facilitated rapid decreases in HBsAg and HBcrAg. Further studies are needed to improve early HBsAg clearance rate.
Entities:
Keywords:
Add-on therapy; Hepatitis B core-related antigen; Hepatitis B surface antigen; Pegylated interferon; Tenofovir