Satoshi Mochida1, Masamitsu Nakao2, Nobuaki Nakayama2, Yoshihito Uchida2, Sumiko Nagoshi2, Akio Ido3, Toshihide Mimura4, Masayoshi Harigai5, Hiroshi Kaneko6, Hiroko Kobayashi7, Tetsuya Tsuchida8, Hiromichi Suzuki9, Nobuyuki Ura10, Yuichi Nakamura11, Masami Bessho11, Kazuo Dan12, Shigeru Kusumoto13, Yasutsuna Sasaki14, Hirofumi Fujii15, Fumitaka Suzuki16, Kenji Ikeda16, Kazuhiko Yamamoto17, Hajime Takikawa18, Hirohito Tsubouchi3, Masashi Mizokami19. 1. Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-cho, Iruma-gun, Saitama, 350-0495, Japan. smochida@saitama-med.ac.jp. 2. Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-cho, Iruma-gun, Saitama, 350-0495, Japan. 3. Department of Digestive and Lifestyle Related Diseases, Human and Enviromental Sciences, Health Research, Kagoshima University Graduate School of Medicine and Dental Sciences, Kagoshima, Japan. 4. Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University, Saitama, Japan. 5. Department of Pharmacovigilance, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan. 6. Division of Rheumatic Diseases, National Center for Global Health and Medicine, Tokyo, Japan. 7. Department of Gastroenterology and Rheumatology, School of Medicine, Fukushima Medical University, Fukushima, Japan. 8. Department of Dermatology, Saitama Medical University, Saitama, Japan. 9. Department of Nephrology, Saitama Medical University, Saitama, Japan. 10. Department of Nephrology, Teine Keijinkai Hospital, Sapporo, Japan. 11. Department of Hematology, Saitama Medical University, Saitama, Japan. 12. Department of Hematology, Nippon Medical School, Tokyo, Japan. 13. Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Science, Nagoya, Japan. 14. Department of Medical Oncology, International Medical Cnter/Comprehensive Cancer Center, Saitama Medical University, Saitama, Japan. 15. Department of Clinical Oncology, Jichi Medical University, Shimotsuke, Japan. 16. Department of Hepatology, Toranomon Hospital, Tokyo, Japan. 17. Department of Allergy and Pheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. 18. Department of Medicine, Teikyo University of School of Medicine, Tokyo, Japan. 19. The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan.
Abstract
BACKGROUND: The significance of HBV reactivation during immunosuppressive therapy was evaluated in three nationwide cohorts including patients with previously resolved HBV (prHBV) infection. METHODS: The clinical features of 1061 patients with acute liver failure (ALF) or late-onset hepatic failure (LOHF) were retrospectively examined, focusing on those who experienced HBV reactivation. Additionally, 420 patients with prHBV infection were prospectively enrolled: 203 received immunosuppressive therapies immediately after enrollment, while the remaining 217 were enrolled after having received immunosuppressive therapies without the occurrence of HBV reactivation. The serum HBV-DNA levels were prospectively monitored every month, and the incidences of HBV reactivation, defined as a serum HBV-DNA level of 1.3 log IU/ml or more, were evaluated. RESULTS: In the retrospective study, persistent HBV infection was found in 90 patients, and HBV reactivation was responsible for liver injuries in 50 patients including 23 receiving immunosuppressive therapies (26 with HBs-antigen positivity, 7 with prHBV infection). None of seven patients with prHBV infection were rescued. In the prospective studies, HBV reactivation occurred in ten patients, but preemptive entecavir administration prevented liver injury. The cumulative reactivation rate was 3.2 % at 6 months, and the increase of the rate compared to that at 6 months was +1.5 % at 48 months. CONCLUSIONS: HBV reactivation during immunosuppression was responsible for liver injuries in a quarter of the ALF/LOHF patients with persistent HBV infection. Early serum HBV-DNA monitoring may improve patient prognosis, since HBV reactivation typically occurs within 6 months of the start of immunosuppressive therapies in patients with prHBV infection.
BACKGROUND: The significance of HBV reactivation during immunosuppressive therapy was evaluated in three nationwide cohorts including patients with previously resolved HBV (prHBV) infection. METHODS: The clinical features of 1061 patients with acute liver failure (ALF) or late-onset hepatic failure (LOHF) were retrospectively examined, focusing on those who experienced HBV reactivation. Additionally, 420 patients with prHBV infection were prospectively enrolled: 203 received immunosuppressive therapies immediately after enrollment, while the remaining 217 were enrolled after having received immunosuppressive therapies without the occurrence of HBV reactivation. The serum HBV-DNA levels were prospectively monitored every month, and the incidences of HBV reactivation, defined as a serum HBV-DNA level of 1.3 log IU/ml or more, were evaluated. RESULTS: In the retrospective study, persistent HBV infection was found in 90 patients, and HBV reactivation was responsible for liver injuries in 50 patients including 23 receiving immunosuppressive therapies (26 with HBs-antigen positivity, 7 with prHBV infection). None of seven patients with prHBV infection were rescued. In the prospective studies, HBV reactivation occurred in ten patients, but preemptive entecavir administration prevented liver injury. The cumulative reactivation rate was 3.2 % at 6 months, and the increase of the rate compared to that at 6 months was +1.5 % at 48 months. CONCLUSIONS: HBV reactivation during immunosuppression was responsible for liver injuries in a quarter of the ALF/LOHF patients with persistent HBV infection. Early serum HBV-DNA monitoring may improve patient prognosis, since HBV reactivation typically occurs within 6 months of the start of immunosuppressive therapies in patients with prHBV infection.
Entities:
Keywords:
Acute liver failure; De novo hepatitis B; HBV reactivation; Immunosuppressive therapy
Authors: Sung Soo Ahn; Seung Min Jung; Jason Jungsik Song; Yong Beom Park; Jun Yong Park; Sang Won Lee Journal: Yonsei Med J Date: 2018-05 Impact factor: 2.759