title: Nationwide prospective and retrospective surveys for hepatitis B virus reactivation during immunosuppressive therapies.
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.
authors.affiliation: 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.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Mochida
authors.affiliation: Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-cho, Iruma-gun, Saitama, 350-0495, Japan.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Nakao
authors.affiliation: Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-cho, Iruma-gun, Saitama, 350-0495, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Nakayama
authors.affiliation: Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-cho, Iruma-gun, Saitama, 350-0495, Japan.
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Uchida
authors.affiliation: Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-cho, Iruma-gun, Saitama, 350-0495, Japan.
authors.forename: Sumiko
authors.initials: S
authors.lastname: Nagoshi
authors.affiliation: Department of Digestive and Lifestyle Related Diseases, Human and Enviromental Sciences, Health Research, Kagoshima University Graduate School of Medicine and Dental Sciences, Kagoshima, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Ido
authors.affiliation: Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University, Saitama, Japan.
authors.forename: Toshihide
authors.initials: T
authors.lastname: Mimura
authors.affiliation: Department of Pharmacovigilance, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Harigai
authors.affiliation: Division of Rheumatic Diseases, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kaneko
authors.affiliation: Department of Gastroenterology and Rheumatology, School of Medicine, Fukushima Medical University, Fukushima, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kobayashi
authors.affiliation: Department of Dermatology, Saitama Medical University, Saitama, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tsuchida
authors.affiliation: Department of Nephrology, Saitama Medical University, Saitama, Japan.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Department of Nephrology, Teine Keijinkai Hospital, Sapporo, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Ura
authors.affiliation: Department of Hematology, Saitama Medical University, Saitama, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of Hematology, Saitama Medical University, Saitama, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Bessho
authors.affiliation: Department of Hematology, Nippon Medical School, Tokyo, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Dan
authors.affiliation: Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Science, Nagoya, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kusumoto
authors.affiliation: Department of Medical Oncology, International Medical Cnter/Comprehensive Cancer Center, Saitama Medical University, Saitama, Japan.
authors.forename: Yasutsuna
authors.initials: Y
authors.lastname: Sasaki
authors.affiliation: Department of Clinical Oncology, Jichi Medical University, Shimotsuke, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Fujii
authors.affiliation: Department of Hepatology, Toranomon Hospital, Tokyo, Japan.
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Suzuki
authors.affiliation: Department of Hepatology, Toranomon Hospital, Tokyo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Ikeda
authors.affiliation: Department of Allergy and Pheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Department of Medicine, Teikyo University of School of Medicine, Tokyo, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Takikawa
authors.affiliation: Department of Digestive and Lifestyle Related Diseases, Human and Enviromental Sciences, Health Research, Kagoshima University Graduate School of Medicine and Dental Sciences, Kagoshima, Japan.
authors.forename: Hirohito
authors.initials: H
authors.lastname: Tsubouchi
authors.affiliation: The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Mizokami
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000097:blood*; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000502:physiology*; D019694:Hepatitis B, Chronic / Q000150:complications / Q000276:immunology*; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007223:Infant; D007564:Japan; D017114:Liver Failure, Acute / Q000821:virology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012189:Retrospective Studies; D014775:Virus Activation; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D007166:Immunosuppressive Agents
keywords: Acute liver failure; De novo hepatitis B; HBV reactivation; Immunosuppressive therapy
references.citation: Hepatol Res. 2014 Apr;44(4):365-7
references.pmid: 24528608
references.citation: Hepatol Res. 2013 Feb;43(2):97-105
references.pmid: 23409848
references.citation: Gastroenterology. 1991 Jan;100(1):182-8
references.pmid: 1983820
references.citation: Mod Rheumatol. 2011 Feb;21(1):16-23
references.pmid: 20668905
references.citation: Mod Rheumatol. 2011 Dec;21(6):621-7
references.pmid: 21528424
references.citation: Clin Infect Dis. 2015 Sep 1;61(5):719-29
references.pmid: 25935551
references.citation: Intervirology. 2004;47(1):32-40
references.pmid: 15044834
references.citation: J Gastroenterol. 2012 Aug;47(8):849-61
references.pmid: 22825549
references.citation: Int J Hematol. 2009 Jul;90(1):13-23
references.pmid: 19544079
references.citation: Hepatol Res. 2008 Jul;38(7):646-57
references.pmid: 18328067
references.citation: Hepatol Res. 2014 Jan;44 Suppl S1:1-58
references.pmid: 24397839
references.citation: J Gastroenterol. 2011 Apr;46(4):556-64
references.pmid: 21246383
references.citation: Hepatol Res. 2011 Sep;41(9):805-12
references.pmid: 21884340
references.citation: Gastroenterology. 2015 Jan;148(1):215-9; quiz e16-7
references.pmid: 25447850
references.citation: J Clin Microbiol. 2007 Mar;45(3):828-34
references.pmid: 17229858
references.citation: Hepatology. 2009 Sep;50(3):661-2
references.pmid: 19714720
references.citation: J Hepatol. 2012 Aug;57(2):399-420
references.pmid: 22633836
references.citation: Liver Transpl. 2006 Jan;12 (1):124-33
references.pmid: 16382463
references.citation: J Viral Hepat. 2007 Jul;14(7):478-83
references.pmid: 17576389
references.citation: J Hepatol. 2006 Oct;45(4):529-38
references.pmid: 16879891
references.citation: Gastroenterology. 1975 Jan;68(1):105-12
references.pmid: 1054319
references.citation: Hepatol Res. 2012 Jul;42(7):627-36
references.pmid: 22686858
references.citation: N Engl J Med. 2001 Jan 4;344(1):68-9
references.pmid: 11187122
references.citation: Transplantation. 1998 Feb 27;65(4):494-9
references.pmid: 9500622
references.citation: Int J Mol Sci. 2014 Nov 21;15(11):21455-67
references.pmid: 25421241
references.citation: Hepatology. 2015 Jul;62(1):40-6
references.pmid: 25613809