title: Hepatitis B virus reactivation by immunosuppressive therapy in patients with autoimmune diseases: risk analysis in Hepatitis B surface antigen-negative cases.
abstract: OBJECTIVE
  To evaluate the risk of reactivation of resolved hepatitis B virus (HBV) by immunosuppressive therapy in patients with autoimmune diseases.
  
  
  METHODS
  Thirty-five patients with autoimmune diseases were included in our study; all were hepatitis B surface antigen (HBsAg)-negative and antibody against hepatitis B core antigen-positive. They were followed for 8-124 weeks and clinical outcomes were analyzed, including serum levels of HBV-DNA and aminotransferase every 4 weeks during their immunosuppressive therapy for underlying autoimmune diseases. If HBV-DNA was detected during the immunosuppressive therapy, HBsAg, antibody against HBsAg (anti-HBs), hepatitis B e antigen (HBeAg), and antibody against HBeAg were also monitored every 4 weeks.
  
  
  RESULTS
  HBV-DNA was detected in 6 out of 35 patients. Anti-HBs titer was significantly lower in the patients in whom HBV-DNA was detected compared with the others at baseline: 2.83 (range 0.24-168.50) mIU/ml vs 99.94 (range 0.00-5342.98) mIU/ml, respectively (p = 0.036). Outcomes of the 6 patients with HBV reactivation were as follows: HBV-DNA turned negative in 2 patients without nucleic acid analog (NAA) and 1 with NAA; 2 died due to bacterial sepsis; and 1 died due to autoimmune hemolytic anemia. Significant elevation of aminotransferase was found in only 1 patient, but HBsAg converted to positive in 2 patients and HBeAg converted to positive in 1 patient.
  
  
  CONCLUSIONS
  Reactivation of resolved HBV can occur during standard immunosuppressive therapy for autoimmune diseases. The low titer of baseline anti-HBs may carry its risk.
authors.affiliation: Department of Medicine II, Hokkaido University Graduate School of Medicine, N15W7 Kita-Ku, Sapporo 060-8638, Japan. ktmasaru@med.hokudai.ac.jp
authors.forename: Masaru
authors.initials: M
authors.lastname: Kato
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Atsumi
authors.forename: Takashi
authors.initials: T
authors.lastname: Kurita
authors.forename: Toshio
authors.initials: T
authors.lastname: Odani
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Fujieda
authors.forename: Kotaro
authors.initials: K
authors.lastname: Otomo
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Horita
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Yasuda
authors.forename: Takao
authors.initials: T
authors.lastname: Koike
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001327:Autoimmune Diseases / Q000188:drug therapy*; D004279:DNA, Viral / Q000276:immunology; D005260:Female; D006512:Hepatitis B Core Antigens / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000502:physiology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D018570:Risk Assessment; D014775:Virus Activation / Q000187:drug effects* / Q000276:immunology
chemical_list: D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D007166:Immunosuppressive Agents