title: Late HBsAg seroreversion of mutated hepatitis B virus after bone marrow transplantation.
abstract: BACKGROUND
  About ninety percent of immunocompetent adults recover from hepatitis B virus (HBV) infection within 6 months after transmission. The infection is considered to be terminated if the antibodies (HBsAb) to the hepatitis B surface antigen (HBsAg) become detectable and the HBsAg and Hepatitis B virus DNA (HBV DNA,) are no longer perceptible. After recovery from an acute infection, the detection of HBsAb is assumed to indicate lifelong immunity. However, after initiation of severe immunosuppression, HBV reactivation, as detected by HBsAg seroreversion may be observed in patients with previously resolved HBV infections.
  
  
  METHODS
  We present an unusual case of a 64-year-old Caucasian woman showing clinically apparent HBV seroreversion more than 45 months after hematopoietic stem cell transplantation (HSCT). Despite living without immunosuppressive agents for more than 40 months, she developed a fulminant HBV infection with detection of a mutated hepatitis B virus carrying two immune escape mutations (D144E/G145R) in the HBsAg (HBsIE mutation).
  
  
  CONCLUSIONS
  After HSCT, the absence of risk factors such as strong immunosuppression and graft-versus-host disease decreases the risk of HBV seroreversion but may rearward seroreversion to a later time. Therefore, when monitoring HSCT, patients with serological markers of a resolved HBV infection [HBcAb + (hepatitis B core antibody), HBsAb+, and HBsAg-], the follow up has to be extended over several years to exclude HBV reactivation with HBsAg seroreversion. Furthermore, this case demonstrates the complexity of virus evolution after HBsAg seroreversion as a result of immunosuppression after HSCT.
authors.forename: Axel
authors.initials: A
authors.lastname: Schubert
authors.forename: Detlef
authors.initials: D
authors.lastname: Michel
authors.forename: Thomas
authors.initials: T
authors.lastname: Mertens
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D016026:Bone Marrow Transplantation / Q000009:adverse effects* / Q000379:methods; D024882:Drug Resistance, Viral; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006509:Hepatitis B / Q000188:drug therapy / Q000209:etiology* / Q000276:immunology / Q000821:virology; D006510:Hepatitis B Antibodies / Q000097:blood; D006512:Hepatitis B Core Antigens / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009154:Mutation; D014775:Virus Activation
chemical_list: D000998:Antiviral Agents; D006510:Hepatitis B Antibodies; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D007166:Immunosuppressive Agents