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The preventive and pre\u2010emptive detection of this serological status is compromised in the absence of antibodies to hepatitis B core antigen (anti\u2010HBc), observed in a very small number of cases of HBV infection. Here, we describe the case of a patient with a serological profile indicating a HBV vaccination although the patient did not report previous vaccination, following lymphoma and chemotherapy including rituximab. This patient presented HBV reactivation with appearance of hepatitis B surface antigen (HBsAg) but without appearance of anti\u2010HBc, suggesting the absence of detectable anti\u2010HBc in this patient at the stage of past infection. Next\u2010generation sequencing provided the complete HBV genome, showing the presence of a mutation in HBsAg associated with immune escape but without the detection of mutations in the core gene previously described as significantly associated with the absence of anti\u2010HBc. Nonetheless, W28* pre\u2010core mutation was found, which was reported to enhance replication capacity in case of weak immune responses and suspected to promote HBV reactivation in association with immune escape mutations. Overall, this case highlights that negativity of anti\u2010HBc cannot definitely rule out past HBV infection and the risk of HBV reactivation in immunocompromised patients in the context of treatment of hemopathies, and that it is difficult to assess such a risk and to prevent or monitor HBV reactivation in patients with past HBV infection but no detectable anti\u2010HBc.<\/jats:p>","DOI":"10.1002\/jmv.70480","type":"journal-article","created":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T14:56:00Z","timestamp":1752072960000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Fatal Hepatitis B Reactivation in Absence of Antibody to Hepatitis B Core Antigen in a Lymphoma Patient"],"prefix":"10.1002","volume":"97","author":[{"given":"Solenn","family":"Klutsch","sequence":"first","affiliation":[{"name":"Assistance Publique\u2010H\u00f4pitaux de Marseille (AP\u2010HM), Centre Hospitalo\u2010Universitaire Timone, 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