Klutsch Solenn, Boschi Céline, Motte Anne, Halfon Philippe, Borentain Patrick, Gerolami René, Colson Philippe
Assistance Publique-Hôpitaux de Marseille, (AP-HM), Centre Hospitalo-Universitaire Timone, service d'Hépatologie, Marseille, France.
IHU Méditerranée Infection, Marseille, France.
J Med Virol. 2025 Jul;97(7):e70480. doi: 10.1002/jmv.70480.
Reactivations of hepatitis B virus (HBV) infection in severely immunocompromised patients with serological profiles of past hepatitis B are non-exceptional and potentially severe or fatal events. The preventive and pre-emptive detection of this serological status is compromised in the absence of antibodies to hepatitis B core antigen (anti-HBc), 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-HBc, suggesting the absence of detectable anti-HBc in this patient at the stage of past infection. Next-generation 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-HBc. Nonetheless, W28* pre-core 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-HBc 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-HBc.
在既往有乙肝血清学特征的严重免疫功能低下患者中，乙肝病毒（HBV）感染再激活并非罕见，且可能是严重或致命事件。在极少数HBV感染病例中，由于缺乏乙肝核心抗原抗体（抗-HBc），这种血清学状态的预防性和抢先检测受到影响。在此，我们描述了一例患者，其血清学特征显示曾接种过HBV疫苗，但该患者并未报告既往接种史，该患者在接受包括利妥昔单抗在内的淋巴瘤化疗后出现了HBV再激活。该患者出现了乙肝表面抗原（HBsAg）但未出现抗-HBc，提示在既往感染阶段该患者未检测到可检测的抗-HBc。二代测序提供了完整的HBV基因组，显示HBsAg存在与免疫逃逸相关的突变，但未检测到先前描述的与抗-HBc缺失显著相关的核心基因突变。尽管如此，发现了W28*前核心突变，据报道在免疫反应较弱的情况下该突变会增强复制能力，并怀疑与免疫逃逸突变一起促进HBV再激活。总体而言，该病例突出表明，抗-HBc阴性不能绝对排除既往HBV感染以及血液系统疾病治疗背景下免疫功能低下患者HBV再激活的风险，并且对于既往有HBV感染但未检测到抗-HBc的患者，很难评估这种风险以及预防或监测HBV再激活。
