Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Pokfulam, Hongkong.
State Key Laboratory of Liver Research, The University of Hong Kong, Pokfulam, Hongkong.
Virol J. 2023 Aug 1;20(1):168. doi: 10.1186/s12985-023-02140-w.
Ibrutinib is a Bruton's tyrosine kinase (BTK) inhibitor approved for the treatment for several mature B-cell malignancies. Reactivation of hepatitis B virus (HBV) is a well-described complication in patients with chronic HBV infection or prior HBV exposure undergoing cytotoxic or immunosuppressive chemotherapy for hematologic malignancies. This phenomenon has been frequently reported with rituximab. However, published data on the risk of HBV reactivation induced by ibrutinib are scarce. Cases of HBV reactivation in hematologic patients receiving ibrutinib therapy have recently been described, but limited only to overt hepatitis B patients or seropositive occult hepatitis B patients.
We report the first case of HBV reactivation during ibrutinib treatment in an asymptomatic 82-year-old woman with seronegative occult hepatitis B patient (i.e., negative for HBsAg, anti-HBc and anti-HBs). Four months after ibrutinib treatment, her liver function test (LFT) was deranged, with seroconversion to HBsAg positivity. Serum hepatitis B virus DNA was quantified to be 1.92 × 10 IU/ml. Antiviral treatment was initiated, and viral load was gradually suppressed with improvement in LFT.
Our case illustrated that in populations with a high incidence of HBV exposure, systematic screening for HBV exposure is essential prior to ibrutinib treatment, followed by serial monitoring of serologic and molecular markers of hepatitis B. There is a need for an international consensus to support the recommendation of antiviral prophylaxis against HBV reactivation in patients using ibrutinib.
伊布替尼是一种布鲁顿酪氨酸激酶（BTK）抑制剂，已被批准用于治疗多种成熟 B 细胞恶性肿瘤。在患有慢性乙型肝炎病毒（HBV）感染或既往 HBV 暴露的患者中，细胞毒性或免疫抑制化疗会导致 HBV 再激活，这是一种已知的并发症。这种现象在利妥昔单抗中经常被报道。然而，关于伊布替尼引起的 HBV 再激活风险的已发表数据很少。最近有报道称，接受伊布替尼治疗的血液系统恶性肿瘤患者出现 HBV 再激活，但仅限于显性乙型肝炎患者或血清阳性隐匿性乙型肝炎患者。
我们报告了首例接受伊布替尼治疗的无症状 82 岁女性隐匿性乙型肝炎患者（即 HBsAg、抗 HBc 和抗 HBs 均为阴性）发生 HBV 再激活的病例。伊布替尼治疗 4 个月后，其肝功能检查（LFT）异常，出现 HBsAg 阳性血清转换。乙型肝炎病毒 DNA 血清定量为 1.92×10 IU/ml。开始进行抗病毒治疗，随着 LFT 的改善，病毒载量逐渐得到抑制。
我们的病例表明，在 HBV 暴露发生率较高的人群中，在开始伊布替尼治疗之前，必须对 HBV 暴露进行系统筛查，随后对乙型肝炎的血清学和分子标志物进行连续监测。需要制定国际共识，以支持推荐使用伊布替尼的患者进行 HBV 再激活的抗病毒预防。
