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利妥昔单抗化疗期间乙肝表面抗体(抗-HBs)动力学及免疫抑制前乙肝疫苗接种效果:两项前瞻性研究

Hepatitis B Surface Antibody (Anti-HBs) Kinetics during Rituximab Chemotherapy and Performance of Hepatitis B Vaccine before Immunosuppression: Two Prospective Studies.

作者信息

Araujo-Neto João Marcello de, Guimarães Gabriela Sousa, Fernandes Flavia Ferreira, Soares Marcelo A

机构信息

Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil.

Instituto Nacional do Câncer Jose Alencar Gomes da Silva, Rio de Janeiro 20230-130, Brazil.

出版信息

Viruses. 2022 Aug 15;14(8):1780. doi: 10.3390/v14081780.

Abstract

Rituximab promotes strong immunosuppression leading to a high risk of hepatitis B reactivation (HBV-R) and chronic infection. Current recommendations on HBV-R prevention are expensive and poorly individualized. In resolved hepatitis B patients, previous studies suggest that anti-HBs titers before immunosuppression can predict HBV-R risk. However, guidelines claim that additional data are necessary before recommending spare drug prophylaxis in patients with high anti-HBs titers. On the other hand, in patients with no previous contact with HBV, guidelines recommend vaccine before immunosuppression despite minimal evidence available. To shed light on these knowledge gaps, two prospective studies were conducted to evaluate anti-HBs in hematological cancer patients treated with rituximab. In the first study, anti-HBs-positive patients were referred for following up antibody titers before and during immunosuppression. Patients with anti-HBs ≥ 100 mIU/mL before immunosuppression had no negative seroconversion (anti-HBs loss), in contrast to 18% of those with anti-HBs < 100 mIU/mL. In the second study, patients with no previous contact with HBV were invited to receive HBV vaccine before rituximab chemotherapy. None seroconverted with anti-HBs. In conclusion, both studies reinforce the need to review concepts about HBV prevention during immunosuppression on current guidelines. Narrowing the use of drug prophylaxis and improving vaccine indications are recommended.

摘要

利妥昔单抗会导致强烈的免疫抑制,从而引发乙肝病毒再激活(HBV-R)和慢性感染的高风险。目前关于HBV-R预防的建议费用高昂且个体化程度低。在乙肝已康复的患者中,先前的研究表明免疫抑制前的抗-HBs滴度可预测HBV-R风险。然而,指南称在推荐对高抗-HBs滴度患者进行备用药物预防之前,还需要更多数据。另一方面,对于既往未接触过HBV的患者,尽管现有证据极少,指南仍建议在免疫抑制前接种疫苗。为了填补这些知识空白,开展了两项前瞻性研究来评估接受利妥昔单抗治疗的血液系统癌症患者的抗-HBs情况。在第一项研究中,抗-HBs阳性患者被转诊以在免疫抑制前后监测抗体滴度。免疫抑制前抗-HBs≥100 mIU/mL的患者未出现血清学阴性转换(抗-HBs消失),而抗-HBs<100 mIU/mL的患者中有18%出现了血清学阴性转换。在第二项研究中,既往未接触过HBV的患者被邀请在接受利妥昔单抗化疗前接种乙肝疫苗。无人产生抗-HBs血清学转换。总之,两项研究均强化了根据当前指南重新审视免疫抑制期间乙肝预防概念的必要性。建议缩小药物预防的使用范围并改进疫苗接种指征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/daa8/9415137/b76fbcb55fd2/viruses-14-01780-g001.jpg

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