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靶向治疗时代血液系统恶性肿瘤患者乙型肝炎病毒再激活的预防与管理

英文原题:Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies in the targeted therapy era.

PubMed 2023/09/07(内容时间) World J Gastroenterol Q1 · IF 7.7(JCR 2025)

研究概要

由乙型肝炎病毒(HBV)再激活引起的肝炎可能很严重,甚至可能致命,但是可以预防的。

中文摘要

乙型肝炎病毒(HBV)再激活可导致严重甚至致命的肝炎,但可以预防。HBV再激活最常见于接受化疗的患者,尤其是接受含利妥昔单抗治疗的血液系统恶性肿瘤患者,以及接受干细胞移植者。非活动性甚至既往已清除HBV感染的患者,肝脏内仍可能残留HBV基因组,其表达受免疫系统控制。免疫细胞、尤其是B细胞受到抑制或清除时,表面上已清除的HBV感染可能再激活。因此,所有接受抗癌治疗的血液系统恶性肿瘤患者均应通过血液检测乙型肝炎表面抗原(HBsAg)和乙型肝炎核心抗体,筛查活动性或既往HBV感染。HBsAg阳性患者应接受预防性抗病毒治疗。对于既往感染已清除者,可采用两种策略:一是定期监测HBV DNA,在检出病毒后立即开始抗病毒治疗;二是预防性抗病毒治疗,特别适用于接受高危治疗者,尤其是抗CD20单克隆抗体或造血干细胞移植患者。恩替卡韦和替诺福韦是优选抗病毒药物。过去十年出现了许多治疗血液系统恶性肿瘤的有效新疗法,例如嵌合抗原受体(CAR)T细胞疗法、新型单克隆抗体、双特异性抗体药物偶联物及小分子抑制剂,这些疗法可能与HBV再激活有关。尽管目前证据有限,尚不足以确定最佳预防措施,作者建议HBsAg阳性患者接受新型治疗(包括布鲁顿酪氨酸激酶抑制剂、BCL-2抑制剂及CAR-T疗法)时进行抗病毒预防。仍需进一步研究明确这些药物相关的HBV再激活风险及最佳预防策略。

展开英文摘要原文

Hepatitis due to hepatitis B virus (HBV) reactivation can be serious and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving chemotherapy, especially rituximab-containing therapy for hematological malignancies and those receiving stem cell transplantation. Patients with inactive and even resolved HBV infection still have persistence of HBV genomes in the liver. The expression of these silent genomes is controlled by the immune system. Suppression or ablation of immune cells, most importantly B cells, may lead to reactivation of seemingly resolved HBV infection. Thus, all patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen. Patients found to be positive for HBsAg should be given prophylactic antiviral therapy. For patients with resolved HBV infection, there are two approaches. The first is pre-emptive therapy guided by serial HBV DNA monitoring, and treatment with antiviral therapy as soon as HBV DNA becomes detectable. The second approach is prophylactic antiviral therapy, particularly for patients receiving high-risk therapy, especially anti-CD20 monoclonal antibody or hematopoietic stem cell transplantation. Entecavir and tenofovir are the preferred antiviral choices. Many new effective therapies for hematological malignancies have been introduced in the past decade, for example, chimeric antigen receptor (CAR)-T cell therapy, novel monoclonal antibodies, bispecific antibody drug conjugates, and small molecule inhibitors, which may be associated with HBV reactivation. Although there is limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBsAg-positive patients receiving novel treatments, including Bruton's tyrosine kinase inhibitors, B-cell lymphoma 2 inhibitors, and CAR-T cell therapy. Further studies are needed to determine the risk of HBV reactivation with these agents and the best prophylactic strategy.

论文信息

作者
Mak JWY、Law AWH、Law KWT、Ho R、Cheung CKM、Law MF
第一作者单位
Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong 852, China.United Kingdom
通讯作者单位
Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong 852, China. mflaw99@yahoo.com.hk.United Kingdom
文献类型
综述
期刊
World journal of gastroenterology2023 Sep 7
原文标识
PubMed 37731995 · DOI 10.3748/wjg.v29.i33.4942