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接受抗B细胞治疗患者的乙型肝炎病毒再激活的筛查与管理

Screening for and management of hepatitis B virus reactivation in patients treated with anti-B-cell therapy.

作者信息

Kusumoto Shigeru, Tobinai Kensei

机构信息

Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; and.

Department of Hematology, National Cancer Center Hospital, Tokyo, Japan.

出版信息

Hematology Am Soc Hematol Educ Program. 2014 Dec 5;2014(1):576-83. doi: 10.1182/asheducation-2014.1.576. Epub 2014 Nov 18.

Abstract

Reactivation of hepatitis B virus (HBV) is a potentially fatal complication after anti-B-cell therapy. It can develop not only in patients seropositive for hepatitis B surface antigen (HBsAg), but also in those with resolved HBV infection who are seronegative for HBsAg but seropositive for antibodies against hepatitis B core antigen (anti-HBc) and/or antibodies against HBsAg (anti-HBs). The risk of HBV reactivation depends on the balance between replication of the virus and the immune response of the host. Anti-CD20 monoclonal antibody-rituximab in combination with steroid-containing chemotherapy (R-CHOP: rituximab + cyclophosphamide + hydroxydaunorubicin + vincristine + prednisone/prednisolone)-is an important risk factor for HBV reactivation in HBsAg-negative patients. More obviously, HBsAg-positive patients are considered to be at very high risk for HBV reactivation and, in the rituximab era, 59%-80% of these patients develop HBV reactivation after R-CHOP-like chemotherapy. Patients with resolved HBV infection should also be considered at high risk of HBV reactivation, the incidence of which is reported to be 9%-24% in such lymphoma patients. All patients should be screened to identify risk groups for HBV reactivation before initiating anti-B-cell therapy by measuring serum HBV markers including HBsAg, anti-HBc and anti-HBs. To prevent the development of hepatitis due to HBV reactivation after anti-B-cell therapy, antiviral prophylaxis is recommended for HBsAg-positive patients and/or patients in whom HBV DNA is detectable at baseline, whereas regular monitoring of HBV DNA-guided preemptive antiviral therapy is a reasonable and useful approach for patients with resolved HBV infection.

摘要

乙型肝炎病毒(HBV)再激活是抗B细胞治疗后一种潜在的致命并发症。它不仅可发生于乙型肝炎表面抗原(HBsAg)血清学阳性的患者,也可发生于既往HBV感染已治愈的患者,这些患者HBsAg血清学阴性,但乙型肝炎核心抗原抗体(抗-HBc)和/或乙型肝炎表面抗原抗体(抗-HBs)血清学阳性。HBV再激活的风险取决于病毒复制与宿主免疫反应之间的平衡。抗CD20单克隆抗体利妥昔单抗联合含类固醇化疗(R-CHOP:利妥昔单抗+环磷酰胺+羟基柔红霉素+长春新碱+泼尼松/泼尼松龙)是HBsAg阴性患者发生HBV再激活的一个重要危险因素。更明显的是,HBsAg阳性患者被认为发生HBV再激活的风险非常高,在利妥昔单抗时代,这些患者中有59%-80%在接受类似R-CHOP的化疗后发生HBV再激活。既往HBV感染已治愈的患者也应被视为发生HBV再激活的高危人群,据报道,此类淋巴瘤患者的发生率为9%-24%。在开始抗B细胞治疗前,所有患者均应通过检测血清HBV标志物(包括HBsAg、抗-HBc和抗-HBs)进行筛查,以确定HBV再激活的风险人群。为预防抗B细胞治疗后因HBV再激活导致肝炎的发生,建议对HBsAg阳性患者和/或基线时可检测到HBV DNA的患者进行抗病毒预防,而对于既往HBV感染已治愈的患者,定期监测HBV DNA并根据结果进行抢先抗病毒治疗是一种合理且有用的方法。

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