Università degli Studi di Milano, Ospedale San Giuseppe, Division of Hepatology , Milan , Italy.
Expert Opin Biol Ther. 2014 Jul;14(7):1019-31. doi: 10.1517/14712598.2014.912273.
Rituximab (RTX), a chimeric mouse anti-human CD20 monoclonal antibody, is indicated for the treatment of patients with non-Hodgkin's lymphoma, chronic lymphocytic leukemia, granulomatosis with polyangiitis and microscopic polyangiitis, and rheumatoid arthritis, but nowadays it is increasingly used for the treatment of many other immune-mediated disorders. Hepatitis B virus (HBV) reactivation in RTX-treated patients, eventually leading to fatal liver failure, has been reported more often among hepatitis B surface antigen (HBsAg)-positive patients (overt infection) than in HBsAg-negative, antibody to hepatitis B core antigen (anti-HBc) seropositive patients (resolved infection).
This paper reviews the safety of RTX in patients with overt or resolved HBV infection, providing recommendations for its safe use in such patients.
Prior to starting RTX treatment, all patients should be screened for HBV infection. While HBsAg-positive active carriers should receive long-term antiviral treatment with entecavir (ETV) or tenofovir, inactive carriers are candidates for universal prophylaxis with lamivudine, or ETV or tenofovir in selected cases, to prevent hepatitis reactivation. Conversely, for HBsAg-negative anti-HBc positive carriers, that is, those with resolved HBV infection, universal prophylaxis with lamivudine is recommended for those with onco-hematological diseases, whereas watchful monitoring of HBsAg/HBV DNA levels is advisable for all the other indications.
利妥昔单抗(RTX)是一种嵌合鼠抗人 CD20 单克隆抗体,适用于治疗非霍奇金淋巴瘤、慢性淋巴细胞白血病、肉芽肿性多血管炎和显微镜下多血管炎以及类风湿关节炎,但如今它越来越多地用于治疗许多其他免疫介导的疾病。在接受利妥昔单抗治疗的患者中,乙型肝炎病毒(HBV)再激活最终导致致命性肝衰竭的情况,在乙型肝炎表面抗原(HBsAg)阳性患者(显性感染)中比 HBsAg 阴性、乙型肝炎核心抗原抗体(抗-HBc)阳性患者(已解决感染)更为常见。
本文回顾了 RTX 在 HBV 显性或已解决感染患者中的安全性,为其在这些患者中的安全使用提供了建议。
在开始 RTX 治疗之前,所有患者都应进行 HBV 感染筛查。虽然 HBsAg 阳性的活动性携带者应接受恩替卡韦(ETV)或替诺福韦的长期抗病毒治疗,但非活动性携带者是使用拉米夫定、或在某些情况下使用 ETV 或替诺福韦进行普遍预防的候选者,以预防肝炎再激活。相反,对于 HBsAg 阴性抗-HBc 阳性携带者,即已解决 HBV 感染的携带者,对于患有血液肿瘤疾病的患者,建议使用拉米夫定进行普遍预防,而对于所有其他适应证,则建议密切监测 HBsAg/HBV DNA 水平。