有乙型肝炎病毒（HBV）感染史的患者在接受化療或者免疫抑制劑治療后，可能HBV會復(fù)活。而HBV的再次激將會引起嚴(yán)重后果甚至可能致命。不過這可能只是冰山一角。這篇review文章發(fā)表在近期的Hepatology雜志上。

    乙型肝炎由體液接觸傳播，導(dǎo)致急性或慢性肝炎。接種疫苗有助于控制乙肝病毒的傳播。醫(yī)學(xué)統(tǒng)計(jì)估計(jì)，全球人口有10%感染有慢性HBV.

    美國食品和藥物管理局（FDA）曾于2013年9月簽署了一份藥物安全溝通書，表示警告免疫抑制和抗癌藥物奧法木單抗（Arzerra ofatumumab）和利妥昔單抗（Rituxan）引起的HBV再激活。奧法木單抗和利妥昔單抗是單克隆抗體治療的藥物，從免疫系統(tǒng)B細(xì)胞中找到，靶向蛋白CD20.這些抗CD20的藥物被用于治療自身免疫性疾病，白血病，淋巴瘤和移植排斥。

    文章主要作者阿德里安博士說道：“雖然FDA要求臨床醫(yī)生開始使用奧法木單抗和利妥昔單抗之前，篩查患者乙肝以防止病毒復(fù)發(fā)，但這可能只是冰山的一角。”

    檢測HBV感染，醫(yī)生會檢測患者的血液，尋找的乙肝表面抗原（HBsAg）。HBsAg抗體在所有HBV患者都存在，甚至在HBsAg清除后，這表示為疾病的再活化的可能。HBV再激活可能引起嚴(yán)重的急性肝功能衰竭，甚至死亡。曾有研究報(bào)告表示HBV再復(fù)活有25%的致死率。

    作者在系統(tǒng)文獻(xiàn)回顧后，總結(jié)了有關(guān)HBV再激活的504例病例。雖然目前還不清楚如何HBV再發(fā)生，專家認(rèn)為，免疫損傷同時(shí)病毒**可能引發(fā)這一進(jìn)程。乙肝病毒的再活化可以與化療，器官和組織移植，高劑量的皮質(zhì)類固醇使用和用于治療風(fēng)濕性疾病靶向腫瘤壞死因子-α（TNF-α）的抗TNF藥物，包括類風(fēng)濕性關(guān)節(jié)炎，消化系統(tǒng)疾病包括克羅恩病和結(jié)腸炎，以及皮膚病，如牛皮癬。

    研究人員總結(jié)表明，HBV激活的問題可能遠(yuǎn)遠(yuǎn)超出了使用兩個(gè)抗CD20藥物引起的情況。進(jìn)一步研究各種醫(yī)學(xué)學(xué)科之間的合作將有助于擴(kuò)大HBV再激活的理解。

    DOI: 10.1002/hep.27609

    Recent US Food and Drug Administration warnings on hepatitis B reactivation with immune-suppressing and anticancer drugs: Just the tip of the iceberg?

    Adrian M. Di Bisceglie, Anna S. Lok, Paul Martin, Norah Terrault, Robert P. Perrillo and Jay H. HoofnagleAbstract

    Reactivation of hepatitis B in the context of immunosuppressive therapy may be severe and potentially fatal. The US Food and Drug Administration has recently drawn attention to the potentially fatal risk of hepatitis B reactivation in patients receiving the anti-CD20 agents ofatumumab or rituximab. This action focuses attention on the broader issue of hepatitis B virus reactivation, which may occur with a wide variety of immunosuppressive therapies in benign or malignant disease. This article summarizes the data behind this issue. These data support the recommendation that all patients undergoing chemotherapy, immunosuppressive therapy, hematopoietic stem cell transplantation, or solid organ transplantation be screened for active or prior hepatitis B viral infection by testing for hepatitis B surface antigen and the antibody to hepatitis B core antigen in serum. Those who are found to be hepatitis B surface antigen–positive should start appropriate antiviral therapy to prevent reactivation. Additionally, even those who have recovered from hepatitis B will benefit from antiviral therapy in certain circumstances because of the risks associated with a form of hepatitis B virus reactivation referred to as “reverse seroconversion.” There remain many uncertain areas that warrant further study, and further advances will benefit from close interactions between various medical specialties, regulatory agencies, and researchers. Conclusions: There is good evidence to support routine screening of all patients for hepatitis B prior to undergoing chemotherapy or immunosuppressive treatment; use of prompt antiviral treatment appears to diminish the risk of severe or fatal reactivation of hepatitis B. （Hepatology 2015;61:703-711）