Louhab Imane, Daoudi Hajar, Elcadi Mina, El Amin Ghizlane, Zouaki Amal, Zirar Jalila, Seffar Myriam, Salihoun Mouna, Kabbaj Hakima
Central Laboratory of Hematology, Ibn Sina University Hospital, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, MAR.
Department of Pharmacy, Ibn Sina University Hospital, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, MAR.
Cureus. 2024 Nov 12;16(11):e73550. doi: 10.7759/cureus.73550. eCollection 2024 Nov.
Introduction Anti-tumor necrosis factor alpha (TNFα) therapies have revolutionized the management of Crohn's disease (CD). However, they increase the risk of viral reactivation, particularly hepatitis B virus (HBV). This study aims to define the HBV serological profiles of patients with CD who are candidates for biological therapy, identifying profiles at potential risk for reactivation or exacerbation following immunosuppressive treatment. Materials and methods This descriptive retrospective study included patients with CD, aged over 16 years, who were candidates for anti-TNFα treatment at Ibn Sina University Hospital Center (UHC) in Rabat, Morocco, from January 2015 to March 2023. The serological profiles of patients, including hepatitis B surface antigen (HBsAg), hepatitis B surface antibodies, and total hepatitis B core antibodies (HBcAb), were determined using microparticle chemiluminescence immunoassay with the ARCHITECT i2000sr or Alinity (Abbott Diagnostics, Chicago, Illinois, United States) automated systems at the Central Virology Laboratory (CVL) of Ibn Sina UHC Rabat. HBV DNA quantification was performed using the m2000 Abbott Diagnostic or GeneXpert system. Results Out of 249 patients with CD who were candidates for biological therapy, 131 (52.6%) received anti-TNFα treatment, including 39 (29.8%) with adalimumab and 92 (70.2%) with infliximab. The median age was 41 years, and the male-to-female ratio was 0.52. The overall HBV screening rate before starting biological therapy was 68.7%. HBV screening was conducted for 90 patients at the CVL, where serological marker analysis categorized five distinct profiles. A majority of patients (65, 72.2%) had negative serological profiles for HBV, while 10 (11.1%) were immunized via vaccination. Profiles at risk of viral reactivation or worsening following immunosuppressive therapy included 12 (13.3%) patients immunized by contact, two (2.3%) with isolated HBcAb, and one (1.1%) with active viral hepatitis (positive HBsAg and HBcAb), who was initiated on tenofovir 300 mg before starting combination therapy. No cases of primary infection or viral B reactivation were observed during the study. Conclusions In our study, 15 patients (16.7%) exhibited a potential risk of viral reactivation or worsening of HBV following the initiation of immunosuppressive therapy. The authors recommend precise patient selection, thorough pretreatment evaluation, and regular follow-up during therapy to minimize adverse events associated with anti-TNFα treatment. Additionally, a prophylactic or preemptive strategy should be considered. The risk of late reactivation after discontinuation of biological therapy should also be carefully monitored.
引言 抗肿瘤坏死因子α(TNFα)疗法彻底改变了克罗恩病(CD)的治疗方式。然而,它们会增加病毒再激活的风险,尤其是乙型肝炎病毒(HBV)。本研究旨在确定适合生物治疗的CD患者的HBV血清学特征,识别免疫抑制治疗后有再激活或病情加重潜在风险的特征。
材料与方法 这项描述性回顾性研究纳入了2015年1月至2023年3月在摩洛哥拉巴特伊本·西那大学医院中心(UHC)年龄超过16岁、适合抗TNFα治疗的CD患者。在拉巴特伊本·西那UHC的中央病毒学实验室(CVL),使用ARCHITECT i2000sr或Alinity(美国伊利诺伊州芝加哥雅培诊断公司)自动化系统通过微粒化学发光免疫分析法测定患者的血清学特征,包括乙型肝炎表面抗原(HBsAg)、乙型肝炎表面抗体和乙型肝炎核心抗体总抗体(HBcAb)。使用m2000雅培诊断系统或GeneXpert系统进行HBV DNA定量分析。
结果 在249名适合生物治疗的CD患者中,131名(52.6%)接受了抗TNFα治疗,其中39名(29.8%)使用阿达木单抗,92名(70.2%)使用英夫利昔单抗。中位年龄为41岁,男女比例为0.52。开始生物治疗前的总体HBV筛查率为68.7%。在CVL对90名患者进行了HBV筛查,血清学标志物分析将其分为五种不同特征。大多数患者(65名,72.2%)HBV血清学特征为阴性,而10名(11.1%)通过接种疫苗获得免疫。免疫抑制治疗后有病毒再激活或病情恶化风险的特征包括12名(13.3%)通过接触获得免疫的患者、2名(2.3%)仅有HBcAb的患者以及1名(1.1%)患有活动性病毒性肝炎(HBsAg和HBcAb阳性)的患者,该患者在开始联合治疗前开始服用300毫克替诺福韦。研究期间未观察到原发性感染或乙型病毒再激活病例。
结论 在我们的研究中,15名患者(16.7%)在开始免疫抑制治疗后表现出HBV病毒再激活或病情恶化的潜在风险。作者建议进行精确的患者选择、全面的治疗前评估以及治疗期间的定期随访,以尽量减少与抗TNFα治疗相关的不良事件。此外,应考虑采取预防或先发制人的策略。还应仔细监测生物治疗停药后迟发性再激活的风险。