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在接受利妥昔单抗和非利妥昔单抗为基础的免疫抑制治疗且未进行化学预防的乙肝已康复患者中,乙肝再激活的真实世界患病率。

Real-world Prevalence of Hepatitis B Reactivation in Patients With Resolved Hepatitis B Receiving Rituximab and Non-rituximab-based Immunosuppressive Therapy Without Chemoprophylaxis.

作者信息

Yeap Valerie, Liou Wei-Lun, Morvil Gayathry, Kumar Rajneesh

机构信息

Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore.

出版信息

J Clin Exp Hepatol. 2025 Jul-Aug;15(4):102551. doi: 10.1016/j.jceh.2025.102551. Epub 2025 Mar 21.

Abstract

BACKGROUND

Hepatitis B virus reactivation (HBVr) can occur in patients with resolved hepatitis B virus (HBV) infection receiving immunosuppressive therapy. The class of immunosuppression influences HBV reactivation (HBVr) risk, with B-cell depleting agents such as Rituximab conferring a higher risk. The presence of hepatitis B surface antibodies (HBsAb) may be protective against HBVr.

OBJECTIVE

To compare the rates of HBVr amongst individuals with resolved HBV infection receiving rituximab and non-rituximab immunosuppressive therapy, without chemoprophylaxis. Our secondary objective was to explore the role of HBsAb in risk stratification for HBVr.

METHODS

We retrospectively collected the data of patients with resolved HBV infection receiving immunosuppressants between 2014 and 2022. HBVr rates amongst patients receiving rituximab and non-rituximab therapy were compared. Logistic regression analysis was performed to identify risk factors for HBVr.

RESULTS

148 patients with resolved HBV infection did not receive chemoprophylaxis. Of the 20 (13.5%) patients who developed HBVr, none developed HBV flare. 42 of the 148 (28.3%) patients received rituximab-based therapy. Patients who received rituximab had a higher risk of HBVr, 12(28.6%) vs 8(7.5%),  = 0.001. This was confirmed on multivariable analysis (OR 4.19 [C.I. 1.47-11.9],  = 0.007). HBsAb titres of above 100 mIU/ml were protective against HBVr (OR 0.04 [CI 0.001-0.84],  = 0.039) in the rituximab exposed cohort, but not in the non-rituximab exposed cohort.

CONCLUSION

The risk of HBVr was higher in patients receiving rituximab; however, no patient developed HBV flare. In patients with resolved HBV infection, the presence of HBsAb titres above 100 mIU/ml may confer additional protection against HBVr and can be used as part of risk stratification for HBVr. In such patients, close surveillance with on-demand therapy instead of chemoprophylaxis may be considered.

摘要

背景

乙肝病毒再激活(HBVr)可发生于接受免疫抑制治疗的乙肝病毒(HBV)感染已缓解患者中。免疫抑制的类型会影响HBV再激活(HBVr)风险,诸如利妥昔单抗等B细胞耗竭剂会带来更高风险。乙肝表面抗体(HBsAb)的存在可能对HBVr具有保护作用。

目的

比较接受利妥昔单抗和非利妥昔单抗免疫抑制治疗且未进行化学预防的HBV感染已缓解个体的HBVr发生率。我们的次要目的是探讨HBsAb在HBVr风险分层中的作用。

方法

我们回顾性收集了2014年至2022年间接受免疫抑制剂治疗的HBV感染已缓解患者的数据。比较了接受利妥昔单抗和非利妥昔单抗治疗患者的HBVr发生率。进行逻辑回归分析以确定HBVr的危险因素。

结果

148例HBV感染已缓解患者未接受化学预防。在发生HBVr的20例(13.5%)患者中,无患者发生乙肝发作。148例患者中有42例(28.3%)接受了基于利妥昔单抗的治疗。接受利妥昔单抗治疗的患者发生HBVr的风险更高,分别为12例(28.6%)和8例(7.5%),P = 0.001。多变量分析证实了这一点(比值比4.19[置信区间1.47 - 11.9],P = 0.007)。在接受利妥昔单抗治疗的队列中,HBsAb滴度高于100 mIU/ml对HBVr具有保护作用(比值比0.04[置信区间0.001 - 0.84],P = 0.039),但在未接受利妥昔单抗治疗的队列中则不然。

结论

接受利妥昔单抗治疗的患者发生HBVr的风险更高;然而,无患者发生乙肝发作。在HBV感染已缓解的患者中,HBsAb滴度高于100 mIU/ml可能对HBVr提供额外保护,并可作为HBVr风险分层的一部分。对于此类患者,可考虑密切监测并根据需要进行治疗而非化学预防。

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