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

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

Valerie Yeap  1 , Wei-Lun Liou  1 , Gayathry Morvil  1 , Rajneesh Kumar  1
Affiliations

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

Valerie Yeap et al. J Clin Exp Hepatol. 2025 Jul-Aug.

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%), P = 0.001. This was confirmed on multivariable analysis (OR 4.19 [C.I. 1.47-11.9], P = 0.007). HBsAb titres of above 100 mIU/ml were protective against HBVr (OR 0.04 [CI 0.001-0.84], P = 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.

Keywords: hepatitis B reactivation; immunosuppression; non-rituximab; resolved hepatitis B infection; rituximab.

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Conflict of interest statement

The authors have no conflicts of interests to disclose.

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