Background: Hepatitis B virus (HBV) reactivation is a potentially severe and preventable complication of immunosuppressive therapy, particularly with anti-CD20 agents such as rituximab, underscoring the need for effective screening and prophylaxis to reduce adverse outcomes.
Methods: We conducted a retrospective population-based cohort study using the Clalit Health Services database in northern Israel. Adult patients aged ≥ 18 years who received rituximab between 2005 and 2022 were included. HBV screening (HBsAg and anti-HBc), antiviral prophylaxis, and HBV reactivation events were evaluated. Timely screening was defined as testing performed within 90 days before rituximab initiation. Temporal trends were analyzed using the Cochran-Armitage test, and predictors of reactivation were evaluated using Cox proportional hazards models, with the per-patient analysis considered the primary model.
Results: After exclusion of patients younger than 18 years, a total of 11,888 adult patients received rituximab during the study period (mean age 61.6 ± 15.6 years; 54.7% female). Only 10.5% of patients underwent timely HBV screening before treatment initiation, while 47.4% were never screened without time restriction and 89.5% had no HBV serology within 90 days before rituximab initiation. Among screened patients, approximately 6.0% had evidence of current or prior HBV infection. Screening rates improved significantly over time (P < 0.0001) but remained suboptimal across clinical settings. Antiviral prophylaxis increased over the study period but plateaued at approximately 50% among eligible patients. A total of 159 HBV reactivation events were identified, corresponding to an incidence of 1.06% per treatment event and approximately 1.3% per patient. Reactivation occurred predominantly among patients who had not undergone HBV screening. Multivariable analysis identified male sex as an independent predictor of HBV reactivation.
Conclusions: Despite gradual improvement over nearly two decades, HBV screening before rituximab therapy remains insufficient in real-world clinical practice. Given that HBV reactivation is largely preventable with appropriate screening and antiviral prophylaxis, system-level interventions are needed to improve adherence to guideline-recommended care.
Keywords: Antiviral prophylaxis; HBV reactivation; Hepatitis B screening; Immunosuppressive therapy; Rituximab.
© 2026. The Author(s).