Hepatitis B Screening, Antiviral Prophylaxis, and Reactivation Risk in Rituximab-Treated Patients: A 17-Year Population-Based Cohort Study Highlighting Current Practices and Gaps.

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.