Safety of Immune Checkpoint Inhibitors in Hepatitis B Virus-Positive Cancer Patients: A Multicenter Retrospective Cohort Study

Background: Immune checkpoint inhibitors (ICIs) are widely used in cancer treatment, but their safety in patients with pre-existing hepatitis B virus (HBV) infection remains uncertain. HBV reactivation is a recognized complication of immunosuppressive cancer therapy, yet evidence supporting routine antiviral prophylaxis during ICI treatment is limited. This study evaluated HBV reactivation and HBV-related outcomes among HBV-positive cancer patients receiving ICIs. Methods: This multicenter retrospective cohort study included adult patients treated with ICIs between January 2017 and December 2022. Patients were grouped according to receipt of antiviral prophylaxis. The primary outcome was HBV reactivation during ICI therapy. Secondary outcomes included hepatic flare, severity, and timing of reactivation, response to antiviral therapy, and factors associated with HBV-related outcomes. Results: A total of 160 patients were included; 68 received antiviral prophylaxis and 92 did not. HBV reactivation occurred in 3 patients (1.9%) and the odd ratio between antiviral prophylaxis and HBV reactivation was wide and imprecise (2.76; 95% CI 0.25–31.05). Hepatic flare occurred in 16 patients (10.0%) and was more frequent in the prophylaxis group than in the no-prophylaxis group (19.1% vs. 3.3%; p = 0.001). Conclusion: In this multicenter retrospective cohort study, the HBV reactivation rate was low and could not determine whether antiviral prophylaxis reduced the risk of reactivation. Hepatic flares were significantly more common among patients who received antiviral prophylaxis, likely reflecting a higher baseline risk of HBV-related complications in this group. A future randomized controlled trial is warranted to guide risk-adapted antiviral prophylaxis and monitoring.