A Sleeping Giant: Late HBV Reactivation After Rituximab-Based Chemotherapy Despite Correct Prophylaxis

Hepatitis B virus (HBV) reactivation is a recognized complication of long-term immunosuppressive or cytotoxic therapy, typically occurring during immunosuppression or within a few months after treatment. To mitigate this risk, hepatological societies recommend the use of nucleos(t)ide analogues (NA) for HBV reactivation prophylaxis, along with post-treatment monitoring; though, these recommendations are not universally consistent across different guidelines. We present a case of late HBV reactivation in a 76-year-old male with occult HBV infection who received rituximab-based therapy for chronic lymphocytic leukemia. In accordance with HBV reactivation guidelines, the patient was prescribed entecavir 0.5 mg daily during chemotherapy and for 18 months following the completion of hematological treatment. Despite adherence to these recommendations, the patient developed HBV reactivation 2 years and 5 months after the cessation of rituximab-based therapy, which progressed to acute HBV hepatitis. Our case emphasizes the need for extended follow-up in patients undergoing rituximab-based immunosuppression. It highlights the critical importance of vigilance for HBV reactivation and the potential consequences of delayed treatment. This case supports evidence on the unpredictability of HBV reactivation timelines and underscores the need for standardized monitoring protocols.