Hepatitis B Virus Reactivation During Rituximab Therapy Despite Anti-HBs Positivity: A Case Report

Hepatitis B virus (HBV) reactivation is a well-recognized complication of immunosuppressive therapy, particularly with B-cell-depleting agents such as rituximab. Anti-HBs positivity may reflect previous immune control, but it does not eliminate the risk of reactivation in patients with previously resolved HBV infection. We report the case of a 63-year-old man with splenic marginal zone lymphoma treated with rituximab-based chemotherapy. Before treatment, HBV testing showed negative HBsAg, positive anti-HBc, positive anti-HBs, and undetectable HBV DNA. No antiviral prophylaxis was initiated before chemotherapy, although the patient was retrospectively considered at high risk for HBV reactivation because of anti-HBc positivity and planned rituximab therapy. Approximately two months after the last chemotherapy cycle, he developed marked hepatic cytolysis. Further evaluation showed new HBsAg positivity, persistent anti-HBs positivity, and detectable HBV DNA, confirming HBV reactivation with HBsAg seroreversion. Tenofovir disoproxil fumarate was started, resulting in normalization of liver enzymes and sustained virological suppression. This case emphasizes that anti-HBs positivity should not be considered sufficient protection against HBV reactivation in patients receiving rituximab. Systematic HBV screening, guideline-based antiviral prophylaxis in high-risk patients, and prolonged virological monitoring are essential to prevent severe hepatic complications.