Background: Hepatitis B virus (HBV) infection is a common comorbidity in patients with B-cell lymphoma (BCL), yet its impact on long-term outcomes remains inadequately explored. This study aims to investigate the association between HBV infection and survival outcomes in BCL patients, with particular focus on the potential synergistic effect of hemophagocytic syndrome (HPS).

Methods: We conducted a retrospective cohort study of 389 consecutive BCL patients diagnosed by pathological biopsy at Huadong Hospital, Fudan University (January 2013–December 2021). Patients were stratified based on hepatitis B surface antigen (HBsAg) status (positive [n=191, 49.1%] vs. negative [n=198, 50.9%]). The primary endpoints were overall survival (OS) and progression-free survival (PFS), analyzed using Kaplan-Meier curves with log-rank tests. Multivariable Cox regression and propensity score matching (PSM) were applied to adjust for confounders. Subgroup analyses examined interaction effects, particularly in patients with concurrent HPS.

Results: HBsAg-positive patients showed significantly inferior OS (HR 1.77, 95% CI 1.16–2.70; p=0.007) and PFS (HR 1.35, 95% CI 1.07–1.72; p=0.014) compared to HBsAg-negative patients. These results remained consistent after multivariable adjustment (adjusted p<0.05 for both OS/PFS) and PSM. The prognostic impact of HBV infection was notably exacerbated in patients with concurrent HPS (OS interaction p=0.001; PFS interaction p=0.003), indicating a synergistic detrimental effect.

Conclusion: HBV infection is an independent predictor of poor long-term outcomes in BCL patients, with an increased risk in those who develop HPS. These findings highlight the importance of integrated HBV monitoring and targeted interventions in this high-risk cohort.

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