Both chronic HBV infection and naturally acquired HBV immunity confer increased risks of B-cell non-Hodgkin lymphoma

BACKGROUND: Previous studies examining the relationship between hepatitis B virus (HBV) infection and non-Hodgkin lymphoma (NHL) show inconsistent results in different endemic areas. Furthermore, studies evaluating the association between stratified HBV status and NHL with a well-matched case-control design are rare. METHODS: We conducted a 1:2 case-control study enrolling 3502 NHL cases and 7004 controls, and performed an updated meta-analysis evaluating the association between HBV and NHL subtypes. RESULTS: The HBsAg-negative/anti-HBc-positive/anti-HBs-positive population, implying naturally acquired immunity after infection, had increased B-NHL risk (Adjusted odds ratio (AOR) (95% confidence interval (95% CI)): 2.25 (1.96-2.57)). The HBsAg-positive/HBeAg-positive population, indicating current HBV infection, had high risk of B-NHL (AOR (95% CI): 6.23 (3.95-9.82)). Specifically, for diffuse large B-cell lymphoma (DLBCL), there was no significant difference in HBsAg status between the germinal centre B (GCB) and non-GCB subtypes. Additionally, our meta-analysis showed in a random effects model, HBV-infected individuals had a pooled OR of 2.09 (95% CI 1.76-2.50; P < 0.01) for NHL. CONCLUSIONS: Chronic HBV infection was positively associated with B-NHL in China. However, acquired immunity by natural infection also increased B-NHL risk. Thus, we further speculated that regardless of whether HBsAg was cleared, the infected population had higher risk of B-NHL. Our study might expand our knowledge on tumorogenesis of NHL and thus provides clues for novel treatment strategies.