Occult hepatitis B virus infection of peripheral blood mononuclear cells among treatment-naïve patients with chronic lymphocytic leukemia

Recent guidelines emphasise the risk of hepatitis B virus (HBV) reactivation among patients with hematologic malignancies of B lineage, in which HBV has been recently hypothesised to play a pathogenetic role. We aimed to determine the prevalence of occult HBV infection (OBI) of peripheral blood mononuclear cells, defined as detection of sequences from ≥2 HBV genes in subjects lacking hepatitis B surface antigen, among patients with treatment-naive chronic lymphocytic leukemia (CLL). HBV DNA sequences from four HBV genes (S, X, core and pol) were searched for in archival material obtained at diagnosis (N = 173), and from age and sex-matched controls. OBI was observed in 17/173 (10%) patients and 5/173 (3%) controls (OR = 3.6, 95% CI 1.37-9.79, p = 0.014). OBI was not associated with differences on 5-year survival and biological predictors, but patients with CLL with OBI had significantly lower peripheral blood lymphocyte count. After 8 years of observation without treatment, one OBI positive patient with CLL converted into positive HBsAg serology and developed active hepatitis. In conclusion, OBI is significantly more prevalent among patients with CLL than in age and sex-matched controls, and may contribute to the susceptibility of patients with CLL to HBV reactivation, whether exposed or not to biological agents.