Transfusion transmission of hepatitis B virus: still learning more about it

Background  Despite continuous technical improvement in blood donation testing, hepatitis B infection remains a major risk of transfusion‐transmitted viral infection. The residual risk of hepatitis B virus (HBV) transmission is related to the pre‐seroconversion window period (WP), infection with immunovariant viruses, and with occult carriage of HBV infection (OBI). Results and discussion  Reduction of HBV residual risk is achieved by developing more sensitive HBsAg test, by adopting anti‐HBc screening when appropriate, and recently by implementing HBV nucleic acid testing (NAT), either in minipools or more efficiently in individual donations. Compared with serological testing, HBV NAT combines the ability to significantly reduce the window period and to detect OBIs. Clinical observations suggest lower transmission rate of occult HBV than WP. Lower transmission rate might be related to the low viral load generally observed in OBI donors or to the presence of defective variants associated with occult carriage. In addition, there is evidence that OBI‐infected donors carrying neutralizing anti‐HBs (∼50%) are unlikely to be infectious, while those with anti‐HBc only may be more infectious especially in immunocompromised recipients. Immunodeficient elderly and patients receiving immunosuppressive treatments (organ transplantation or cancer chemotherapy) may be susceptible to infection with lower infectious dose even in the presence of anti‐HBs. There is no evidence that blood from anti‐HBc only positive/HBV DNA‐negative donors is infectious. Present evidence suggests that the association of HBsAg and sensitive NAT screening adequately covers risks of HBV transfusion–transmission, allowing to dispense or discontinue anti‐HBc screening, avoiding discarding non‐infectious and precious blood units, particularly in high prevalence areas. Identification of ‘post‐transfusion’ HBV infection relies essentially on clinical evidence of acute infection or on look‐back exercises following the identification of HBV DNA‐positive donations. To protect from HBV infection the increasing number of immunodeficient recipients, maximum sensitivity of HBV NAT is required. As these recipients are also at risk of viral reactivation when previously exposed, anti‐HBc testing and storage of a pre‐transfusion sample when anti‐HBc‐positive would prevent the difficulties of differentiating between transfusion–transmission and reactivation.