Infectivity of Hepatitis B Virus Surface Antigen‐Positive Plasma With Undetectable HBV‐DNA: Can HBsAg Screening Be Discontinued in Egyptian Blood Donors?

Hepatitis B Virus (HBV) infectivity data were reviewed and the 50% infectious dose (ID₅₀) was reassessed in different HBsAg-positive infection stages enabling modelling of transfusion-transmitted (TT)-HBV infection risk if HBsAg donor screening was replaced by individual donation nucleic acid amplification technology (ID-NAT). Quantitative HBsAg and HBV-DNA assays were performed against international standards to compare the ratio between potential infectious HBV virions and subviral HBsAg particles in Egyptian HBsAg-positive blood donors as well as in Japanese chimpanzee samples of known infectivity. HBV-DNA load below the quantification limit of detection was estimated against a reference standard by replicate NAT testing (n = 25). Infectivity of chimpanzee samples collected during ramp-up and declining viremic phase were tested in a human liver chimeric mice (HLCM) model and compared with published infectivity data from different HBsAg-positive infection stages. Lowest estimates of ID₅₀ in HBsAg-positive plasma were 3-6 HBV virions in chimpanzee studies. Infectivity decreased approximately 10-100-fold in the declining viremic phase using HLCM. In acute phase samples, HBV to HBsAg particle ratios varied between 1:10²-10⁴ but in HBsAg-positive blood donors this particle ratio reached 1:10⁶-10¹² when viral load was below 100 HBV-DNA copies/mL. Modelled TT-HBV risk of an HBsAg-positive/ID-NAT nonreactive blood transfusion was estimated at 5.5%-27% for components containing 20-200 mL of plasma when assuming an ID₅₀ of 316 (point estimate between 100 and 1000) virions. It cannot be ensured that discontinuation of HBsAg donor screening and reliance on ID-NAT alone is safe.