Purpose of review: The availability of hepatitis B virus (HBV) nucleic acid testing (NAT) for donor blood screening led to its implementation in low prevalence and high prevalence countries. Genomic detection was a substantial addition to HBV surface protein (HBsAg) screening by detecting window period infections and 'occult' HBV infections (OBIs), characterized by undetectable HBsAg, low viral load and presence of serological markers (anti-HBc and/or anti-HBs). OBIs are the result of multiple, poorly understood mechanisms including incomplete immune control mutations of the HBsAg antigenic determinants; abnormal expression of S gene; and inhibition of genome transcription. Infectivity for the recipient is high for window period blood and relatively low for OBIs.
Recent findings: The number of cases identified by NAT ranges between 1 : 1000 and 1 : 50 000, depending on epidemiology and assay sensitivity whether NAT is implemented in individual donations or pools of samples. OBI donors are generally older than 45 years except in Africa, carry very low viral load (median 11-25 IU/ml) and have normal alanine transaminase levels. Cases carrying anti-HBc alone are more infectious than those with low level of anti-HBs. Evidence of HBsAg escape mutants that are undetected by commercial assays has been published. Inhibition of HBsAg mRNA production and export are potential mechanisms of OBI occurrence.
Summary: HBV blood safety is improved by NAT for HBV DNA when applied to individual donations. Until the sensitivity of NAT is improved, both this method and HBsAg screening are needed to eliminate potentially infectious blood donations. Occult HBV characterization clarifies new facets of HBV natural history.