Characterization of occult hepatitis B virus from blood donors carrying genotype A2 or genotype D strains

Background/Aims: Nucleic acid testing (NAT) for hepatitis B virus (HBV) DNA in blood donations identified occult HBV infection (OBI) as a potential threat to blood safety. Methods: A collaborative study was undertaken to explore the molecular basis of OBIs prevalent in Europe in relation to clinical and serological data. Results:Ninety-one percent of 77 donor samples of European origin HBV DNA positive but HBV surface antigen (HBsAg) negative were confirmed. Viral load ranged between unquantifiable and 5640 IU/mL (median 25 IU/ml,). Fifty-two strains were genotyped (14 HBVA2 and 38 HBVD)). Compared to HBsAg+ samples, genotype D was significantly more frequent than genotype A2 in OBIs from Poland or Italy (P < 0.04). Amino acid substitutions were concentrated in the immunologically active parts of the Pre-S/S proteins (P < 0.0001) affecting both cellular CD8 T-cell epitopes and B-cell neutralizing Major Hydrophilic Region epitopes. Substitutions were more frequent in OBIs than in HBsAg+ strains of both genotype D (P < 0.001) and A2 (P < 0.01), in OBIs of genotype D than A2 in the 'a' region (P < 0.001) but not cellular epitopes, and in anti-HBs+ than anti-HBs- OBIs (P < 0.001). Conclusions: Results support the hypothesis that humoral and cellular immune pressure on the HBV envelope proteins are major mechanisms generating OBI. (C) 2008 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.