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J Hepatol. 2008 Oct;49(4):537-47. doi: 10.1016/j.jhep.2008.04.017. Epub 2008 Jun 2.

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

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  • 1National Health Service Blood and Transplant, Cambridge Blood Centre, Cambridge, UK.



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.


A collaborative study was undertaken to explore the molecular basis of OBIs prevalent in Europe in relation to clinical and serological data.


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 HBV(A2) and 38 HBV(D)). 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).


Results support the hypothesis that humoral and cellular immune pressure on the HBV envelope proteins are major mechanisms generating OBI.

[PubMed - indexed for MEDLINE]
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