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

• Published in: Journal of hepatology Vol. 49; no. 4; pp. 537 - 547
• Main Authors: Candotti, Daniel, Grabarczyk, Piotr, Ghiazza, Paola, Roig, Roberto, Casamitjana, Natalia, Iudicone, Paola, Schmidt, Michael, Bird, Arthur, Crookes, Robert, Brojer, Ewa, Miceli, Michelina, Amiri, Azin, Li, Chengyao, Allain, Jean-Pierre
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier B.V 01-10-2008; Elsevier
• Subjects: Adult; Aged; Biological and medical sciences; Blood Donors; DNA, Viral - genetics; Epitopes - genetics; Europe; Female; Gastroenterology and Hepatology; Gastroenterology. Liver. Pancreas. Abdomen; Genotype; HBV; Hepatitis B - blood; Hepatitis B - diagnosis; Hepatitis B - ethnology; Hepatitis B virus - genetics; Humans; Male; Medical sciences; Middle Aged; Occult HBV; Prevalence; Viral Envelope Proteins - genetics; Europe; Occult HBV; HBV; Europe; Blood donors; Typing; Orthohepadnavirus; Genotype; Virus; Microbiological investigation; Hepadnaviridae; Gastroenterology; Hepatitis B virus; Blood donor
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2008.04.017

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.