Objective: To investigate the molecular basis of occult hepatitis B virus (HBV) infection (OBI) in Asian blood donors.
Design: OBI donors from Hong Kong, Malaysia, Singapore, Taiwan and Thailand were tested for HBV serological markers, and strains were molecularly characterised.
Results: Among 138 confirmed OBI carriers (median age 47 years), HBV genotypes B and C were dominant (60% and 34%, respectively) in agreement with the genotype distribution in chronically infected donors in the region. Viral load ranged between unquantifiable and 3670 IU/ml (median 11 IU/ml). Eleven per cent of OBIs showed an unusual anti-HBs-only serological profile without evidence of past vaccination for most of these individuals. Occult HBV strains showed a higher genetic diversity than strains from matched hepatitis B surface antigen (HBsAg)+ donors, irrespective of genotype. No unique genetic signature or evidence of reduced replication competence was found. Mutations in the vicinity of the pre-S2/S splice donor site were common in OBI(B) (44%) and OBI(C) (36%) strains. S regions from four OBI cases were transfected in HuH7 cells. Results showed limited HBsAg secretion and suggested that mutations disrupting the splice donor site structure may affect pre-S2/S mRNA splicing.
Conclusions: There is indirect evidence that incomplete immune control is involved in the occurrence of OBI in Asian blood donors infected with genotypes B and C as observed in Europe with genotype A2 but to a lower extent than with genotype D. A post-transcriptional mechanism may play a role in HBsAg expression in some OBIs irrespective of HBV genotype.