Occult hepatitis B infection in blood donors from South East Asia: molecular characterisation and potential mechanisms of occurrence
- Daniel Candotti1,2,
- C Kit Lin3,
- Dalila Belkhiri2,
- Tasanee Sakuldamrongpanich4,
- Subhajit Biswas2,
- Sujen Lin5,
- Diana Teo6,
- Yasmin Ayob7,
- Jean-Pierre Allain2
- 1National Health Service Blood and Transplant, Cambridge Blood Centre, Cambridge, UK
- 2Department of Haematology, Cambridge Blood Centre, Cambridge, UK
- 3Hong Kong Red Cross Blood Transfusion Centre, Hong Kong, PRC
- 4National Blood Centre, Thai Red Cross Society, Bangkok, Thailand
- 5Taiwan Blood Services Foundation, Taipei, Taiwan
- 6Centre for Transfusion Medicine, Health Science Authority, Singapore
- 7National Blood Centre, Kuala Lumpur, Malaysia
- Correspondence to Professor Jean-P Allain, Department of Haematology, Cambridge Blood Centre, Long Road, Cambridge CB2 2PT, UK;
Contributors DC and J-PA designed and supervised the study, and wrote the manuscript. DC and DB performed the molecular characterisation of the samples, and DC performed the genetic analysis of the viral sequences. CKL, TS, SL, DT and YA selected and collected the blood samples, and performed the HBV serological investigations in the samples. SB and DC produced the HBsAg constructs and performed the cell transfection experiments. All authors contributed to the final version of the manuscript.
- Revised 9 December 2011
- Accepted 10 December 2011
- Published Online First 20 January 2012
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 OBIB (44%) and OBIC (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.
- Hepatitis B virus
- occult HBV infection
- blood donors
- RNA splicing
- diagnostic virology
- hepatitis C
- hepatitis B
- molecular epidemiology
- chronic viral hepatitis
- hepatitis D
- hepatitis E
Funding This study was supported by grants from the International Society of Blood Transfusion Foundation, the National Health Service Blood and Transplant, England, and Novartis.
Competing interests None.
Ethics approval Ethics approval was supplied by Hong Kong Red Cross Blood Centre Internal Review Board.
Provenance and peer review Not commissioned; externally peer reviewed.