标题: Occult hepatitis B infection in blood donors from South East Asia: molecular cha [打印本页] 作者: StephenW 时间: 2012-2-1 10:47 标题: Occult hepatitis B infection in blood donors from South East Asia: molecular cha
Gut. 2012 Jan 20. [Epub ahead of print]
Occult hepatitis B infection in blood donors from South East Asia: molecular characterisation and potential mechanisms of occurrence.
Candotti D, Lin CK, Belkhiri D, Sakuldamrongpanich T, Biswas S, Lin S, Teo D, Ayob Y, Allain JP.
Source
Cambridge Blood Centre, Cambridge, UK.
Abstract
ObjectiveTo 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.ConclusionsThere 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. 作者: StephenW 时间: 2012-2-1 10:47
Curr Opin Hematol. 2011 Nov;18(6):461-6.
Challenges in hepatitis B detection among blood donors.Allain JP, Cox L.
SourceDepartment of Haematology, University of Cambridge, Cambridge, UK. [email protected]
AbstractPURPOSE OF REVIEW: The availability of hepatitis B virus (HBV) nucleic acid testing (NAT) for donor blood screening led to its implementation in low prevalence and high prevalence countries. Genomic detection was a substantial addition to HBV surface protein (HBsAg) screening by detecting window period infections and 'occult' HBV infections (OBIs), characterized by undetectable HBsAg, low viral load and presence of serological markers (anti-HBc and/or anti-HBs). OBIs are the result of multiple, poorly understood mechanisms including incomplete immune control mutations of the HBsAg antigenic determinants; abnormal expression of S gene; and inhibition of genome transcription. Infectivity for the recipient is high for window period blood and relatively low for OBIs.
RECENT FINDINGS: The number of cases identified by NAT ranges between 1 : 1000 and 1 : 50 000, depending on epidemiology and assay sensitivity whether NAT is implemented in individual donations or pools of samples. OBI donors are generally older than 45 years except in Africa, carry very low viral load (median 11-25 IU/ml) and have normal alanine transaminase levels. Cases carrying anti-HBc alone are more infectious than those with low level of anti-HBs. Evidence of HBsAg escape mutants that are undetected by commercial assays has been published. Inhibition of HBsAg mRNA production and export are potential mechanisms of OBI occurrence.
SUMMARY: HBV blood safety is improved by NAT for HBV DNA when applied to individual donations. Until the sensitivity of NAT is improved, both this method and HBsAg screening are needed to eliminate potentially infectious blood donations. Occult HBV characterization clarifies new facets of HBV natural history.