Occult hepatitis B infection in blood donors from South East Asia: molecular cha

StephenW

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.

StephenW

肠道。 2012年1月20日。 [检索提前打印]
隐匿性乙肝病毒感染献血者来自东南亚的分子特性和发生的潜在机制。
Candotti研发，林CK，Belkhiri ð，Sakuldamrongpanich T，比斯瓦斯小号，林士杰，张志贤ð，Ayob Ÿ，Allain JP。
来源

，英国剑桥，剑桥大学血液中心。
摘要

目的探讨隐匿性乙型肝炎病毒（HBV）感染（OBI）亚洲献血者的分子基础。
设计
HBV血清学标志物，以及来自香港，马来西亚，新加坡，台湾和泰国的欧倍德捐助者进行了测试株的分子特征。
结果
在138个确认的欧倍德运营商（平均年龄47岁），HBV基因型B和C为主（分别为60％和34％）同意在该地区的长期感染者的基因型分布。病毒载量无法量化和3670 IU /毫升之间不等（中位数为11国际单位/毫升）。 OBIS百分之十一％表明，没有证据表明这些人大部分过去接种疫苗的抗- HBs只血清学一个不寻常的个人资料。隐匿性HBV株表现出比菌株匹配的乙肝表面抗原（HBsAg）+捐助者，不论基因型的遗传多样性较高。没有独特的基因签名或复制能力降低的证据被发现。在欧倍德（二）（44％），欧倍德（三）株（36％），前S2 / S的剪接捐助现场附近的突变是共同的。来自四个欧倍德案件小号地区分别转染Huh7肝癌细胞。结果表明：有限HBsAg的分泌和建议，前S2 / S的表达splicing.ConclusionsThere是间接证据，不完整的免疫控制是涉及欧倍德在亚洲血液，B和C基因型感染者发生突变破坏剪接捐助网站的结构，可能会影响在欧洲观察基因型A2，但程度较低的一个转录后机制可能发挥比D基因型HBV基因型在某些海洋生物地理信息系统，不论在HBsAg的表达的作用。

StephenW

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.

StephenW

CURR OPIN血液学。2011月;18（6）:461- 6。
在B型肝炎检测献血者之间的挑战。
Allain太平绅士，考克斯L。
来源

血液学系，剑桥大学，英国剑桥。 [email protected]
摘要
目的审查：

乙型肝炎病毒（HBV）的核酸检测（NAT）的捐赠者的血液筛查的可用性，导致其执行在低发病率和高发病率国家。基因检测是一项重大的除了乙肝病毒表面蛋白（HBsAg）的检测窗口期感染和“隐匿性HBV感染（OBIS），乙肝表面抗原检测不到，低病毒载量和存在的血清学标志物（抗- HBc和/或抗的特点，筛选- HBS）。 OBIS是多个，知之甚少的机制，包括不完整的乙肝表面抗原的抗原决定簇的免疫控制突变的结果; S基因的异常表达和基因组的转录抑制。收件人的传染性是窗口期血液高和相对低OBIS。
最近的调查结果：

NAT所鉴定的案件数目为1：1000和1：50000间，取决于是否实施NAT是在个人捐款或样品池的流行病学和检测的灵敏度。欧倍德捐助者一般都是45岁以上，除在非洲，进行病毒载量非常低（中位数11-25国际单位/毫升）和谷丙转氨酶水平正常。携带抗- HBc阳性单独的个案，较抗- HBs水平低的传染性。 HBsAg的商业分析未被发现的逃避突变的证据已经出版。抑制乙肝表面抗原mRNA的生产和出口欧倍德发生的潜在机制。
摘要：

HBV - DNA乙肝病毒的血液安全是改善通过NAT时，适用于个人捐款。直到改进的NAT的敏感性，这种方法和HBsAg筛查，以消除潜在的传染性的献血。隐匿性HBV表征阐明HBV的自然史的新的方面。

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