Occult hepatitis B infection in blood donors from South East Asia: molecular characterisation and potential mechanisms of occurrence

Candotti, Daniel; Lin, Che Kit; Belkhiri, Dalila; Sakuldamrongpanich, Tasanee; Biswas, Subhajit; Lin, Sujen; Teo, Diana; Ayob, Yasmin; Allain, Jean‐Pierre

doi:10.1136/gutjnl-2011-301281

Cited by 98 publications

(147 citation statements)

References 31 publications

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“…OBI is a potential source of HBV transmission by transfusion and organ transplantation, can reactivate in association with immunodeficiency or immunosuppressive treatments, and might be a risk factor for liver cancer (2). Several mechanisms have been proposed as responsible for OBI, such as imperfect control by the host immune system (3,4), multiple amino acid substitutions in the S protein affecting HBsAg detection with commercial immunoassays (5,6), mutations in regulatory elements negatively affecting virus replication (7,8), and mutations affecting posttranscriptional mechanisms regulating S protein expression (9,10).…”

Section: O Ccult Hepatitis B Virus (Hbv) Infection/carriage (Obi) Ismentioning

confidence: 99%

Specific Amino Acid Substitutions in the S Protein Prevent Its Excretion In Vitro and May Contribute to Occult Hepatitis B Virus Infection

Biswas

Candotti

Allain

2013

J Virol

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bOccult hepatitis B virus (HBV) infection (OBI) is defined as low plasma level of HBV DNA with undetectable HBV surface antigen (HBsAg) outside the preseroconversion window period. The mechanisms leading to OBI remain largely unknown. The potential role of specific amino acid substitutions in the S protein from OBI in HBsAg production and excretion was examined in vitro. HBsAg was quantified in culture supernatants and cell extracts of HuH-7 cells transiently transfected with plasmids containing the S gene of eight HBsAg ؉ controls and 18 OBI clones. The intracellular (IC)/extracellular (EC) HBsAg production ratio was ϳ1.0 for the majority of controls. Three IC/EC HBsAg patterns were observed in OBI strains clones: pattern 1, an IC/EC ratio of 1.0, was found in 5/18 OBI clones, pattern 2, detectable IC but low or undetectable EC HBsAg (IC/EC, 7.0 to 800), was found in 6/18 OBIs, and pattern 3, low or undetectable IC and EC HBsAg, was found in 7/18 clones. Intracellular immunofluorescence staining showed that in pattern 2, HBsAg was concentrated around the nucleus, suggesting retention in the endoplasmic reticulum. The substitution M75T, Y100S, or P178R was present in 4/6 pattern 2 OBI clones. Site-directed-mutagenesis-corrected mutations reversed HBsAg excretion to pattern 1 and, when introduced into a control clone, induced pattern 2 except for Y100S. In a control and several OBIs, variants of a given quasispecies expressed HBsAg according to different patterns. However, the P178R substitution present in all cloned sequences of two OBI strains may contribute significantly to the OBI phenotype. O ccult hepatitis B virus (HBV) infection/carriage (OBI) ischaracterized by the presence of very low levels of HBV DNA in plasma and/or in liver with hepatitis B surface antigen (HBsAg) being undetectable using the most sensitive commercial assays, with or without antibodies to hepatitis core antigen (anti-HBc) or hepatitis B surface antigen (anti-HBs), outside the preseroconversion window period (1). OBI represents a particular form of persistent or chronic infection that is encountered globally, albeit at different frequencies depending on endemicity and genotype (2). OBI is a potential source of HBV transmission by transfusion and organ transplantation, can reactivate in association with immunodeficiency or immunosuppressive treatments, and might be a risk factor for liver cancer (2). Several mechanisms have been proposed as responsible for OBI, such as imperfect control by the host immune system (3, 4), multiple amino acid substitutions in the S protein affecting HBsAg detection with commercial immunoassays (5, 6), mutations in regulatory elements negatively affecting virus replication (7, 8), and mutations affecting posttranscriptional mechanisms regulating S protein expression (9, 10).A high frequency of mutations has been observed especially within the major hydrophilic region (MHR) of S protein from OBI strains, and these may alter antigenicity, HBV infectivity, cell tropism, and virion morphogenesis (4-6, 11). In...

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Section: O Ccult Hepatitis B Virus (Hbv) Infection/carriage (Obi) Ismentioning

confidence: 99%

Specific Amino Acid Substitutions in the S Protein Prevent Its Excretion In Vitro and May Contribute to Occult Hepatitis B Virus Infection

Biswas

Candotti

Allain

2013

J Virol

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“…Introducing HBV NAT is more favorable in high-endemic areas, where OBI prevalence is high, compared to those with low to medium endemicity of HBV infection. The disadvantage of not implementing NAT testing is the risk of transfusion blood unit from a donor in the window period and in seronegative (anti HBc negative) OBI donors (46). A better strategy of screening should be reconsidered to decrease the number of blood deferrals in Lebanon such as serological testing of both anti HBc followed by anti-HBs or implementation of NAT along with anti-HBc.…”

mentioning

confidence: 99%

Low Prevalence of Occult Hepatitis B Infection Among Blood Donors in Beirut, Lebanon: Reconsider the Deferral Strategy of Anti-HBc Positive Blood Donors

et al. 2017

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Background: Hepatitis B virus (HBV) infection remains one of the major infectious threats to human health. Since the implementation of highly sensitive HBV nucleic acid testing, occult HBV infection (OBI) has been detected. Occult HBV infection is characterized by a positive HBV DNA test with undetectable HBsAg (Hepatits B surface antigen). The prevalence of OBI varies significantly between geographic areas, genotypes, and population depending on the sensitivity of the detection assays used.

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“…This could be possibly attributed to escape mutations which could have altered the target epitope(s) of the HBsAg assay [48] . A recent study of OBI in Asian blood donors showed a viral load range between unquantifiable and 3670 IU/mL with a median 11 IU/ mL [49] . In humans, HBV transmission was reported from donors in the window period and OBI donors showing HBV DNA load < 20 IU/mL [7,34,50] .…”

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confidence: 99%

Occult hepatitis B virus infection among Egyptian blood donors

Said

Sayed²,

Salama

et al. 2013

WJH

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AIM:To identify blood donors with occult hepatitis B virus (HBV) infection (OBI) to promote safe blood donation. METHODS:Descriptive cross sectional study was conducted on 3167 blood donors negative for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab) and human immunodeficiency virus Ab. They were subjected to the detection of alanine aminotransferase (ALT) and aspartate transaminase (AST) and screening for anti-HBV core antibodies (total) by two different techniques; [Monoliza antibodies to hepatitis B core (Anti-HBc) Plus-Bio-Rad] and (ARC-HBc total-ABBOT). Positive samples were subjected to quantitative detection of antibodies to hepatitis B surface (anti-HBs) (ETI-AB-AUK-3, Dia Sorin-Italy). Serum anti-HBs titers > 10 IU/L was considered positive. Quantitative HBV DNA by real time polymerase chain reaction (PCR) (QIAGEN-Germany) with 3.8 IU/mL detection limit was estimated for blood units with negative serum anti-HBs and also for 32 whose anti-HBs serum titers were > 1000 IU/L. Also, 265 recipients were included, 34 of whom were followed up for 3-6 mo. Recipients were investigated for ALT and AST, HBV serological markers: HBsAg (ETI-MAK-4, Dia Sorin-Italy), anti-HBc, quantitative detection of anti-HBs and HBV-DNA. RESULTS: 525/3167 (16.6%) of blood units were positive for total anti-HBc, 64% of those were antiHBs positive. Confirmation by ARCHITECT anti-HBc assay were carried out for 498/525 anti-HBc positive samples, where 451 (90.6%) confirmed positive. Reactivity for anti-HBc was considered confirmed only if two positive results were obtained for each sample, giving an overall prevalence of 451/3167 (14.2%) for total anti-HBc. HBV DNA was quantified by real time PCR in 52/303 (17.2%) of anti-HBc positive blood donors (viral load range: 5 to 3.5 x 10 5

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Occult hepatitis B infection in blood donors from South East Asia: molecular characterisation and potential mechanisms of occurrence

Cited by 98 publications

References 31 publications

Specific Amino Acid Substitutions in the S Protein Prevent Its Excretion In Vitro and May Contribute to Occult Hepatitis B Virus Infection

Specific Amino Acid Substitutions in the S Protein Prevent Its Excretion In Vitro and May Contribute to Occult Hepatitis B Virus Infection

Low Prevalence of Occult Hepatitis B Infection Among Blood Donors in Beirut, Lebanon: Reconsider the Deferral Strategy of Anti-HBc Positive Blood Donors

Occult hepatitis B virus infection among Egyptian blood donors

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