Correlation between the promoter basal core and precore mutations and HBsAg quantification in French blood donors infected with hepatitis B virus

International audienceHepatitis B virus (HBV) basal core promoter (BCP) and precore (PC) mutations, HBV viral load and HBV surface antigen (HBsAg) quantitation were screened to assess correlations between these HBV markers in asymptomatic chronic hepatitis B carriers in France. From January 2006 to July 2007, 200 sera were collected from patients who were discovered to be HBsAg-positive when they volunteered to give blood. Direct sequencing of precore/core gene was used to detect A1762T/G1764A mutations in the BCP and G1896A in the PC region. HBV viral load and HBsAg were quantified with two commercials assays. The prevalence of the BCP and PC mixed/mutants were 37% and 60% respectively (P = 0.0001). HBV DNA level and HBsAg titer were significantly lower in subjects harboring the mixed/mutant PC virus compared to those infected by the wild phenotype. No significant difference was observed in HBV viral loads of blood donors infected by wild or mixed/mutant BCP viruses. Mutant or mixed PC virus was associated with male gender, HBeAb-positive status and HBV/D and HBV/E genotypes. BCP mutations were associated with age, and both HBV/A-HBV/E genotypes.The genetic properties of HBV in this cohort showed that most of the blood donors had a negative HBeAg serological status and harbored the PC mutant phenotype in combination with low levels of both HBV DNA and HBsAg. As the study was conducted in healthy subjects who could be considered as asmptomatic carriers, these results suggest a possible protective effect of the G1896A mutation against severe liver lesions. J. Med. Virol. 87:529–535, 2015. © 2014 Wiley Periodicals, Inc

Résultats de trois méthodes pour la détection de la mutation précore G1896A du virus de l’hépatite B chez les donneurs de sang français : PCR temps réel, séquençage et test Inno-LIPA

AIM: To screen hepatitis B virus (HBV) genotypes and associated basal core promoter (BCP; T1762A/A1764) and precore (PC; A1896) mutations among the 100 HBV surface antigen (HBsAg) positive voluntary blood donors in France. METHODS: HBV genotypes were determined by using direct sequence analysis. Three methods were used to detect G1896A mutation: non-commercial real-time PCR (PCRTR°, line probe assay (InnoLiPA HBV PreCore, INNOGENETICS(®)) and direct sequencing of precore gene. HBV viral load was quantified with two commercial real-time PCR (COBAS(®) AmpliPrep/COBAS(®) TaqMan(®) HBV Test/Roche and Real Time HBV/M2000/Abbott). RESULTS: The mean age of donors was 30 (18-64). Patients were from Africa (42%), Europa (50%), and Asia (8%). HBV/D was the most predominant (37%) genotype followed by HBV/A (31%) and HBV/E (22%). PC and BCP mutants were found in 57% with Inno-LIPA HBV test and 59% with both PCRTR and sequencing methods. A significant difference in the viral load of blood donors with wild and PC mutants was observed with the Taqman Cobas real time PCR (3,19 Log(10) UI/ml versus 4,93 Log(10) UI/ml, p < 0.05). Precore phenotype determination was in agreement with the three PC mutation detection methods in 56% of cases. CONCLUSIONS: Non-Caucasian genotype E was present in the French blood donors. PC mutation was more common than BCP mutations in this study. As HBV infected blood donors were more often asymptomatic carriers, we could speculate that the G1896A mutation may favour the asymptomatic state, supporting previous observations

Human immunodeficiency virus type 1 incidence among blood donors in France, 1992 through 2006: use of an immunoassay to identify recent infections

BACKGROUND: In France, blood donations found to be positive for the presence of human immunodeficiency virus type 1 (HIV-1) are further tested to detect recent infections (≤180 days) using an enzyme immunoassay (EIA-RI) developed in 2002. The characteristics of recently infected donors, estimates of HIV-1 incidence, and the residual risk of transfusion-transmitted HIV-1 are presented, in both first-time and repeat donors. STUDY DESIGN AND METHODS: Of the 1027 donations found to be HIV-1–positive between 1992 and 2006, a total of 459 could be retrospectively tested with the EIA-RI. Multivariate analysis was performed to determine the donor characteristics associated with recent infection. Incidence rates and residual risk obtained with the EIA-RI were compared to classical cohort estimates derived from repeat donor histories. RESULTS: Of the 459 HIV-1–positive donors studied, 105 (22.9%; 95% confidence interval [CI], 19.2-27.0) were identified as recently infected. Factors independently associated with recent infection were repeat donor status (adjusted odds ratio [AOR], 4.0; 95% CI, 2.4-6.9) and non-B subtypes (AOR, 2.0; 95% CI, 1.2-3.6). Incidence decreased from 4.3 (95% CI, 1.9-9.4) in 1992 through 1994 to 1.3 (95% CI, 0.6-2.8) per 105 in 2004 through 2006 in first-time donors and from 3.2 (95% CI, 2.0-5.0) to 0.8 (95% CI, 0.4-1.4) per 105 in repeat donors. Incidence and residual risk estimates were similar to those obtained with the classical cohort method. CONCLUSION: This study suggests that the EIA-RI can be used to estimate HIV-1 incidence in a population with low HIV incidence. The estimated HIV-1 incidence in the blood donor population confirms the extremely low risk (1 in 3,350,000 donations) of HIV-infected blood donations entering the blood supply in France

False-Positive Human Immunodeficiency Virus Enzyme Immunoassay Results in Pregnant Women

Objective: Examine whether false-positive HIV enzyme immunoassay (EIA) test results occur more frequently among pregnant women than among women who are not pregnant and men (others). Design: To obtain a large number of pregnant women and others tested for HIV, we identified specimens tested at a national laboratory using Genetic Systems HIV-1/HIV-2 Plus O EIA from July 2007 to June 2008. Methods: Specimens with EIA repeatedly reactive and Western blot-negative or indeterminate results were considered EIA false-positive. We compared the false-positive rate among uninfected pregnant women and others, adjusting for HIV prevalence. Among all reactive EIAs, we evaluated the proportion of false-positives, positive predictive value (PPV), and Western blot bands among indeterminates, by pregnancy status. Results: HIV prevalence was 0.06 % among 921,438 pregnant women and 1.34 % among 1,103,961 others. The false-positive rate was lower for pregnant women than others (0.14 % vs. 0.21%, odds ratio 0.65 [95 % confidence interval 0.61, 0.70]). Pregnant women with reactive EIAs were more likely than others (p,0.01) to have Western blot-negative (52.9 % vs. 9.8%) and indeterminate results (17.0 % vs. 3.7%) and lower PPV (30 % vs. 87%). The p24 band was detected more often among pregnant women (p,0.01). Conclusions: False-positive HIV EIA results were rare and occurred less frequently among pregnant women than others

A revised method for estimating hepatitis B virus transfusion residual risk based on antibody to hepatitis B core antigen incident cases

BACKGROUND: To take into account the transient nature of hepatitis B virus (HBV) antigenemia, the calculation of HBV residual risk (RR), based on the incidence/window period model, is adjusted by a correction factor that adds uncertainty to the RR estimates. STUDY DESIGN AND METHODS: This new method to estimate the RR for HBV is a weighted sum of the RR derived from hepatitis B surface antigen (HBsAg) incident cases and the one derived from antibody hepatitis B core antigen (HBc) incident cases. An anti-HBc incident case was defined as a donation from a blood donor who had made at least one anti-HBc–negative donation followed by a donation that was found positive with two different assays within a 3-year period and positive for at least one of the following markers: 1) antibody to hepatitis B e antigen or hepatitis B e antigen, 2) anti-HBc immunoglobulin M, 3) HBV DNA, 4) hepatitis B surface antibody without HBV vaccination history, or 5) HBV DNA retrospectively found in the previous donation. Five overlapping 3-year study periods between 2000 and 2006 were analyzed. RESULTS: The HBV RR estimated with the classical method ranged from 1.51 (2000-2002) to 0.69 per million donations in 2004 through 2006 with a decrease in 2002 through 2004 due to only two HBsAg incident cases reported in this period. By applying the revised model, the HBV RR ranged from 1.06 (2000-2002) to 0.49 per million donations (2004-2006), with a regular decrease. CONCLUSION: The new presented model provides HBV RR estimates that do not statistically differ from those obtained with the classical model; however, it provides more accurate data, especially in low endemic areas where the HBsAg incidence is low

Evolutionary history of hepatitis C virus genotype 5a in France, a multicenter ANRS study

The epidemic history of HCV genotype 5a is poorly documented in France, where its prevalence is very low, except in a small central area, where it accounts for 14.2% of chronic hepatitis C cases. A Bayesian coalescent phylogenetic investigation based on the E1 envelope gene and a non-structural genomic segment (NS3/4) was carried out to trace the origin of this epidemic using a large sample of genotype 5a isolates collected throughout France. The dates of documented transmissions by blood transfusion were used to calibrate five nodes in the phylogeny. The results of the E1 gene analysis showed that the best-fitting population dynamic model was the expansion growth model under a relaxed molecular clock. The rate of nucleotide substitutions and time to the most recent common ancestors (tMRCA) of genotype 5a isolates were estimated. The divergence of all the French HCV genotype 5a strains included in this study was dated to 1939 [95% HPD: 1921–1956], and the tMRCA of isolates from central France was dated to 1954 [1942–1967], which is in agreement with epidemiological data. NS3/4 analysis provided similar estimates with strongly overlapping HPD values. Phylodynamic analyses give a plausible reconstruction of the evolutionary history of HCV genotype 5a in France, suggesting the concomitant roles of transfusion, iatrogenic route and intra-familial transmission in viral diffusion

Effectiveness of treatment with pegylated interferon and ribavirin in an unselected population of patients with chronic hepatitis C: A Danish nationwide cohort study

<p>Abstract</p> <p>Background</p> <p>The effect of peginterferon and ribavirin treatment on chronic hepatitis C virus (HCV) infection has been established in several controlled clinical studies. However, the effectiveness of treatment and predictors of treatment success in routine clinical practice remains to be established. Our aim was to estimate the effectiveness of peginterferon and ribavirin treatment in unselected HCV patients handled in routine clinical practice. The endpoint was sustained virological response (SVR), determined by the absence of HCV RNA 24 weeks after the end of treatment.</p> <p>Methods</p> <p>We determined the proportion of SVR in a nationwide, population-based cohort of 432 patients with chronic HCV infection who were starting treatment, and analyzed the impact of known covariates on SVR by using a logistic regression analysis.</p> <p>Results</p> <p>The majority of treated patients had genotype 1 (133 patients) and genotype 2/3 (285 patients) infections, with 44% and 72%, respectively, obtaining SVR. Other than genotype, the predictors of SVR were age ≤ 45 years at the start of treatment, completion of unmodified treatment, the absence of cirrhosis and non-European origin.</p> <p>Conclusions</p> <p>The effectiveness of peginterferon and ribavirin treatment for chronic hepatitis C in a routine clinical practice is comparable to that observed in controlled clinical trials, with a higher SVR rate in genotype 2 and 3 patients compared to genotype 1 patients. Our data further indicate that age at start of treatment is a strong predictor of SVR irrespective of HCV genotype, with patients 45 years or younger having a higher SVR rate.</p

Harnessing difference: a capability-based framework for stakeholder engagement in environmental innovation

Innovation for environmental sustainability requires firms to engage with external stakeholders to access expertise, solve complex problems, and gain social legitimacy. In this open innovation context, stakeholder engagement is construed as a dynamic capability that can harness differences between external stakeholders to augment their respective resource bases. An integrative systematic review of evidence from 88 scientific articles finds that engaging stakeholders in environmental innovation requires three distinct levels of capability: specific operational capabilities; first-order dynamic capabilities to manage the engagement (engagement management capabilities); and second-order dynamic capabilities to make use of contrasting ways of seeing the world to reframe problems, combine competencies in new ways, and co-create innovative solutions (value framing), and to learn from stakeholder engagement activities (systematized learning). These findings enhance understanding of how firms can effectively incorporate stakeholder perspectives for environmental innovation, and provide an organizing framework for further research into open innovation and co-creation more broadly. Wider contributions to the dynamic capabilities literature are to (i) offer a departure point for further research into the relationship between first-order and second-order dynamic capabilities, (ii) suggest that institutional theory can help explain the dynamic capability of value framing, (iii) build on evidence that inter-institutional learning is contingent on not only the similarity but also the differences between organizational value frames, and (iv) suggest that operating capabilities impact the effectiveness of dynamic capabilities, rather than only the other way around, as is usually assumed. A methodological contribution is made through the application of quality assessment criteria scores and intercoder reliability statistics to the selection of articles included in the systematic review

Harnessing difference: a capability-based framework for stakeholder engagement in environmental innovation

Innovation for environmental sustainability requires firms to engage with external stakeholders to access expertise, solve complex problems, and gain social legitimacy. In this open innovation context, stakeholder engagement is construed as a dynamic capability that can harness differences between external stakeholders to augment their respective resource bases. An integrative systematic review of evidence from 88 scientific articles finds that engaging stakeholders in environmental innovation requires three distinct levels of capability: specific operational capabilities; first-order dynamic capabilities to manage the engagement (engagement management capabilities); and second-order dynamic capabilities to make use of contrasting ways of seeing the world to reframe problems, combine competencies in new ways, and co-create innovative solutions (value framing), and to learn from stakeholder engagement activities (systematized learning). These findings enhance understanding of how firms can effectively incorporate stakeholder perspectives for environmental innovation, and provide an organizing framework for further research into open innovation and co-creation more broadly. Wider contributions to the dynamic capabilities literature are to (i) offer a departure point for further research into the relationship between first-order and second-order dynamic capabilities, (ii) suggest that institutional theory can help explain the dynamic capability of value framing, (iii) build on evidence that inter-institutional learning is contingent on not only the similarity but also the differences between organizational value frames, and (iv) suggest that operating capabilities impact the effectiveness of dynamic capabilities, rather than only the other way around, as is usually assumed. A methodological contribution is made through the application of quality assessment criteria scores and intercoder reliability statistics to the selection of articles included in the systematic review