RESUMEN
Patients living with HIV infection (PLWH) are at risk of acquiring HBV and HDV. The present study aimed to determine the prevalence and characteristics of HIV-HDV-HBV tri-infection in comparison with HIV-HBV coinfection and to estimate severities and outcomes of associated liver diseases in Mauritanian PLWH. Two-hundred-ninety-two consecutive HBsAg-positive PLWH were included (mean age: 37 years). Clinical data were recorded. Anti-HDV antibodies, HBV and HDV viral loads (VLs) and genotype were determined. APRI, FIB-4 and FibroScan were performed to evaluate the severity of liver disease. The anti-HDV antibodies prevalence was 37% and HDV RNA was positive in 40.7% of patients. Genetic diversities were found with HDV genotype 1 (93%) and HBV genotypes D (42.5%) and E (38%). The HBV VL was detectable in 108 patients at inclusion, and mutations associated with HBV resistance were found in 20. For almost all variables studied, including FIB-4 and APRI scores, no significant differences were found between anti-HDV-Ab positive or negative patients. FibroScan examination, which was performed in 110 patients at end-of-follow-up showed higher, but NS values, in HDV positive patients. After a mean follow-up of 24.55 ± 8.01 months (n = 217 patients), a highly significant worsening of APRI and FIB-4 scores was found. Moreover, patients with HDV showed more severe liver disease progression despite an efficient therapy. In a substantial Mauritanian cohort of relatively young PLWH, we found high HDV prevalence and worsening liver disease. In high-risk countries, screening for HDV and providing appropriate follow-up and treatments are warranted in PLWH.
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Coinfección , Infecciones por VIH , Anticuerpos Antihepatitis , Hepatitis D , Virus de la Hepatitis Delta , Carga Viral , Humanos , Mauritania/epidemiología , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Masculino , Adulto , Femenino , Prevalencia , Virus de la Hepatitis Delta/genética , Anticuerpos Antihepatitis/sangre , Coinfección/epidemiología , Coinfección/virología , Hepatitis D/epidemiología , Hepatitis D/complicaciones , Persona de Mediana Edad , Pronóstico , Hepatitis B/epidemiología , Hepatitis B/complicaciones , Hepatitis B/virología , Genotipo , Adulto Joven , Virus de la Hepatitis B/genéticaRESUMEN
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights the importance of rapid diagnostic testing to identify individuals with SARS-CoV-2 infections and to limit the spread of the virus. Many molecular assays have become commercially available to cope with this surging demand for timely diagnosis of COVID-19 cases, but identifying individuals requires accurate diagnostic tools. We compared the performance of three molecular SARS-CoV-2 assays: Aptima™ SARS-CoV-2 assay running on the Panther system (Hologic), an in-house assay (Laboratory Developed Test, LDT) running on the Fusion module of the Panther Fusion system (LDT-Fusion; Hologic), and the R-GENE® SARS-CoV-2 assay (bioMérieux). In addition, we also evaluated the turnaround time. This parameter is crucial to managing the SARS-CoV-2 diagnosis and represents a key point in the quality management at the laboratory. Aptima™ and LDT-Fusion assays exhibited an excellent positive percent agreement (PPA) (100.0%), while the R-GENE® assay showed a slightly decreased PPA (98.2%). The Hologic assays have a higher throughput with less hands-on time than the R-GENE® assays (24-25 vs. 71 min). Both Hologic assays are used on a fully automated random-access testing system with on-demand testing capabilities that avoid run series, unlike the R-GENE® assay. Automated random-access testing systems should be preferred during periods of high SARS-CoV-2 prevalence.
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COVID-19 , SARS-CoV-2 , COVID-19/diagnóstico , Prueba de COVID-19 , Humanos , SARS-CoV-2/genética , Sensibilidad y EspecificidadRESUMEN
Background Our laboratory obtained the ISO 15189 accreditation for the plasmatic HIV-1, HBV and HCV viral load (VL) using the m2000 RealTime™ system, which was recently changed for the platform Panther®. Here, we discuss a strategy for performing method validation/verification very quickly. Methods We performed the mandatory (repeatability, internal quality assessment [IQA], measurement uncertainty [MU]) and optional technical verifications for CE/IVD assays using the flexible scope range A. We also performed the mandatory assays for the validation of HIV-1 VL in the cerebrospinal fluid (CSF) using the flexible scope range B. The change was checked by following up on the turnaround time (TAT). Results The coefficient of variation (CV%) for repeatability and IQA complied with the limit of 0.25 log. The MU results ranged from 0.04 to 0.25 log copies or IU/mL. The comparisons of methods showed excellent correlations (R2 = 0.96 for the three parameters) but a delayed centrifugation on HCV VL showed variations of up to 2 log IU/mL. An excellent linearity for HIV-1 in the CSF was obtained from 1.5 to 5 log copies/mL with R2 = 0.99. The TAT increased (84%-98%) in routine usage. Conclusions The three Aptima assays are well suited for routine laboratory use and can be integrated within less than 2 weeks in accordance with flexible scope range A. Our data allows us to confidently perform HIV-1 VL in CSF following flexible scope range B. Finally, we provide an organizational guide for flexible scope management in molecular virology within a short time frame.
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VIH-1/genética , Hepacivirus/genética , Virus de la Hepatitis B/genética , Técnicas de Diagnóstico Molecular/normas , ARN Viral/normas , Infecciones de Transmisión Sanguínea/diagnóstico , Infecciones de Transmisión Sanguínea/virología , VIH-1/aislamiento & purificación , Hepacivirus/aislamiento & purificación , Virus de la Hepatitis B/aislamiento & purificación , Humanos , Técnicas de Diagnóstico Molecular/métodos , ARN Viral/sangre , ARN Viral/líquido cefalorraquídeo , Juego de Reactivos para Diagnóstico , Reacción en Cadena en Tiempo Real de la Polimerasa , Reproducibilidad de los Resultados , Carga Viral , Productos del Gen pol del Virus de la Inmunodeficiencia Humana/genéticaRESUMEN
BACKGROUND: Ribavirin exposure after the first dose (D0AUC0-4h) >1755 mcg·h·L is predictive of sustained virological response (SVR) in patients with hepatitis C treated with peginterferon and ribavirin. The aim of this study was to test the benefit of ribavirin early dose adjustment based on this target in naïve patients infected with genotype 1. METHODS: A multicenter randomized controlled trial with two parallel groups; fixed-dose (FD) group: standard of care in 2010-2011, ie, peginterferon-α2a 180 mcg·wk and weight-based ribavirin 1000-1200 mg/d during 48 weeks; adapted-dose (AD) group: increase of ribavirin dose if D0AUC0-4h <1755 mcg·h·L. RESULTS: A total of 221 patients were included, 110 in the AD group and 111 in the FD group with similar baseline characteristics. In the perprotocol analysis, SVR was higher in the AD group (55.1% versus 40.4%; P = 0.042), especially in patients with D0AUC0-4h <1755 mcg·h·L (54.3% versus 31.9%; P = 0.029). In the intention-to-treat analysis, the difference was not significant (50% versus 41%; P = 0.197). Ribavirin trough concentrations (C0s) at week 4 of treatment (intention-to-treat analysis) were higher in patients achieving SVR (2.06 versus 1.72 mg/L, P = 0.003). In the subgroup of patients with AUC0-4h <1755 mcg·h·L, 46% of patients with AD achieved a C0 >2.0 mg/L versus 22% of patients with FD (P = 0.013). Grade 1 anemia (but not other grades) was more frequent in the AD group (70% versus 48%, P = 0.001). The number of dose reductions or discontinuation of ribavirin was similar in both groups. CONCLUSIONS: Early ribavirin dose adjustment increases SVR in patients underexposed to ribavirin without increasing grade II-IV anemia. Such a strategy could be useful in patients with no access to new antiviral drugs.
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Antivirales/administración & dosificación , Antivirales/efectos adversos , Hepatitis C/tratamiento farmacológico , Interferones/administración & dosificación , Proteínas Recombinantes/administración & dosificación , Ribavirina/administración & dosificación , Ribavirina/efectos adversos , Adulto , Relación Dosis-Respuesta a Droga , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Ensayos Clínicos Pragmáticos como AsuntoRESUMEN
BACKGROUND AND AIM: The impact of basal core promoter (BCP) and precore (PC) mutants of the hepatitis B virus (HBV) on liver disease severity remains controversial. The aim of the present study was to screen BCP and PC mutations in 252 HBV surface antigen (HBsAg) positive carriers in France and to assess relationships between these mutations and severe fibrosis. METHODS: Direct sequencing of the precore/core gene was used to detect A1762T/G1764A and G1757A mutations in the BCP and G1896A and G1899A mutations in the PC region. RESULTS: The prevalences of A1762T/G1764A, G1757A, G1896A, and G1899A mutations were 34.1%, 38.7%, 54.9%, and 29.3% (P < 0.001), respectively. The independent predictors of severe fibrosis (≥F3 Metavir) were older age (P < 0.001), male gender (P = 0.012), elevated alanine aminotransferase (P < 0.001), and the double A1762T/G1764A mutant with no other mutations (P = 0.011). Interestingly, the association of the G1899A mutation with the double A1762T/G1764A mutant significantly counteracted the deleterious effect of the sole double A1762T/G1764A mutant (odds ratio [OR] = 0.28 vs. OR = 3.55, respectively, P = 0.028). CONCLUSIONS: Patients with the A1762T/G1764A mutation have a higher risk of severe fibrosis. The G1899A mutation is a protective factor against severe fibrosis that counteracted the deleterious effect of the A1762T/G1764A mutation. Finally, host phenotypic and HBV genotypic markers independently predict fibrosis severity.
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Virus de la Hepatitis B/genética , Hepatitis B Crónica/virología , Cirrosis Hepática/virología , Mutación , Adulto , Factores de Edad , Anciano , ADN Viral/análisis , ADN Viral/genética , Femenino , Antígenos de Superficie de la Hepatitis B/genética , Virus de la Hepatitis B/patogenicidad , Hepatitis B Crónica/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Regiones Promotoras Genéticas/genética , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores Sexuales , Virulencia/genéticaRESUMEN
OBJECTIVE: Interleukin-26 (IL-26) is a member of the IL-10 cytokine family, first discovered based on its peculiar expression by virus-transformed T cells. IL-26 is overexpressed in chronic inflammation (rheumatoid arthritis and Crohn's disease) and induces proinflammatory cytokines by myeloid cells and some epithelial cells. We thus investigated the expression and potential role of IL-26 in chronic HCV infection, a pathology associated with chronic inflammation. DESIGN: IL-26 was quantified in a cohort of chronically HCV-infected patients, naive of treatment and its expression in the liver biopsies investigated by immunohistochemistry. We also analysed the ability of IL-26 to modulate the activity of natural killer (NK) cells, which control HCV infection. RESULTS: The serum levels of IL-26 are enhanced in chronically HCV-infected patients, mainly in those with severe liver inflammation. Immunohistochemistry reveals an intense IL-26 staining in liver lesions, mainly in infiltrating CD3+ cells. We also show that NK cells from healthy subjects and from HCV-infected patients are sensitive to IL-26. IL-26 upregulates membrane tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) expression on CD16- CD56(bright) NK cells, enabling them to kill HCV-infected hepatoma cells, with the same efficacy as interferon (IFN)-α-treated NK cells. IL-26 also induces the expression of the antiviral cytokines IFN-ß and IFN-γ, and of the proinflammatory cytokines IL-1ß and TNF-α by NK cells. CONCLUSIONS: This study highlights IL-26 as a new player in the inflammatory and antiviral immune responses associated with chronic HCV infection.
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Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/inmunología , Interferón-alfa/uso terapéutico , Interleucinas/sangre , Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Antivirales/uso terapéutico , Biomarcadores/sangre , Biopsia con Aguja , Antígeno CD56/inmunología , Antígeno CD56/metabolismo , Células Cultivadas/efectos de los fármacos , Células Cultivadas/inmunología , Citocinas/metabolismo , Femenino , Hepatitis C Crónica/sangre , Humanos , Inmunohistoquímica , Células Asesinas Naturales/efectos de los fármacos , Células Asesinas Naturales/inmunología , Masculino , Receptores de IgG/inmunología , Receptores de IgG/metabolismo , Índice de Severidad de la Enfermedad , Estadísticas no ParamétricasRESUMEN
UNLABELLED: Chronic hepatitis C virus (HCV) infection is characterized by progressive hepatic fibrosis, a process dependent on monocyte recruitment and accumulation into the liver. The mediators expressed in chronically injured liver that control the differentiation of human monocytes into profibrotic macrophages (Mφ) remain poorly defined. We report that chronically HCV-infected patients with high fibrosis stages have higher serum levels of macrophage colony-stimulating factor (M-CSF) and interleukin (IL)-34 than HCV-infected patients with lower fibrosis stages and healthy subjects. Immunohistochemistry reveals an intense expression of IL-34 and M-CSF by hepatocytes around liver lesions. In addition, HCV infection and inflammatory cytokines enhance the in vitro production of IL-34 and M-CSF by hepatocytes. We next analyzed the acquisition of profibrotic properties by Mφ generated with M-CSF (M-CSF-Mφ) or IL-34 (IL-34-Mφ). M-CSF and IL-34 up-regulate the expression, by differentiating monocytes, of chemokine (C-C motif) ligand (CCL)2, CCL4, C-C chemokine receptor (CCR)1, and CCR5, which are involved in monocyte recruitment/Mφ accumulation in liver lesions. M-CSF-Mφ and IL-34-Mφ also express the hepatic stellate cell (HSC) activators, platelet-derived growth factor, transforming growth factor beta, and galectin-3. IL-34-Mφ and M-CSF-Mφ induce type I collagen synthesis by HSCs, the main collagen-producing cells in liver fibrosis. IL-13, whose expression correlates with the fibrosis stage in HCV-infected patients, decreases the expression of the collagenase, matrix metalloproteinase 1, by IL-34-Mφ and M-CSF-Mφ, thereby enhancing collagen synthesis. By inhibiting the production of interferon-gamma (IFN-γ) by activated natural killer cells, IL-34-Mφ and M-CSF-Mφ prevent the IFN-γ-induced killing of HSCs. CONCLUSION: These results identify M-CSF and IL-34 as potent profibrotic factors in HCV liver fibrosis.
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Hepatitis C Crónica/complicaciones , Interleucinas/sangre , Cirrosis Hepática/inmunología , Factor Estimulante de Colonias de Macrófagos/sangre , Adulto , Anciano , Estudios de Casos y Controles , Línea Celular , Colágeno Tipo I/biosíntesis , Femenino , Células Estrelladas Hepáticas/metabolismo , Hepatitis C Crónica/metabolismo , Hepatocitos/metabolismo , Humanos , Interferón gamma/metabolismo , Interleucina-13/metabolismo , Células Asesinas Naturales/metabolismo , Cirrosis Hepática/metabolismo , Masculino , Metaloproteinasa 1 de la Matriz/metabolismo , Persona de Mediana EdadRESUMEN
INTRODUCTION: Infection by hepatitis B virus (HBV) is a major issue in public health. The prevalence of HBV in Chad is 12.4%, all age groups considered. Here, we aimed to determine the prevalence of HBV and its associated factors among university students in N'Djamena, the country's capital. METHODS: A cross-sectional survey of students at either the University of N'djamena or Emi Koussi University was conducted from 3 to 23 July 2021. All participating students provided signed, informed consent and were included in the study consecutively. Blood samples were collected, and serum tested for hepatitis B surface antigen (HBsAg) using the Determine HBsAg rapid test kit, with confirmation of positive tests on an Abbott Architect i1000SR analyzer. Descriptive analysis and logistic regression were used to determine associations between the outcome variable and independent/covariate variables. RESULTS: A total of 457 students with a median age of 24 years were included across different faculties. The prevalence of HBV infection was 14.87% (68/457). Most students (75%) were aged 25 years or less. Unprotected sex was reported by 64.9% of the students and multiple sexual partners by 53.6%. Furthermore, 45.7% of them reported having no knowledge of hepatitis B. Having an HBsAg-positive mother (AOR: 2.11), having a history of transcutaneous medical procedures (AOR: 2.97) and living with a family (AOR: 4.63) were significantly associated with HBV status. Age ≥26 years appeared as a protective factor (AOR = 0.41). CONCLUSION: Our study detected a high, 14.87% prevalence of HBV infection among students in N'djamena, Chad, and shed light on its associated factors. HBV prevention strategies should include raising awareness among students, making full hepatitis vaccination mandatory before children begin school, promoting mass screening to identify and treat chronic HBV carriers and reduce transmission, and reducing the cost of vaccination.
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Virus de la Hepatitis B , Hepatitis B , Niño , Femenino , Humanos , Adulto Joven , Adulto , Antígenos de Superficie de la Hepatitis B , Prevalencia , Estudios Transversales , Chad/epidemiología , Hepatitis B/prevención & control , EstudiantesRESUMEN
OBJECTIVES: Widespread testing and treatment are essential to eliminate hepatitis B virus (HBV) infection as a public health concern. However, in resource-limited countries, access to HBV PCR is limited. In this study, we developed a quantitative HBV PCR assay on open molecular platforms and evaluate its performance in diagnosing clinically significant HBV DNA thresholds as defined by the WHO (2000 IU/mL, 20 000 IU/mL, and 200 000 IU/mL). METHODS: We implemented our HBV PCR test in seven African and Asian countries and France, using either an in-house laboratory method or a European conformity for in vitro diagnostic (CE-IVD) marked version of the PCR (Generic HBV Charge Virale, Biocentric). Results were compared with reference tests (Roche Cobas AmpliPrep/Cobas TaqMan and Abbott RealTime on Abbott m2000). RESULTS: There was a good agreement between the HBV DNA results of 1015 samples tested by the PCR on open polyvalent platforms and the results from reference tests (mean difference (bias ± standard deviation [SD]): -0.3 ± 0.7 log10 IU/mL and -0.2 ± 0.9 log10 IU/mL when compared with Roche and Abbott tests, respectively). Kappa-Cohen agreements between the HBV PCR on open polyvalent platforms and the Roche/Abbott assays appeared almost perfect for HBV DNA levels ranged from >20 000 to 200 000 IU/mL and >200 000 IU/mL, substantial and moderate for HBV DNA levels ranged from 2000 to 20 000 IU/mL when compared with Abbott and Roche, respectively. The assay's performance was consistent across genotypes A, B, C, D, and E. DISCUSSION: This field evaluation showed that our HBV PCR test is a valuable alternative to proprietary PCR systems. PCR assays on open platforms contribute to expanding clinical laboratory solutions for diagnosing individuals who meet the viral load criteria for antiviral therapy (>20 000 IU/mL) and mother-to-child prophylaxis (>200 000 IU/mL).
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ADN Viral , Virus de la Hepatitis B , Hepatitis B , Humanos , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/aislamiento & purificación , ADN Viral/genética , África , Hepatitis B/diagnóstico , Hepatitis B/virología , Asia , Sensibilidad y Especificidad , Técnicas de Diagnóstico Molecular/métodos , Femenino , Carga Viral/métodos , Masculino , Reacción en Cadena de la Polimerasa/métodos , Adulto , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Persona de Mediana EdadRESUMEN
Hepatitis C virus (HCV) protease inhibitor resistance-associated substitutions are selected during triple-therapy breakthrough. This multicenter quality control study evaluated the expertise of 23 French laboratories in HCV protease inhibitor resistance genotyping. A panel of 12 well-defined blinded samples comprising two wild-type HCV strains, nine transcripts from synthetic NS3 mutant samples or from clinical strains, and one HCV RNA-negative sample was provided to the participating laboratories. The results showed that any laboratory with expertise in sequencing techniques should be able to provide reliable HCV protease inhibitor resistance genotyping. Only a 0.7% error rate was reported for the amino acid sites studied. The accuracy of substitution identification ranged from 75% to 100%, depending on the laboratory. Incorrect results were mainly related to the methodology used. The results could be improved by changing the primers and modifying the process in order to avoid cross-contamination. This study underlines the value of quality control programs for viral resistance genotyping, which is required prior to launching observational collaborative multicenter studies on HCV resistance to direct-acting antiviral agents.
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Antivirales/farmacología , Farmacorresistencia Viral/genética , Hepacivirus/efectos de los fármacos , Hepacivirus/genética , Inhibidores de Proteasas/farmacología , Proteínas no Estructurales Virales/genética , Secuencia de Aminoácidos , Antivirales/química , Secuencia de Bases , Genotipo , Hepacivirus/enzimología , Mutación , Inhibidores de Proteasas/química , Control de Calidad , Análisis de Secuencia de ADNRESUMEN
In 2022, the World Health Organization (WHO) estimated that hepatitis B virus (HBV) infections caused 1.5 million deaths, mostly attributable to complications from chronic infections, cirrhosis and hepatocellular carcinoma (HCC). Despite the availability of a vaccine, 296 million people were chronically infected in 2019. Asia and Africa are the continents most affected by this infection, with around 100 million people infected in Africa as a whole.Hepatitis Delta or D virus (HDV), which is a "satellite" virus of HBV, is often misunderstood and its diagnosis remains neglected. However, it is associated with acute fulminant forms and chronic forms of hepatitis leading to a more rapid evolution towards cirrhosis and HCC than during HBV mono-infection. Research on these two viruses HBV and HDV has progressed a lot in recent years, and new treatments are currently in development.In people living with the human immunodeficiency virus (PlHIV), liver disease is a major cause of morbidity and mortality. Due to common modes of transmission, dual or triple HIV/HBV or HIV/HBV/HDV infections are relatively common, particularly in HBV endemic regions such as Africa. However, while today most co-infected patients benefit from effective treatment against both HIV and HBV, the latter is not active against HDV. In Africa, hepatitis B and D have already been the subject of several studies. However, the frequency and clinical consequences of these co-infections have been little studied in the general population and in PlHIV.This review seeks to update the epidemiological and clinical data and the therapeutic perspectives of HDV co-infections or triple infections (HIV-HBV-HDV) in Africa.
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Carcinoma Hepatocelular , Coinfección , Infecciones por VIH , Hepatitis B , Hepatitis D , Neoplasias Hepáticas , Humanos , Coinfección/epidemiología , África/epidemiología , Hepatitis B/epidemiología , Virus de la Hepatitis B , Cirrosis Hepática , Virus de la Hepatitis Delta , Infecciones por VIH/complicaciones , Hepatitis D/diagnósticoRESUMEN
No recent data are available on hepatitis B virus (HBV) and hepatitis Delta virus (HDV) prevalence in Mauritania. One thousand twenty pregnant women and 946 patients visiting for routine checkups were screened for HBV and HDV infection. Demographic, epidemiological, ethnic, clinical, and biological data were recorded. HBV and HDV genotypes were determined by sequencing and phylogenetic analyses. In the pregnant women and patients cohorts, respectively, the prevalence of HBsAg (10.7% and 18.3%) and anti-HBcAb (66.3% and 76.5%) indicated high HBV endemicity. In pregnant women, exposure to HBV was significantly associated in multivariate analysis with education level, ethnicity, blood transfusion, and occupation. HDV antibodies (HDVAb) were found in 14.7% of pregnant women. In patients, HBsAg was found less frequently in females than in males. Again in multivariate analysis, exposure to HBV was significantly correlated with gender (males), and HDVAb positivity with age and gender. The HBV DNA viral load was >3 log IU/ml in only 10.1% of pregnant women and in 17.3% of patients. HDV-RNA was detectable in 21 (67.7%) of the 31 patients positive for HDVAb, and in 11 of the 16 pregnant women positive for HDVAb (68.8%). The most frequent HBV genotypes were: HBV/D, 53%; HBV/E, 35%; and HBV/A, 12%. Sub-genotyping revealed HBV/D1,/D7, and the recently described/D8. HDV genotypes were: HDV-1, 90.3% and HDV-5, 9.7%. This study confirms the high prevalence of HBV and HDV infections in Mauritania and demonstrates the high genetic diversity of HBV in this country.
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Virus de la Hepatitis B/genética , Hepatitis B/epidemiología , Hepatitis D/epidemiología , Virus de la Hepatitis Delta/genética , Complicaciones Infecciosas del Embarazo/epidemiología , Adolescente , Adulto , Anciano , Femenino , Genotipo , Hepatitis B/etnología , Hepatitis B/virología , Virus de la Hepatitis B/clasificación , Hepatitis D/etnología , Hepatitis D/virología , Virus de la Hepatitis Delta/clasificación , Humanos , Masculino , Mauritania/epidemiología , Persona de Mediana Edad , Epidemiología Molecular , Embarazo , Complicaciones Infecciosas del Embarazo/etnología , Complicaciones Infecciosas del Embarazo/virología , Prevalencia , Factores de Riesgo , Adulto JovenRESUMEN
The A1762T/G1764A double mutant in the basal core promoter (BCP) region of the hepatitis B virus (HBV) is associated with severe hepatic lesions while the G1899A mutation with the double mutant is associated with a significant reduction in the risk of severe fibrosis. This study aims to measure a number of markers in the serum of patients with chronic HBV infection and to assess relationships between these markers and BCP/precore mutants with consideration of the stage of fibrosis. The serum levels of resistin, TGF-ß1, MMP-1, TIMP-1, collagen IA1 and PDGF-BB, which are markers that are known to be involved in the process of hepatic fibrosis, were assayed. The serum levels of PDGF-BB and TIMP-1, and the mutation profile were independently associated with advanced fibrosis. A higher level of TIMP-1 was associated with advanced fibrosis regardless of the mutation status, and a higher level of PDGF-BB was associated with nonsevere fibrosis in patients infected with viruses harboring the A1762T/G1764A or A1762T/G1764A/G1899A mutations. Our results suggest an impact of the A1762T/G1764A mutant on the biological pathway related to TGF-ß1 and PDGF-BB. In vitro studies are needed to understand the impact of these mutants on the serum secretion of markers involved in fibrosis severity.
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Hepatitis B Crónica , Hepatitis B , Becaplermina/genética , Biomarcadores , ADN Viral/genética , Genotipo , Virus de la Hepatitis B/genética , Hepatitis B Crónica/complicaciones , Humanos , Cirrosis Hepática/complicaciones , Mutación , Inhibidor Tisular de Metaloproteinasa-1/genética , Factor de Crecimiento Transformador beta1/genéticaRESUMEN
BACKGROUND: In sub-Saharan Africa, administration of hepatitis B virus (HBV) birth-dose vaccines remains suboptimal. Evidence is scarce on whether African countries should focus on increasing vaccine coverage or developing strategies incorporating additional measures, such as peripartum antiviral prophylaxis to pregnant women at high risk. To better inform decision makers, we estimated the residual risk of mother-to-child transmission despite HBV birth-dose vaccine in Cameroon. METHODS: We did a single-centre, longitudinal observational study. Pregnant women were systematically screened for HBV surface antigen (HBsAg) at Tokombéré District Hospital (Tokombéré district, Cameroon). Children born to HBsAg-positive mothers in 2009-16 who received the HBV birth-dose vaccine and three subsequent doses of pentavalent vaccine at 6, 10, and 14 weeks were followed up prospectively in 2015-17. In children, capillary blood was obtained for HBsAg rapid test and dried blood spots to quantify HBV DNA concentrations. Venous blood was also collected from HBsAg-positive children. Mother-to-child transmission was confirmed by whole-genome sequencing. FINDINGS: Between Jan 31, 2009, and Dec 31, 2016, 22 243 (66·8%) of 33 309 pregnant women accepted antenatal HBV screening, of whom 3901 (17·5%) were HBsAg positive. 2004 (51·4%) of 3901 children who were born to HBsAg-positive mothers received the HBV birth-dose vaccine, of whom 1800 (89·8%) also completed the three-dose pentavalent vaccine. In total, the current analysis included 607 children who had a follow-up serosurvey. The prevalence of HBsAg was 5·6% in children who received the birth-dose vaccine in less than 24 h, 7·0% in those who received it 24-47 h after birth, and 16·7% in those who received it 48-96 h after birth (ptrend=0·083). 35 (89·7%) of 39 infected children were born to mothers positive for HBV e antigen with high HBV DNA of 5·3 log10 IU/mL or more. Whole-genome sequencing of HBV in infected mother-child pairs confirmed high identity proportions of 99·97-100%. INTERPRETATION: We documented a substantial risk of mother-to-child transmission despite timely administration of the HBV birth-dose vaccine within 24 h after birth. To reach WHO's elimination targets, peripartum antiviral prophylaxis might be required in parts of Africa, in addition to increasing coverage of the HBV birth-dose vaccine. FUNDING: Agence nationale de recherches sur le sida et les hépatites virales (ANRS).
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Hepatitis B , Complicaciones Infecciosas del Embarazo , Antivirales/uso terapéutico , Camerún/epidemiología , ADN Viral , Femenino , Hepatitis B/tratamiento farmacológico , Hepatitis B/epidemiología , Hepatitis B/prevención & control , Antígenos de Superficie de la Hepatitis B , Vacunas contra Hepatitis B , Virus de la Hepatitis B , Humanos , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Embarazo , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Complicaciones Infecciosas del Embarazo/epidemiología , Complicaciones Infecciosas del Embarazo/prevención & control , Vacunación , Vacunas Combinadas/uso terapéuticoRESUMEN
Since hepatitis B virus (HBV) replication involves an error-prone reverse transcription step, the rate of nucleotide changes during replication is higher than that found in other DNA viruses. As a result, HBV has a "quasispecies" distribution in infected individuals. Such selection processes to allow the emergence of variant viruses, such as precore (PC) and basal core promoter (BCP) mutants. The dominant PC variant is a point mutation of G to A at nucleotide 1896 (G1896A) that produces a premature stop codon, which terminates translation of the precore protein, resulting in the lack of HBe-antigen synthesis. BCP variants at nucleotides 1762 (A1762T) and 1764 (G1764A) likewise impair the production of HBeAg but at the transcriptional rather than the translational level. The impact of mutations in the precore and basal core promoter regions of the HBV virus on the course of chronic liver disease is not well established.
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OBJECTIVES: Hepatitis B and D infections are highly endemic in Mauritania, with prevalences ranging from 10 to 20%. With the present prospective transversal pilot study, we aimed to evaluate the prevalences of HBV, HCV, and HDV infections in healthcare workers (HCWs), and offer treatment or vaccination as required. METHODS: At inclusion, each HCW was screened for anti-HBc Ab (followed by HBsAg assay when positive). Additional biological analyses were performed for HBsAg + cases. Depending on the results, HBV vaccination or anti-viral treatment was offered. RESULTS: A total of 3,857 HCWs were included, of whom 1,363 tested negative for anti-HBc Ab and received full vaccination. Of the 2,494 HCWs who were positive for anti-HBc Ab, 1,246 were positive for anti-HBs Ab and 418 were positive for HBsAg. Three HCWs were positive for HBeAg; 66 and 18 had HBV DNA levels respectively > 2,000 and > 20,000 IU/mL; and 48 were positive for anti-HDV Ab among whom 10 were positive for HDV RNA. HCV prevalence was 0.5%. Only seven HCWs fulfilled the criteria for treatment and five of them were treated. CONCLUSION: Few HCWs in Mauritania are immunised against HBV. The prevalences of anti-HBc Ab and HBsAg observed in this work were similar to those observed in our earlier works, whereas prevalence of active HDV infection was less high. HBV and HDV infections are a serious health concern in Mauritania. New recommendations developed in accordance with WHO guidelines should include mandatory HBV screening and immunisation for HCWs.
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Virus de la Hepatitis B , Hepatitis B , Personal de Salud , Hepatitis B/epidemiología , Hepatitis B/prevención & control , Anticuerpos contra la Hepatitis B , Antígenos de Superficie de la Hepatitis B , Humanos , Mauritania , Proyectos Piloto , Estudios Prospectivos , VacunaciónRESUMEN
BACKGROUND: Prevention of mother-to-child transmission (MTCT) of hepatitis B virus (HBV) involves neonatal immunoprophylaxis, with a birth dose of hepatitis B vaccine and immune globulin, and provision of peripartum antiviral prophylaxis in highly viraemic women. However, access to assays to quantify HBV DNA levels remains inadequate in resource-poor settings. This study was commissioned by WHO and aimed to identify the HBV DNA threshold for MTCT, to assess the sensitivity and specificity of hepatitis B e antigen (HBeAg) testing to identify pregnant women with HBV DNA levels above this threshold, and to predict MTCT of HBV infection on the basis of HBeAg testing. METHODS: For this systematic review and meta-analysis, we searched the PubMed, EMBASE, Scopus, CENTRAL, CNKI, and Wanfang databases for studies of pregnant women with chronic HBV infection without concurrent antiviral therapy, published between Jan 1, 2000, and April 3, 2019. Studies were eligible for inclusion if MTCT in mother-child pairs could be stratified by different levels of maternal HBV DNA during pregnancy, if maternal HBeAg status could be stratified by HBV DNA level, and if the MTCT status of infants could be stratified by maternal HBeAg status during pregnancy. Studies that selected pregnant women on the basis of HBeAg serostatus or HBV DNA levels were excluded. Aggregate data were extracted from eligible studies by use of a pre-piloted form; study authors were contacted to clarify any uncertainties about potential duplication or if crucial information was missing. To pool sensitivities and specificities of maternal HBeAg to identify highly viraemic women and to predict MTCT events, we used the DerSimonian-Laird bivariate random effects model. This study is registered with PROSPERO, CRD42019138227. FINDINGS: Of 9007 articles identified, 67 articles (comprising 66 studies) met the inclusion criteria. The risk of MTCT despite infant immunoprophylaxis was negligible (0·04%, 95% CI 0·00-0·25) below a maternal HBV DNA level of 5·30 log10 IU/mL (200â000 IU/mL) and increased above this threshold. The pooled sensitivity of HBeAg testing to identify HBV DNA levels of 5·30 log10 IU/mL or greater in pregnant women was 88·2% (83·9-91·5) and pooled specificity was 92·6% (90·0-94·5). The pooled sensitivity of HBeAg testing in predicting MTCT of HBV infection despite infant immunoprophylaxis was 99·5% (95% CI 91·7-100) and pooled specificity was 62·2% (55·2-68·7). INTERPRETATION: Maternal HBV DNA of 5·30 log10 IU/mL or greater appears to be the optimal threshold for MTCT of HBV infection despite infant immunoprophylaxis. HBeAg is accurate to identify women with HBV DNA levels above this threshold and has high sensitivity to predict cases of immunoprophylaxis failure. In areas where HBV DNA assays are unavailable, HBeAg can be used as an alternative to assess eligibility for antiviral prophylaxis. FUNDING: World Health Organization.
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Antivirales/uso terapéutico , Vacunas contra Hepatitis B/uso terapéutico , Antígenos e de la Hepatitis B/uso terapéutico , Hepatitis B Crónica/tratamiento farmacológico , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Complicaciones Infecciosas del Embarazo/prevención & control , Adulto , Femenino , Humanos , EmbarazoRESUMEN
BACKGROUND: Accurate detection of Hepatitis B Surface Antigen (HBsAg) is an important aid in the diagnosis of patients infected with the hepatitis B virus (HBV). A multi-center study was conducted to characterize the performance of the HBsAg assay on the family of Access immunoassay systems from Beckman Coulter. METHODS: The Access HBsAg assay was characterized in a multi-center study and compared to the Abbott AxSYM* and PRISM* HBsAg assays. The bioMérieux VIDAS* assay was used to resolve discrepant results. Reproducibility studies (intra-assay, inter-assay and inter-lot) were performed with pooled serum samples (negative sample, close to cut off, low, medium and high positive samples). Analytical sensitivity, subtype and genotype detection were studied with various commercial panels (SFTS panel, WHO 80/549, WHO 00/588, Teragenix HBV Genotype panel). A panel of recombinant HBsAg mutant proteins was tested to investigate reactivity towards genetic mutations. Clinical sensitivity was verified with seroconversion panels and samples from subjects with known HBV infection. Analytical specificity was studied with samples from patients with potential cross-reactive infections. Clinical specificity was validated among blood donors and a hospitalized population. RESULTS: The imprecision was < 10%. Analytical sensitivity was < or = 0.1 ng/mL (SFTS panel), 0.020 PEI Units/mL (ad panel), 0.024 PEI Units/mL (ay panel), 0.092 IU/mL with WHO 80/549 and 0.056 IU/mL with WHO 00/588. All genotype samples and HBsAg mutants were reactive with the Access HBsAg assay. Seroconversion panels tested showed no significant difference with the reference method. Sensitivity for subjects with known HBV infection was 100%. No interference with potentially cross-reactive infections was observed after confirmatory testing. Specificity was 99.96% (100% after confirmatory testing) in a blood donor population and 99.5% (100% after confirmatory testing) in a hospitalized population. Excellent separation of positive and negative populations was observed. CONCLUSIONS: The Access HBsAg and HBsAg Confirmatory assays meet all clinical and analytical performance requirements of assays for the detection of HBsAg.
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Antígenos de Superficie de la Hepatitis B/sangre , Hepatitis B/diagnóstico , Inmunoensayo/métodos , Autoanálisis , Donantes de Sangre , Reacciones Cruzadas , ADN Viral/análisis , Hepatitis B/sangre , Hospitales , Humanos , Proteínas Recombinantes/análisis , Valores de Referencia , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Pruebas SerológicasRESUMEN
OBJECTIVES: In France, cervical cancer screening is based on human papillomavirus (HPV) testing on cervical samples (women aged 30-65) and cytological examination of Pap smears (25-29), but screening coverage is unsatisfactory. The CapU3 study aimed to propose urinary HPV testing on 13,535 women aged 35 to 65 who had not had a Pap smear since 2010. METHODS: High-risk HPV (HR-HPV) detection was performed using a real-time PCR (Anyplex II HPV 28 Detection, Seegene®). Women with HR-HPV positive results were encouraged to have a cervical smear as soon as possible to detect the presence of cervical lesions. RESULTS: The participation rate was 15.4%. Out of the 1,915 analyzed specimens, 1,711 and 190 were negative and positive, respectively, for at least 1 HR-HPV genotype. HR-HPV genotypes other than HPV-16 or HPV-18 were mostly detected as HPV-53 (23.7%) and HPV-68 (14.2%). A satisfactory gynecological follow-up was observed for HPV-positive women (92.1%). 23 abnormal smears were observed and eight high-grade cytological lesions after colposcopy and biopsy were diagnosed. CONCLUSIONS: As home HPV urinary testing is non-invasive and does not require medical attention, this method may be an alternative for women who are reluctant to have a Pap smear and thus extend screening coverage.
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Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Adulto , Anciano , ADN Viral/genética , Detección Precoz del Cáncer , Femenino , Francia/epidemiología , Humanos , Persona de Mediana Edad , Prueba de Papanicolaou , Papillomaviridae/genética , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/epidemiología , Embarazo , Sensibilidad y Especificidad , Neoplasias del Cuello Uterino/diagnóstico , Frotis VaginalRESUMEN
BACKGROUND: The detection and quantification of hepatitis B virus (HBV) DNA from dried blood spots (DBS) is a major tool for chronic hepatitis B management in resource-limited settings. This strategy fits in perfectly with the hepatitis control plan promoted by the World Health Organization. However, few commercial methods are validated for viral load (VL) measurement on DBS. OBJECTIVES: Our objective was to evaluate the performance of the HBV VL measurement of the Aptima™ HBV Quant Dx assay on DBS compared to plasma samples on the Panther® platform (Hologic). STUDY DESIGN: 266 whole blood samples for routine measurement were included. Five spots of 75⯵L of whole blood were loaded onto a card before centrifugation and plasma settling. RESULTS: 149 samples were quantifiable and 117 were not detected. We achieved excellent linearity (r²â¯=â¯0.994) over a wide range of measurements suitable for clinical practice, and a 95 % lower limit of detection (LLOD-95 %) at 2.65 log10 IU/mL (445 IU/mL). A good performance of this assay was observed for samples with HBV VLâ¯>â¯LLOD-95 % and 100 % of samples were detected if HBV VL was above 2.95 log10 IU/mL. The correlation between the two matrices for quantitative VLs was good (r²â¯=â¯0.978) with a very low bias (-0.002 log10 IU/mL). CONCLUSION: The Aptima™ assay can properly detect and quantify HBV DNA in DBS, providing a satisfactory use in clinical monitoring and therapeutic decisions. DBS represents an excellent alternative to plasma, especially in resource-limited countries, while maintaining the performance and advantages of an automated technique.