Abstract
Development of serological and nucleic acid testing (NAT) has revolutionized hepatitis C virus (HCV) diagnosis. Although third generation anti-HCV enzyme immunoassays (EIAs) are very effective for testing high prevalence populations, confirmatory testing is still necessary when these tests are applied to populations with a low HCV prevalence to exclude false positive results. Limitations of third generation anti-HCV EIAs include: the relatively prolonged time between acute infection and detection of seroconversion (which typically requires at least 5–6 weeks); delayed seroconversions in immunocompromised hosts (requiring months to years); and the inability of serological tests to confirm active HCV infection. In contrast, nucleic acid testing (NAT) can directly detect HCV RNA in serum, plasma or tissue and thereby confirm active infection as well as narrow the window between infection and HCV detection to as little as 1–2 weeks. Commercial NAT assays are now highly sensitive, specific, and reproducible and have largely replaced unreliable home brew nucleic acid amplification assays. Qualitative commercial NAT are typically more sensitive than quantitative assays and therefore the method of choice to confirm active infection. Given the efficacy of combination therapy with interferon/ribavirin and newer antiviral agents under development, HCV infection may become curable, which will likely impact future disease transmission. As the therapeutic costs are currently very high, there is clearly a need to assess the utility of quantitative NAT and to further evaluate the role of HCV genotyping to optimize antiviral therapy. Thus for the foreseeable future, a combination of both serological tests and NAT will be required for cost-effective HCV diagnosis and monitoring.
Electronic Supplementary Material
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Résumé
La mise au point de tests sérologiques et de tests d’acide nucléique (TAN) a révolutionné le diagnostic du virus de l’hépatite C (VHC). Même si les dosages immuno-enzymatiques (EIA) de troisième génération sont très efficaces comme tests dans des populations où la prévalence de la maladie est élevée, des tests de confirmation sont toujours nécessaires lorsque la prévalence du VHC est faible, pour exclure les faux résultats positifs. Les limites des EIA de troisième génération comprennent le délai relativement long entre le moment d’une infection aiguë et la détection de la séroconversion (en général au moins 5 à 6 semaines), le retard de la séroconversion (plusieurs mois ou des années) chez les sujets immunodéprimés et l’incapacité pour les tests sérologiques de confirmer le caractère actif d’une infection par le VHC. Par contre, les TAN permettent de détecter directement la présence d’ARN du VHC dans le sérum, le plasma ou des tissus, et donc de confirmer une infection active et de ramener à 1 ou 2 semaines le délai entre une infection et la détection du VHC. Les TAN disponibles sur le marché sont maintenant très sensibles, spécifiques et reproductibles et ont largement remplacé les tests par amplification d’acide nucléique, artisanaux et peu fiables. Parmi les TAN commerciaux, les tests qualitatifs sont généralement plus sensibles que les tests quantitatifs et constituent donc la méthode de choix pour confirmer une infection active. Étant donné l’efficacité de la bithérapie interféron–ribavirine et des nouveaux agents antivirus en cours de mise au point, l’hépatite C pourrait devenir curable, ce qui aura probablement des effets dans l’avenir sur la transmission de la maladie. Comme les coûts du traitement sont actuellement très élevés, il y a un besoin manifeste d’évaluer l’utilité de TAN quantitatifs et d’étudier plus à fond le rôle de la détermination du génotype du VHC afin d’optimiser le traitement. Par conséquent, dans un avenir prévisible, une combinaison de tests sérologiques et de TAN demeurera nécessaire pour un diagnostic et un suivi du VHC à un coût raisonnable.
French language version/Version en Français
Diagnostic et test du virus de l’hépatite C
Footnotes
Cet article a été traduit par Benoît Thouin de Tetracomm Inc.
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