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A novel quantitative microarray antibody capture assay identifies an extremely high hepatitis delta virus prevalence among hepatitis B virus–infected mongolians

Xiaohua ChenDepartment of Medicine, Division of Gastroenterology and Hepatology,Stanford University School of Medicine,Palo Alto,CAOdgerel OidovsambuuLiver Center,Ulaanbaatar,MongoliaPing LiuDepartment of Medicine, Division of Gastroenterology and Hepatology,Stanford University School of Medicine,Palo Alto,CARosslyn GroselyDepartment of Medicine, Division of Gastroenterology and Hepatology,Stanford University School of Medicine,Palo Alto,CAMenashe ElazarDepartment of Medicine, Division of Gastroenterology and Hepatology,Stanford University School of Medicine,Palo Alto,CAVirginia D. WinnDepartment of Obstetrics and Gynecology,Stanford University,Palo Alto,CABenjamin FramDepartment of Medicine, Division of Gastroenterology and Hepatology,Stanford University School of Medicine,Palo Alto,CAZhang BoaDepartment of Chemistry,Stanford University,Palo Alto,CAHongjie DaiDepartment of Chemistry,Stanford University,Palo Alto,CABekhbold DashtserenLiver Center,Ulaanbaatar,MongoliaDahgwahdorj YagaanbuyantLiver Center,Ulaanbaatar,MongoliaZulkhuu GendenNaranbaatar DashdorjAndreas BungertNaranjargal DashdorjJeffrey S. GlennDepartment of Medicine, Division of Gastroenterology and Hepatology,Stanford University School of Medicine,Palo Alto,CA
2016en
ABI

Аннотация

Hepatitis delta virus (HDV) causes the most severe form of human viral hepatitis. HDV requires a hepatitis B virus (HBV) coinfection to provide HDV with HBV surface antigen envelope proteins. The net effect of HDV is to make the underlying HBV disease worse, including higher rates of hepatocellular carcinoma. Accurate assessments of current HDV prevalence have been hampered by the lack of readily available and reliable quantitative assays, combined with the absence of a Food and Drug Administration–approved therapy. We sought to develop a convenient assay for accurately screening populations and to use this assay to determine HDV prevalence in a population with abnormally high rates of hepatocellular carcinoma. We developed a high‐throughput quantitative microarray antibody capture assay for anti‐HDV immunoglobulin G wherein recombinant HDV delta antigen is printed by microarray on slides coated with a noncontinuous, nanostructured plasmonic gold film, enabling quantitative fluorescent detection of anti‐HDV antibody in small aliquots of patient serum. This assay was then used to screen all HBV‐infected patients identified in a large randomly selected cohort designed to represent the Mongolian population. We identified two quantitative thresholds of captured antibody that were 100% predictive of the sample either being positive on standard western blot or harboring HDV RNA detectable by real‐time quantitative PCR. Subsequent screening of the HBV + cohort revealed that a remarkable 57% were RNA + and an additional 4% were positive on western blot alone. Conclusion: The quantitative microarray antibody capture assay's unique performance characteristics make it ideal for population screening; its application to the Mongolian HBV surface antigen–positive population reveals an apparent ∼60% prevalence of HDV coinfection among these HBV‐infected Mongolian subjects, which may help explain the extraordinarily high rate of hepatocellular carcinoma in Mongolia. (H epatology 2017;66:1739–1749)

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