title: A novel quantitative microarray antibody capture assay identifies an extremely high hepatitis delta virus prevalence among hepatitis B virus-infected mongolians.
abstract: 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.
  
  
  
  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. (Hepatology 2017;66:1739-1749).
authors.affiliation: Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, CA.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Chen
authors.affiliation: Liver Center, Ulaanbaatar, Mongolia.|Mongolian National University, Ulaanbaatar, Mongolia.
authors.forename: Odgerel
authors.initials: O
authors.lastname: Oidovsambuu
authors.affiliation: Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, CA.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, CA.
authors.forename: Rosslyn
authors.initials: R
authors.lastname: Grosely
authors.affiliation: Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, CA.
authors.forename: Menashe
authors.initials: M
authors.lastname: Elazar
authors.affiliation: Department of Obstetrics and Gynecology, Stanford University, Palo Alto, CA.
authors.forename: Virginia D
authors.initials: VD
authors.lastname: Winn
authors.affiliation: Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, CA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Fram
authors.affiliation: Department of Chemistry, Stanford University, Palo Alto, CA.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Boa
authors.affiliation: Department of Chemistry, Stanford University, Palo Alto, CA.
authors.forename: Hongjie
authors.initials: H
authors.lastname: Dai
authors.affiliation: Liver Center, Ulaanbaatar, Mongolia.|Onom Foundation, Ulaanbaatar, Mongolia.|Mongolian National University of Health Sciences, Ulaanbaatar, Mongolia.
authors.forename: Bekhbold
authors.initials: B
authors.lastname: Dashtseren
authors.affiliation: Liver Center, Ulaanbaatar, Mongolia.|Onom Foundation, Ulaanbaatar, Mongolia.|Mongolian National University of Health Sciences, Ulaanbaatar, Mongolia.
authors.forename: Dahgwahdorj
authors.initials: D
authors.lastname: Yagaanbuyant
authors.affiliation: Liver Center, Ulaanbaatar, Mongolia.|Onom Foundation, Ulaanbaatar, Mongolia.
authors.forename: Zulkhuu
authors.initials: Z
authors.lastname: Genden
authors.affiliation: Onom Foundation, Ulaanbaatar, Mongolia.
authors.forename: Naranbaatar
authors.initials: N
authors.lastname: Dashdorj
authors.affiliation: Onom Foundation, Ulaanbaatar, Mongolia.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bungert
authors.affiliation: Liver Center, Ulaanbaatar, Mongolia.|Onom Foundation, Ulaanbaatar, Mongolia.
authors.forename: Naranjargal
authors.initials: N
authors.lastname: Dashdorj
authors.affiliation: Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, CA.|Department of Microbiology and Immunology, Stanford University School of Medicine, Palo Alto, CA.|Veterans Administration Medical Center, Palo Alto, CA.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Glenn
mesh_terms: D000914:Antibodies, Viral / Q000032:analysis*; D015153:Blotting, Western; D016022:Case-Control Studies; D060085:Coinfection; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006509:Hepatitis B / Q000150:complications / Q000453:epidemiology*; D003699:Hepatitis D / Q000150:complications / Q000175:diagnosis / Q000453:epidemiology*; D003698:Hepatitis Delta Virus / Q000302:isolation & purification*; D006801:Humans; D046228:Microarray Analysis / Q000295:instrumentation / Q000379:methods*; D008986:Mongolia / Q000453:epidemiology; D011247:Pregnancy; D015995:Prevalence; D012680:Sensitivity and Specificity
chemical_list: D000914:Antibodies, Viral