{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T09:03:16Z","timestamp":1762160596987,"version":"3.28.0"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":9405,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1989,12]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>The intrahepatic distribution of hepatitis delta virus RNA was studied by <jats:italic toggle=\"yes\">in situ<\/jats:italic> hybridization in 33 formalin\u2013fixed, paraffin\u2013embedded biopsies from 17 chronic hepatitis B virus carriers superinfected with hepatitis delta virus. The findings were correlated with the expression of the hepatitis delta antigen, the duration of the hepatitis delta virus infection and the eosinophilic degeneration of the hepatocytes. Intranuclear hepatitis delta virus RNA and antigen were found in 28 specimens, whereas the remaining five were negative for both markers. Hepatitis delta virus RNA and antigen were mostly found within the same cell. In 20 specimens, however, a variable number of hepatocytes showed the presence of hepatitis delta virus RNA alone. The percentage of these over the total number of infected cells was higher in the specimens taken within 1 year from the acute delta hepatitis, whereas their absence was invariably associated with a long\u2013established hepatitis delta virus infection. Interestingly, the vast majority of hepatocytes undergoing eosinophilic degeneration, a change significantly associated with hepatitis delta virus infection, did not show the presence of either hepatitis delta virus RNA or the viral antigen, suggesting a lack of association, at the cellular level, between viral replication and cytopathological change. The specificity of the detection of hepatitis delta virus RNA was confirmed by negative findings in nine specimens from seven chronic hepatitis B virus carriers without evidence of past or current hepatitis delta virus infection. The loss in sensitivity due to the formalin fixation was estimated to be 50% of that obtained in frozen biopsies, as determined by counting autoradiographic grains over infected cells. Consistent results were obtained when sections from the same biopsies were hybridized in separate experiments. Detection of hepatitis delta virus RNA by <jats:italic toggle=\"yes\">in situ<\/jats:italic> hybridization in formalin\u2013fixed, paraffin\u2013embedded sections is therefore a rapid, specific, sensitive and reproducible assay for monitoring intrahepatic hepatitis delta virus replication and might have diagnostic relevance.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.1840100604","type":"journal-article","created":{"date-parts":[[2007,3,3]],"date-time":"2007-03-03T22:42:59Z","timestamp":1172961779000},"page":"916-920","update-policy":"http:\/\/dx.doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":26,"title":["Intrahepatic Markers of Hepatitis Delta Virus Infection: A Study By In Situ Hybridization"],"prefix":"10.1097","volume":"10","author":[{"given":"Francesco","family":"Negro","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ferruccio","family":"Bonino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrian Di","family":"Bisceglie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jay H.","family":"Hoofnagle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John L.","family":"Gerin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"10.1002\/hep.1840100604-BIB1","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/S0168-8278(85)80766-2","volume":"1","author":"Rizzetto","year":"1985","journal-title":"J Hepatol"},{"key":"10.1002\/hep.1840100604-BIB2","doi-asserted-by":"crossref","first-page":"6124","DOI":"10.1073\/pnas.77.10.6124","volume":"77","author":"Rizzetto","year":"1980","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1002\/hep.1840100604-BIB3","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1038\/323558a0","volume":"323","author":"Kos","year":"1986","journal-title":"Nature"},{"key":"10.1002\/hep.1840100604-BIB4","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1038\/323508a0","volume":"323","author":"Wang","year":"1986","journal-title":"Nature"},{"key":"10.1002\/hep.1840100604-BIB5","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/329343a0","volume":"329","author":"Makino","year":"1987","journal-title":"Nature"},{"key":"10.1002\/hep.1840100604-BIB6","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1128\/JVI.62.6.1855-1861.1988","volume":"62","author":"Kuo","year":"1988","journal-title":"J Virol"},{"key":"10.1002\/hep.1840100604-BIB7","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1002\/hep.1840060612","volume":"6","author":"Smedile","year":"1986","journal-title":"Hepatology"},{"key":"10.1002\/hep.1840100604-BIB8","first-page":"591","volume-title":"Hepadnaviruses","author":"Gowans","year":"1987","unstructured":", , et al. Molecular markers of WHV and HDV in single cells. In: , , eds. Hepadnaviruses. New York: Alan R. Liss, 1987; 591\u2013600."},{"key":"10.1002\/hep.1840100604-BIB9","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1093\/infdis\/158.1.151","volume":"158","author":"Negro","year":"1988","journal-title":"J Infect Dis"},{"key":"10.1002\/hep.1840100604-BIB10","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/0042-6822(88)90078-5","volume":"167","author":"Gowans","year":"1988","journal-title":"Virology"},{"key":"10.1002\/hep.1840100604-BIB11","first-page":"s48","volume":"5","author":"Negro","year":"1987","journal-title":"J Hepatol"},{"key":"10.1002\/hep.1840100604-BIB12","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/S0168-8278(88)80457-4","volume":"6","author":"Negro","year":"1988","journal-title":"J Hepatol"},{"key":"10.1002\/hep.1840100604-BIB13","first-page":"169","volume-title":"Viral hepatitis and delta infection","author":"Verme","year":"1983","unstructured":", , et al. Histopathology of chronic delta hepatitis. In: , , eds. Viral hepatitis and delta infection. New York: Alan R. Liss, 1983: 169\u2013176."},{"key":"10.1002\/hep.1840100604-BIB14","first-page":"397","volume-title":"Viral hepatitis and delta infection","author":"Popper","year":"1983","unstructured":"Concerning particularly delta agent infection, chronic hepatitis, and relation of hepatitis B infection to hepatocellular carcinoma. In: , , eds. Viral hepatitis and delta infection. New York: Alan R. Liss, 1983: 397\u2013410."},{"key":"10.1002\/hep.1840100604-BIB15","first-page":"145","volume-title":"The hepatitis delta virus and its infection","author":"Bonino","year":"1987","unstructured":", , et al. The natural history of chronic delta hepatitis. In: , , eds. The hepatitis delta virus and its infection. New York: Alan R. Liss, 1987: 145\u2013152."},{"key":"10.1002\/hep.1840100604-BIB16","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1128\/JCM.14.2.173-177.1981","volume":"14","author":"Crivelli","year":"1981","journal-title":"J Clin Microbiol"},{"key":"10.1002\/hep.1840100604-BIB17","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/S0140-6736(84)90703-7","volume":"2","author":"Blum","year":"1984","journal-title":"Lancet"},{"key":"10.1002\/hep.1840100604-BIB18","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1002\/jmv.1890150407","volume":"15","author":"Negro","year":"1985","journal-title":"J Med Virol"},{"key":"10.1002\/hep.1840100604-BIB19","first-page":"411","volume":"120","author":"Rijntijes","year":"1985","journal-title":"Am J Pathol"},{"key":"10.1002\/hep.1840100604-BIB20","first-page":"475","volume":"55","author":"Brambilla","year":"1986","journal-title":"Lab Invest"},{"key":"10.1002\/hep.1840100604-BIB21","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/0166-0934(88)90127-9","volume":"20","author":"Cubie","year":"1988","journal-title":"J Virol Methods"},{"key":"10.1002\/hep.1840100604-BIB22","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/S0046-8177(84)80076-3","volume":"15","author":"Myerson","year":"1984","journal-title":"Hum Pathol"},{"key":"10.1002\/hep.1840100604-BIB23","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1007\/BF00710763","volume":"409","author":"Loening","year":"1986","journal-title":"Virchows Arch A Pathol Anat"},{"key":"10.1002\/hep.1840100604-BIB24","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/BF02896564","volume":"55","author":"Borisch","year":"1988","journal-title":"Virchows Arch B Cell Pathol"},{"key":"10.1002\/hep.1840100604-BIB25","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1097\/00000478-198805000-00004","volume":"12","author":"Masih","year":"1988","journal-title":"Am J Surg Pathol"},{"key":"10.1002\/hep.1840100604-BIB26","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1016\/S0140-6736(88)92180-0","volume":"1","author":"Naoumov","year":"1988","journal-title":"Lancet"},{"key":"10.1002\/hep.1840100604-BIB27","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/0042-6822(83)90460-9","volume":"126","author":"Brigati","year":"1983","journal-title":"Virology"},{"key":"10.1002\/hep.1840100604-BIB28","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/B978-0-12-470207-3.50013-9","volume":"7","author":"Haase","year":"1984","journal-title":"Methods Virol"},{"key":"10.1002\/hep.1840100604-BIB29","volume-title":"Techniques of autoradiography","author":"Rogers","year":"1979","unstructured":"Techniques of autoradiography. Amsterdam: Elsevier, 1979."},{"key":"10.1002\/hep.1840100604-BIB30","doi-asserted-by":"crossref","first-page":"8774","DOI":"10.1073\/pnas.83.22.8774","volume":"83","author":"Chen","year":"1986","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1002\/hep.1840100604-BIB31","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1002\/hep.1840060613","volume":"6","author":"Verme","year":"1986","journal-title":"Hepatology"},{"key":"10.1002\/hep.1840100604-BIB32","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1002\/hep.1840020509","volume":"2","author":"Dienes","year":"1982","journal-title":"Hepatology"},{"key":"10.1002\/hep.1840100604-BIB33","first-page":"181","volume-title":"The hepatitis delta virus and its infection","author":"Hadziyannis","year":"1987","unstructured":", , et al. Endemic hepatitis delta virus infection in a Greek community. In: , , eds. The hepatitis delta virus and its infection. New York: Alan R. 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