Histologic, Viral, and Molecular Correlates of Dengue Fever Infection of the Liver Using Highly Sensitive Immunohistochemistry
The mechanism by which the virus associated with dengue fever can cause a fatal hepatitis is not well understood. The purpose of this study was to examine 9 cases of fatal dengue hemorrhagic fever-associated hepatitis, and to correlate the histologic findings with viral detection and cytokine respon...
Gespeichert in:
Veröffentlicht in: | Diagnostic molecular pathology 2006-12, Vol.15 (4), p.223-228 |
---|---|
Hauptverfasser: | , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 228 |
---|---|
container_issue | 4 |
container_start_page | 223 |
container_title | Diagnostic molecular pathology |
container_volume | 15 |
creator | Carvalho de Macedo, Fabiane Nicol, Alcina F Cooper, Lynn D Yearsley, Martha Cordovil Pires, Andrea Rodrigues Nuovo, Gerard J |
description | The mechanism by which the virus associated with dengue fever can cause a fatal hepatitis is not well understood. The purpose of this study was to examine 9 cases of fatal dengue hemorrhagic fever-associated hepatitis, and to correlate the histologic findings with viral detection and cytokine response. The histologic changes were nonspecific and included massive hepatic necrosis and a pauci-cellular acute hepatitis. Viral cDNA detection by reverse transcriptase in situ polymerase chain reaction demonstrated that the fatal hepatitis was due to infection on average of >90% of hepatocytes and many Kupffer cells. Similar results were obtained using immunohistochemistry for viral protein using an automated highly sensitive system. Immunohistochemical analysis for tumor necrosis factor α, and interleukin-2, showed rare positive Kupffer cells. In comparison, fatal cases of hepatitis C associated liver failure demonstrated far fewer infected hepatocytes and a concomitant strong up-regulation of many cytokines, notably tumor necrosis factor α and interleukin-2. It is concluded that fatal dengue hemorrhagic fever is associated with acute, severe liver damage due primarily to massive direct infection of hepatocytes and Kupffer cells with minimal cytokine response. The infection can be readily detected in a few hours using an automated system that has a sensitivity equivalent to reverse transcriptase in situ polymerase chain reaction. |
doi_str_mv | 10.1097/01.pdm.0000213462.60645.cd |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_68181255</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>68181255</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3625-3bd10cd61d7a80777e3719e16a9d0c795a1ae03406b859edb3a3e015a8925fc03</originalsourceid><addsrcrecordid>eNpFkEGP0zAQhSMEYpeFv4AsDpw2YSaOnYQbKiytVMQBlqvl2tMm4MTFTlj1wm_HoZXWB89o_M178suyNwgFQlu_AyyOdiggnRJ5JctCgqxEYeyT7BoF53kFUj5NPYgyb4XAq-xFjD8Tz6tGPM-usMaylAKus7_rPk7e-UNvbtmPPmh3y_Ro2RfvyMxOB7byIZDTE0Xm9-wjjYeZ2B39ocA2457M1PtxeZk6Ytt-Gd_HfjywdX_o3Il9ozH2U5qzzTDMo-8WP9PRkGo4vcye7bWL9OpSb7L7u0_fV-t8-_XzZvVhmxsuS5HznUUwVqKtdQN1XROvsSWUurVg6lZo1JQ-B3LXiJbsjmtOgEI3bSn2BvhN9vasewz-90xxUsnfkHN6JD9HJRtssBQige_PoAk-xkB7dQz9oMNJIaglfQWoUvrqMX31P31lbFp-fXGZdwPZx9VL3AmozsCDdxOF-MvNDxRUR9pN3SKJbRLLSwCJ6YJ8cRH8H1NYku8</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>68181255</pqid></control><display><type>article</type><title>Histologic, Viral, and Molecular Correlates of Dengue Fever Infection of the Liver Using Highly Sensitive Immunohistochemistry</title><source>MEDLINE</source><source>Journals@Ovid Complete</source><creator>Carvalho de Macedo, Fabiane ; Nicol, Alcina F ; Cooper, Lynn D ; Yearsley, Martha ; Cordovil Pires, Andrea Rodrigues ; Nuovo, Gerard J</creator><creatorcontrib>Carvalho de Macedo, Fabiane ; Nicol, Alcina F ; Cooper, Lynn D ; Yearsley, Martha ; Cordovil Pires, Andrea Rodrigues ; Nuovo, Gerard J</creatorcontrib><description>The mechanism by which the virus associated with dengue fever can cause a fatal hepatitis is not well understood. The purpose of this study was to examine 9 cases of fatal dengue hemorrhagic fever-associated hepatitis, and to correlate the histologic findings with viral detection and cytokine response. The histologic changes were nonspecific and included massive hepatic necrosis and a pauci-cellular acute hepatitis. Viral cDNA detection by reverse transcriptase in situ polymerase chain reaction demonstrated that the fatal hepatitis was due to infection on average of >90% of hepatocytes and many Kupffer cells. Similar results were obtained using immunohistochemistry for viral protein using an automated highly sensitive system. Immunohistochemical analysis for tumor necrosis factor α, and interleukin-2, showed rare positive Kupffer cells. In comparison, fatal cases of hepatitis C associated liver failure demonstrated far fewer infected hepatocytes and a concomitant strong up-regulation of many cytokines, notably tumor necrosis factor α and interleukin-2. It is concluded that fatal dengue hemorrhagic fever is associated with acute, severe liver damage due primarily to massive direct infection of hepatocytes and Kupffer cells with minimal cytokine response. The infection can be readily detected in a few hours using an automated system that has a sensitivity equivalent to reverse transcriptase in situ polymerase chain reaction.</description><identifier>ISSN: 1052-9551</identifier><identifier>EISSN: 1533-4066</identifier><identifier>DOI: 10.1097/01.pdm.0000213462.60645.cd</identifier><identifier>PMID: 17122650</identifier><language>eng</language><publisher>United States: Lippincott Williams & Wilkins, Inc</publisher><subject>Dengue Virus - genetics ; Dengue Virus - isolation & purification ; Hepatitis, Viral, Human - etiology ; Hepatitis, Viral, Human - metabolism ; Hepatitis, Viral, Human - pathology ; Hepatitis, Viral, Human - virology ; Humans ; Immunohistochemistry ; Interleukin-2 - analysis ; Liver - chemistry ; Liver - pathology ; Liver - virology ; Necrosis ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Viral - analysis ; Severe Dengue - complications ; Severe Dengue - metabolism ; Severe Dengue - pathology ; Severe Dengue - virology ; Tumor Necrosis Factor-alpha - analysis ; Viral Proteins - analysis</subject><ispartof>Diagnostic molecular pathology, 2006-12, Vol.15 (4), p.223-228</ispartof><rights>2006 Lippincott Williams & Wilkins, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3625-3bd10cd61d7a80777e3719e16a9d0c795a1ae03406b859edb3a3e015a8925fc03</citedby><cites>FETCH-LOGICAL-c3625-3bd10cd61d7a80777e3719e16a9d0c795a1ae03406b859edb3a3e015a8925fc03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17122650$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Carvalho de Macedo, Fabiane</creatorcontrib><creatorcontrib>Nicol, Alcina F</creatorcontrib><creatorcontrib>Cooper, Lynn D</creatorcontrib><creatorcontrib>Yearsley, Martha</creatorcontrib><creatorcontrib>Cordovil Pires, Andrea Rodrigues</creatorcontrib><creatorcontrib>Nuovo, Gerard J</creatorcontrib><title>Histologic, Viral, and Molecular Correlates of Dengue Fever Infection of the Liver Using Highly Sensitive Immunohistochemistry</title><title>Diagnostic molecular pathology</title><addtitle>Diagn Mol Pathol</addtitle><description>The mechanism by which the virus associated with dengue fever can cause a fatal hepatitis is not well understood. The purpose of this study was to examine 9 cases of fatal dengue hemorrhagic fever-associated hepatitis, and to correlate the histologic findings with viral detection and cytokine response. The histologic changes were nonspecific and included massive hepatic necrosis and a pauci-cellular acute hepatitis. Viral cDNA detection by reverse transcriptase in situ polymerase chain reaction demonstrated that the fatal hepatitis was due to infection on average of >90% of hepatocytes and many Kupffer cells. Similar results were obtained using immunohistochemistry for viral protein using an automated highly sensitive system. Immunohistochemical analysis for tumor necrosis factor α, and interleukin-2, showed rare positive Kupffer cells. In comparison, fatal cases of hepatitis C associated liver failure demonstrated far fewer infected hepatocytes and a concomitant strong up-regulation of many cytokines, notably tumor necrosis factor α and interleukin-2. It is concluded that fatal dengue hemorrhagic fever is associated with acute, severe liver damage due primarily to massive direct infection of hepatocytes and Kupffer cells with minimal cytokine response. The infection can be readily detected in a few hours using an automated system that has a sensitivity equivalent to reverse transcriptase in situ polymerase chain reaction.</description><subject>Dengue Virus - genetics</subject><subject>Dengue Virus - isolation & purification</subject><subject>Hepatitis, Viral, Human - etiology</subject><subject>Hepatitis, Viral, Human - metabolism</subject><subject>Hepatitis, Viral, Human - pathology</subject><subject>Hepatitis, Viral, Human - virology</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Interleukin-2 - analysis</subject><subject>Liver - chemistry</subject><subject>Liver - pathology</subject><subject>Liver - virology</subject><subject>Necrosis</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Viral - analysis</subject><subject>Severe Dengue - complications</subject><subject>Severe Dengue - metabolism</subject><subject>Severe Dengue - pathology</subject><subject>Severe Dengue - virology</subject><subject>Tumor Necrosis Factor-alpha - analysis</subject><subject>Viral Proteins - analysis</subject><issn>1052-9551</issn><issn>1533-4066</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkEGP0zAQhSMEYpeFv4AsDpw2YSaOnYQbKiytVMQBlqvl2tMm4MTFTlj1wm_HoZXWB89o_M178suyNwgFQlu_AyyOdiggnRJ5JctCgqxEYeyT7BoF53kFUj5NPYgyb4XAq-xFjD8Tz6tGPM-usMaylAKus7_rPk7e-UNvbtmPPmh3y_Ro2RfvyMxOB7byIZDTE0Xm9-wjjYeZ2B39ocA2457M1PtxeZk6Ytt-Gd_HfjywdX_o3Il9ozH2U5qzzTDMo-8WP9PRkGo4vcye7bWL9OpSb7L7u0_fV-t8-_XzZvVhmxsuS5HznUUwVqKtdQN1XROvsSWUurVg6lZo1JQ-B3LXiJbsjmtOgEI3bSn2BvhN9vasewz-90xxUsnfkHN6JD9HJRtssBQige_PoAk-xkB7dQz9oMNJIaglfQWoUvrqMX31P31lbFp-fXGZdwPZx9VL3AmozsCDdxOF-MvNDxRUR9pN3SKJbRLLSwCJ6YJ8cRH8H1NYku8</recordid><startdate>200612</startdate><enddate>200612</enddate><creator>Carvalho de Macedo, Fabiane</creator><creator>Nicol, Alcina F</creator><creator>Cooper, Lynn D</creator><creator>Yearsley, Martha</creator><creator>Cordovil Pires, Andrea Rodrigues</creator><creator>Nuovo, Gerard J</creator><general>Lippincott Williams & Wilkins, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>200612</creationdate><title>Histologic, Viral, and Molecular Correlates of Dengue Fever Infection of the Liver Using Highly Sensitive Immunohistochemistry</title><author>Carvalho de Macedo, Fabiane ; Nicol, Alcina F ; Cooper, Lynn D ; Yearsley, Martha ; Cordovil Pires, Andrea Rodrigues ; Nuovo, Gerard J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3625-3bd10cd61d7a80777e3719e16a9d0c795a1ae03406b859edb3a3e015a8925fc03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Dengue Virus - genetics</topic><topic>Dengue Virus - isolation & purification</topic><topic>Hepatitis, Viral, Human - etiology</topic><topic>Hepatitis, Viral, Human - metabolism</topic><topic>Hepatitis, Viral, Human - pathology</topic><topic>Hepatitis, Viral, Human - virology</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Interleukin-2 - analysis</topic><topic>Liver - chemistry</topic><topic>Liver - pathology</topic><topic>Liver - virology</topic><topic>Necrosis</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Viral - analysis</topic><topic>Severe Dengue - complications</topic><topic>Severe Dengue - metabolism</topic><topic>Severe Dengue - pathology</topic><topic>Severe Dengue - virology</topic><topic>Tumor Necrosis Factor-alpha - analysis</topic><topic>Viral Proteins - analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Carvalho de Macedo, Fabiane</creatorcontrib><creatorcontrib>Nicol, Alcina F</creatorcontrib><creatorcontrib>Cooper, Lynn D</creatorcontrib><creatorcontrib>Yearsley, Martha</creatorcontrib><creatorcontrib>Cordovil Pires, Andrea Rodrigues</creatorcontrib><creatorcontrib>Nuovo, Gerard J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Diagnostic molecular pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Carvalho de Macedo, Fabiane</au><au>Nicol, Alcina F</au><au>Cooper, Lynn D</au><au>Yearsley, Martha</au><au>Cordovil Pires, Andrea Rodrigues</au><au>Nuovo, Gerard J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Histologic, Viral, and Molecular Correlates of Dengue Fever Infection of the Liver Using Highly Sensitive Immunohistochemistry</atitle><jtitle>Diagnostic molecular pathology</jtitle><addtitle>Diagn Mol Pathol</addtitle><date>2006-12</date><risdate>2006</risdate><volume>15</volume><issue>4</issue><spage>223</spage><epage>228</epage><pages>223-228</pages><issn>1052-9551</issn><eissn>1533-4066</eissn><abstract>The mechanism by which the virus associated with dengue fever can cause a fatal hepatitis is not well understood. The purpose of this study was to examine 9 cases of fatal dengue hemorrhagic fever-associated hepatitis, and to correlate the histologic findings with viral detection and cytokine response. The histologic changes were nonspecific and included massive hepatic necrosis and a pauci-cellular acute hepatitis. Viral cDNA detection by reverse transcriptase in situ polymerase chain reaction demonstrated that the fatal hepatitis was due to infection on average of >90% of hepatocytes and many Kupffer cells. Similar results were obtained using immunohistochemistry for viral protein using an automated highly sensitive system. Immunohistochemical analysis for tumor necrosis factor α, and interleukin-2, showed rare positive Kupffer cells. In comparison, fatal cases of hepatitis C associated liver failure demonstrated far fewer infected hepatocytes and a concomitant strong up-regulation of many cytokines, notably tumor necrosis factor α and interleukin-2. It is concluded that fatal dengue hemorrhagic fever is associated with acute, severe liver damage due primarily to massive direct infection of hepatocytes and Kupffer cells with minimal cytokine response. The infection can be readily detected in a few hours using an automated system that has a sensitivity equivalent to reverse transcriptase in situ polymerase chain reaction.</abstract><cop>United States</cop><pub>Lippincott Williams & Wilkins, Inc</pub><pmid>17122650</pmid><doi>10.1097/01.pdm.0000213462.60645.cd</doi><tpages>6</tpages></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1052-9551 |
ispartof | Diagnostic molecular pathology, 2006-12, Vol.15 (4), p.223-228 |
issn | 1052-9551 1533-4066 |
language | eng |
recordid | cdi_proquest_miscellaneous_68181255 |
source | MEDLINE; Journals@Ovid Complete |
subjects | Dengue Virus - genetics Dengue Virus - isolation & purification Hepatitis, Viral, Human - etiology Hepatitis, Viral, Human - metabolism Hepatitis, Viral, Human - pathology Hepatitis, Viral, Human - virology Humans Immunohistochemistry Interleukin-2 - analysis Liver - chemistry Liver - pathology Liver - virology Necrosis Reverse Transcriptase Polymerase Chain Reaction RNA, Viral - analysis Severe Dengue - complications Severe Dengue - metabolism Severe Dengue - pathology Severe Dengue - virology Tumor Necrosis Factor-alpha - analysis Viral Proteins - analysis |
title | Histologic, Viral, and Molecular Correlates of Dengue Fever Infection of the Liver Using Highly Sensitive Immunohistochemistry |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-24T01%3A53%3A25IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Histologic,%20Viral,%20and%20Molecular%20Correlates%20of%20Dengue%20Fever%20Infection%20of%20the%20Liver%20Using%20Highly%20Sensitive%20Immunohistochemistry&rft.jtitle=Diagnostic%20molecular%20pathology&rft.au=Carvalho%20de%20Macedo,%20Fabiane&rft.date=2006-12&rft.volume=15&rft.issue=4&rft.spage=223&rft.epage=228&rft.pages=223-228&rft.issn=1052-9551&rft.eissn=1533-4066&rft_id=info:doi/10.1097/01.pdm.0000213462.60645.cd&rft_dat=%3Cproquest_cross%3E68181255%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=68181255&rft_id=info:pmid/17122650&rfr_iscdi=true |