Systemic inflammation and liver damage in HIV/hepatitis C virus coinfection

Objectives Chronic hepatitis C virus (HCV) and HIV viral infections are characterized by systemic inflammation. Yet the relative levels, drivers and correlates of inflammation in these settings are not well defined. Methods Seventy‐nine HIV‐infected patients who had been receiving antiretroviral the...

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Veröffentlicht in:HIV medicine 2016-09, Vol.17 (8), p.581-589
Hauptverfasser: Shmagel, KV, Saidakova, EV, Shmagel, NG, Korolevskaya, LB, Chereshnev, VA, Robinson, J, Grivel, J‐C, Douek, DC, Margolis, L, Anthony, DD, Lederman, MM
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container_end_page 589
container_issue 8
container_start_page 581
container_title HIV medicine
container_volume 17
creator Shmagel, KV
Saidakova, EV
Shmagel, NG
Korolevskaya, LB
Chereshnev, VA
Robinson, J
Grivel, J‐C
Douek, DC
Margolis, L
Anthony, DD
Lederman, MM
description Objectives Chronic hepatitis C virus (HCV) and HIV viral infections are characterized by systemic inflammation. Yet the relative levels, drivers and correlates of inflammation in these settings are not well defined. Methods Seventy‐nine HIV‐infected patients who had been receiving antiretroviral therapy (ART) for more than 2 years and who had suppressed plasma HIV levels (< 50 HIV‐1 RNA copies/mL) were included in the study. Two patient groups, HCV‐positive/HIV‐positive and HCV‐negative/HIV‐positive, and a control group comprised of healthy volunteers (n = 20) were examined. Markers of systemic inflammation [interleukin (IL)‐6, interferon gamma‐induced protein (IP)‐10, soluble tumour necrosis factor receptor‐I (sTNF‐RI) and sTNF‐RII], monocyte/macrophage activation [soluble CD163 (sCD163), soluble CD14 and neopterin], intestinal epithelial barrier loss [intestinal fatty acid binding protein (I‐FABP) and lipopolysaccharide (LPS)] and coagulation (d‐dimers) were analysed. CD4 naïve T cells and CD4 recent thymic emigrants (RTEs) were enumerated. Results Plasma levels of IP‐10, neopterin and sCD163 were higher in HCV/HIV coinfection than in HIV monoinfection and were positively correlated with indices of hepatic damage [aspartate aminotransferase (AST), alanine aminotransferase (ALT) and the AST to platelet ratio index (APRI)]. Levels of I‐FABP were comparably increased in HIV monoinfection and HIV/HCV coinfection but LPS concentrations were highest in HCV/HIV coinfection, suggesting impaired hepatic clearance of LPS. Plasma HCV levels were not related to any inflammatory indices except sCD163. In coinfected subjects, a previously recognized relationship of CD4 naïve T‐cell and RTE counts to hepatocellular injury was defined more mechanistically by an inverse relationship to sCD163. Conclusions Hepatocellular injury in HCV/HIV coinfection is linked to elevated levels of certain inflammatory cytokines and an apparent failure to clear systemically translocated microbial products. A related decrease in CD4 naïve T cells and RTEs also merits further exploration.
doi_str_mv 10.1111/hiv.12357
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Yet the relative levels, drivers and correlates of inflammation in these settings are not well defined. Methods Seventy‐nine HIV‐infected patients who had been receiving antiretroviral therapy (ART) for more than 2 years and who had suppressed plasma HIV levels (&lt; 50 HIV‐1 RNA copies/mL) were included in the study. Two patient groups, HCV‐positive/HIV‐positive and HCV‐negative/HIV‐positive, and a control group comprised of healthy volunteers (n = 20) were examined. Markers of systemic inflammation [interleukin (IL)‐6, interferon gamma‐induced protein (IP)‐10, soluble tumour necrosis factor receptor‐I (sTNF‐RI) and sTNF‐RII], monocyte/macrophage activation [soluble CD163 (sCD163), soluble CD14 and neopterin], intestinal epithelial barrier loss [intestinal fatty acid binding protein (I‐FABP) and lipopolysaccharide (LPS)] and coagulation (d‐dimers) were analysed. CD4 naïve T cells and CD4 recent thymic emigrants (RTEs) were enumerated. Results Plasma levels of IP‐10, neopterin and sCD163 were higher in HCV/HIV coinfection than in HIV monoinfection and were positively correlated with indices of hepatic damage [aspartate aminotransferase (AST), alanine aminotransferase (ALT) and the AST to platelet ratio index (APRI)]. Levels of I‐FABP were comparably increased in HIV monoinfection and HIV/HCV coinfection but LPS concentrations were highest in HCV/HIV coinfection, suggesting impaired hepatic clearance of LPS. Plasma HCV levels were not related to any inflammatory indices except sCD163. In coinfected subjects, a previously recognized relationship of CD4 naïve T‐cell and RTE counts to hepatocellular injury was defined more mechanistically by an inverse relationship to sCD163. Conclusions Hepatocellular injury in HCV/HIV coinfection is linked to elevated levels of certain inflammatory cytokines and an apparent failure to clear systemically translocated microbial products. A related decrease in CD4 naïve T cells and RTEs also merits further exploration.</description><identifier>ISSN: 1464-2662</identifier><identifier>EISSN: 1468-1293</identifier><identifier>DOI: 10.1111/hiv.12357</identifier><identifier>PMID: 27187749</identifier><language>eng</language><publisher>England</publisher><subject>Adult ; antigens ; Biomarkers - blood ; CD31 ; Coinfection - pathology ; Cytokines - blood ; Female ; hepatitis C ; Hepatitis C virus ; Hepatitis C, Chronic - complications ; Hepatitis C, Chronic - pathology ; highly active antiretroviral therapy ; HIV infections ; HIV Infections - complications ; HIV Infections - pathology ; Humans ; Inflammation - pathology ; inflammation mediators ; Lentivirus ; Liver - pathology ; Male</subject><ispartof>HIV medicine, 2016-09, Vol.17 (8), p.581-589</ispartof><rights>2016 British HIV Association</rights><rights>2016 British HIV Association.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4637-b3ac7a825e336c2108083acbbc3837fa1cc45cdff09cf7dea083282b9d3ecf513</citedby><cites>FETCH-LOGICAL-c4637-b3ac7a825e336c2108083acbbc3837fa1cc45cdff09cf7dea083282b9d3ecf513</cites><orcidid>0000-0002-4342-5362</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fhiv.12357$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fhiv.12357$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,1433,27924,27925,45574,45575,46409,46833</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27187749$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shmagel, KV</creatorcontrib><creatorcontrib>Saidakova, EV</creatorcontrib><creatorcontrib>Shmagel, NG</creatorcontrib><creatorcontrib>Korolevskaya, LB</creatorcontrib><creatorcontrib>Chereshnev, VA</creatorcontrib><creatorcontrib>Robinson, J</creatorcontrib><creatorcontrib>Grivel, J‐C</creatorcontrib><creatorcontrib>Douek, DC</creatorcontrib><creatorcontrib>Margolis, L</creatorcontrib><creatorcontrib>Anthony, DD</creatorcontrib><creatorcontrib>Lederman, MM</creatorcontrib><title>Systemic inflammation and liver damage in HIV/hepatitis C virus coinfection</title><title>HIV medicine</title><addtitle>HIV Med</addtitle><description>Objectives Chronic hepatitis C virus (HCV) and HIV viral infections are characterized by systemic inflammation. 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Results Plasma levels of IP‐10, neopterin and sCD163 were higher in HCV/HIV coinfection than in HIV monoinfection and were positively correlated with indices of hepatic damage [aspartate aminotransferase (AST), alanine aminotransferase (ALT) and the AST to platelet ratio index (APRI)]. Levels of I‐FABP were comparably increased in HIV monoinfection and HIV/HCV coinfection but LPS concentrations were highest in HCV/HIV coinfection, suggesting impaired hepatic clearance of LPS. Plasma HCV levels were not related to any inflammatory indices except sCD163. In coinfected subjects, a previously recognized relationship of CD4 naïve T‐cell and RTE counts to hepatocellular injury was defined more mechanistically by an inverse relationship to sCD163. Conclusions Hepatocellular injury in HCV/HIV coinfection is linked to elevated levels of certain inflammatory cytokines and an apparent failure to clear systemically translocated microbial products. 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Saidakova, EV ; Shmagel, NG ; Korolevskaya, LB ; Chereshnev, VA ; Robinson, J ; Grivel, J‐C ; Douek, DC ; Margolis, L ; Anthony, DD ; Lederman, MM</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4637-b3ac7a825e336c2108083acbbc3837fa1cc45cdff09cf7dea083282b9d3ecf513</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adult</topic><topic>antigens</topic><topic>Biomarkers - blood</topic><topic>CD31</topic><topic>Coinfection - pathology</topic><topic>Cytokines - blood</topic><topic>Female</topic><topic>hepatitis C</topic><topic>Hepatitis C virus</topic><topic>Hepatitis C, Chronic - complications</topic><topic>Hepatitis C, Chronic - pathology</topic><topic>highly active antiretroviral therapy</topic><topic>HIV infections</topic><topic>HIV Infections - complications</topic><topic>HIV Infections - pathology</topic><topic>Humans</topic><topic>Inflammation - pathology</topic><topic>inflammation mediators</topic><topic>Lentivirus</topic><topic>Liver - pathology</topic><topic>Male</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shmagel, KV</creatorcontrib><creatorcontrib>Saidakova, EV</creatorcontrib><creatorcontrib>Shmagel, NG</creatorcontrib><creatorcontrib>Korolevskaya, LB</creatorcontrib><creatorcontrib>Chereshnev, VA</creatorcontrib><creatorcontrib>Robinson, J</creatorcontrib><creatorcontrib>Grivel, J‐C</creatorcontrib><creatorcontrib>Douek, DC</creatorcontrib><creatorcontrib>Margolis, L</creatorcontrib><creatorcontrib>Anthony, DD</creatorcontrib><creatorcontrib>Lederman, MM</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><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>HIV medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shmagel, KV</au><au>Saidakova, EV</au><au>Shmagel, NG</au><au>Korolevskaya, LB</au><au>Chereshnev, VA</au><au>Robinson, J</au><au>Grivel, J‐C</au><au>Douek, DC</au><au>Margolis, L</au><au>Anthony, DD</au><au>Lederman, MM</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Systemic inflammation and liver damage in HIV/hepatitis C virus coinfection</atitle><jtitle>HIV medicine</jtitle><addtitle>HIV Med</addtitle><date>2016-09</date><risdate>2016</risdate><volume>17</volume><issue>8</issue><spage>581</spage><epage>589</epage><pages>581-589</pages><issn>1464-2662</issn><eissn>1468-1293</eissn><abstract>Objectives Chronic hepatitis C virus (HCV) and HIV viral infections are characterized by systemic inflammation. Yet the relative levels, drivers and correlates of inflammation in these settings are not well defined. Methods Seventy‐nine HIV‐infected patients who had been receiving antiretroviral therapy (ART) for more than 2 years and who had suppressed plasma HIV levels (&lt; 50 HIV‐1 RNA copies/mL) were included in the study. Two patient groups, HCV‐positive/HIV‐positive and HCV‐negative/HIV‐positive, and a control group comprised of healthy volunteers (n = 20) were examined. Markers of systemic inflammation [interleukin (IL)‐6, interferon gamma‐induced protein (IP)‐10, soluble tumour necrosis factor receptor‐I (sTNF‐RI) and sTNF‐RII], monocyte/macrophage activation [soluble CD163 (sCD163), soluble CD14 and neopterin], intestinal epithelial barrier loss [intestinal fatty acid binding protein (I‐FABP) and lipopolysaccharide (LPS)] and coagulation (d‐dimers) were analysed. CD4 naïve T cells and CD4 recent thymic emigrants (RTEs) were enumerated. Results Plasma levels of IP‐10, neopterin and sCD163 were higher in HCV/HIV coinfection than in HIV monoinfection and were positively correlated with indices of hepatic damage [aspartate aminotransferase (AST), alanine aminotransferase (ALT) and the AST to platelet ratio index (APRI)]. Levels of I‐FABP were comparably increased in HIV monoinfection and HIV/HCV coinfection but LPS concentrations were highest in HCV/HIV coinfection, suggesting impaired hepatic clearance of LPS. Plasma HCV levels were not related to any inflammatory indices except sCD163. In coinfected subjects, a previously recognized relationship of CD4 naïve T‐cell and RTE counts to hepatocellular injury was defined more mechanistically by an inverse relationship to sCD163. Conclusions Hepatocellular injury in HCV/HIV coinfection is linked to elevated levels of certain inflammatory cytokines and an apparent failure to clear systemically translocated microbial products. A related decrease in CD4 naïve T cells and RTEs also merits further exploration.</abstract><cop>England</cop><pmid>27187749</pmid><doi>10.1111/hiv.12357</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-4342-5362</orcidid><oa>free_for_read</oa></addata></record>
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subjects Adult
antigens
Biomarkers - blood
CD31
Coinfection - pathology
Cytokines - blood
Female
hepatitis C
Hepatitis C virus
Hepatitis C, Chronic - complications
Hepatitis C, Chronic - pathology
highly active antiretroviral therapy
HIV infections
HIV Infections - complications
HIV Infections - pathology
Humans
Inflammation - pathology
inflammation mediators
Lentivirus
Liver - pathology
Male
title Systemic inflammation and liver damage in HIV/hepatitis C virus coinfection
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