Circulating levels of PRO-C3 reflect liver fibrosis and liver function in HIV positive patients receiving modern cART
Although combined antiretroviral treatment (cART) has improved overall survival of HIV infected patients, liver fibrosis and liver related-mortality still constitute major challenges in HIV positive patients. Collagen accumulates in the liver during fibrogenesis. Recent studies showed that circulati...
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| Veröffentlicht in: | PloS one 2019-07, Vol.14 (7), p.e0219526-e0219526 |
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| creator | Dold, Leona Nielsen, Mette J Praktiknjo, Michael Schwarze-Zander, Carolynne Boesecke, Christoph Schierwagen, Robert Mohr, Raphael Wasmuth, Jan-Christian Jansen, Christian Bischoff, Jenny Rockstroh, Jürgen Kurt Karsdal, Morten A Spengler, Ulrich Trebicka, Jonel Leeming, Diana J |
| description | Although combined antiretroviral treatment (cART) has improved overall survival of HIV infected patients, liver fibrosis and liver related-mortality still constitute major challenges in HIV positive patients. Collagen accumulates in the liver during fibrogenesis. Recent studies showed that circulating levels of extracellular matrix (ECM) fragments might reflect degree of portal hypertension and fibrosis stage in liver disease. In this study, we analyzed the correlation between liver fibrosis assessed by Fibroscan and levels of the formation and degradation markers of type III and IV collagen in HIV positive patients receiving cART.
116 HIV positive patients (82.7% male, median age 47 years) were enrolled into the study. Liver stiffness and liver fat content were determined using a Fibroscan with integrated CAP function. We quantified ECM formation and degradation fragments of collagen III and IV: PRO-C3, PRO-C4, C3M and C4M. These fragments were measured in peripheral serum by using specific ELISAs.
Fifteen (12.9%) out of the 116 HIV positive patients had relevant fibrosis with a liver stiffness ≥ 7.1 kPa, and 79 patients had relevant steatosis with a CAP value > 248 dB/m. Circulating PRO-C3 levels significantly correlated with increasing degree of liver fibrosis assessed by Fibroscan (p = 0.0005), as well as with APRI score (p = 0.015). Interestingly, circulating PRO-C3 levels were significantly correlated with bilirubin (p = 0.022), reduced platelet count (p = 0.0008) and low albumin levels (p = 0.001), suggesting the association of type III collagen deposition with impaired liver function. None of the other measured ECM components significantly correlated with fibrosis or steatosis.
The formation marker of type III collagen, PRO-C3 not only reflects liver fibrosis, but might also mirror liver dysfunction in HIV positive patients receiving cART. Therefore, the circulating levels of PRO-C3 might be suitable to monitor progression of liver fibrosis and deterioration of liver function in HIV positive patients receiving cART. |
| doi_str_mv | 10.1371/journal.pone.0219526 |
| format | Article |
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116 HIV positive patients (82.7% male, median age 47 years) were enrolled into the study. Liver stiffness and liver fat content were determined using a Fibroscan with integrated CAP function. We quantified ECM formation and degradation fragments of collagen III and IV: PRO-C3, PRO-C4, C3M and C4M. These fragments were measured in peripheral serum by using specific ELISAs.
Fifteen (12.9%) out of the 116 HIV positive patients had relevant fibrosis with a liver stiffness ≥ 7.1 kPa, and 79 patients had relevant steatosis with a CAP value > 248 dB/m. Circulating PRO-C3 levels significantly correlated with increasing degree of liver fibrosis assessed by Fibroscan (p = 0.0005), as well as with APRI score (p = 0.015). Interestingly, circulating PRO-C3 levels were significantly correlated with bilirubin (p = 0.022), reduced platelet count (p = 0.0008) and low albumin levels (p = 0.001), suggesting the association of type III collagen deposition with impaired liver function. None of the other measured ECM components significantly correlated with fibrosis or steatosis.
The formation marker of type III collagen, PRO-C3 not only reflects liver fibrosis, but might also mirror liver dysfunction in HIV positive patients receiving cART. Therefore, the circulating levels of PRO-C3 might be suitable to monitor progression of liver fibrosis and deterioration of liver function in HIV positive patients receiving cART.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0219526</identifier><identifier>PMID: 31295293</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Albumin ; Alcohol ; Anti-Retroviral Agents - administration & dosage ; Antiretroviral agents ; Antiretroviral Therapy, Highly Active ; Bilirubin ; Biological markers ; Biology ; Biology and Life Sciences ; Biomarkers ; Biomarkers - blood ; Collagen ; Collagen (type III) ; Collagen Type III - blood ; Collagen Type IV - blood ; Complement C3 - metabolism ; Complement C4 - metabolism ; Complications and side effects ; Correlation analysis ; Degradation ; Demographic aspects ; Development and progression ; Disease Progression ; Drug therapy ; Enzyme-Linked Immunosorbent Assay ; Extracellular matrix ; Extracellular Matrix - genetics ; Fatty Liver - blood ; Fatty Liver - pathology ; Fatty Liver - virology ; Female ; Fibrosis ; Fragments ; Health aspects ; Hepatitis ; Hepatology ; Highly active antiretroviral therapy ; HIV ; HIV - genetics ; HIV - pathogenicity ; HIV infections ; HIV Infections - blood ; HIV Infections - drug therapy ; HIV Infections - pathology ; HIV Infections - virology ; HIV patients ; Human immunodeficiency virus ; Humans ; Hypertension ; Infections ; Internal medicine ; Liver ; Liver - metabolism ; Liver - pathology ; Liver Cirrhosis - blood ; Liver Cirrhosis - pathology ; Liver Cirrhosis - virology ; Liver diseases ; Male ; Medical research ; Medicine ; Medicine and Health Sciences ; Middle Aged ; Mortality ; Patients ; Portal hypertension ; Risk factors ; Steatosis ; Stiffness</subject><ispartof>PloS one, 2019-07, Vol.14 (7), p.e0219526-e0219526</ispartof><rights>COPYRIGHT 2019 Public Library of Science</rights><rights>2019 Dold et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2019 Dold et al 2019 Dold et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-e767ae2b26453ec6fde736191aabc475726f1d8b1e16b8c2799e64b53e78da373</citedby><orcidid>0000-0002-7677-3347 ; 0000-0002-7700-2915 ; 0000-0002-7028-3881</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6622522/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6622522/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31295293$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dold, Leona</creatorcontrib><creatorcontrib>Nielsen, Mette J</creatorcontrib><creatorcontrib>Praktiknjo, Michael</creatorcontrib><creatorcontrib>Schwarze-Zander, Carolynne</creatorcontrib><creatorcontrib>Boesecke, Christoph</creatorcontrib><creatorcontrib>Schierwagen, Robert</creatorcontrib><creatorcontrib>Mohr, Raphael</creatorcontrib><creatorcontrib>Wasmuth, Jan-Christian</creatorcontrib><creatorcontrib>Jansen, Christian</creatorcontrib><creatorcontrib>Bischoff, Jenny</creatorcontrib><creatorcontrib>Rockstroh, Jürgen Kurt</creatorcontrib><creatorcontrib>Karsdal, Morten A</creatorcontrib><creatorcontrib>Spengler, Ulrich</creatorcontrib><creatorcontrib>Trebicka, Jonel</creatorcontrib><creatorcontrib>Leeming, Diana J</creatorcontrib><title>Circulating levels of PRO-C3 reflect liver fibrosis and liver function in HIV positive patients receiving modern cART</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Although combined antiretroviral treatment (cART) has improved overall survival of HIV infected patients, liver fibrosis and liver related-mortality still constitute major challenges in HIV positive patients. Collagen accumulates in the liver during fibrogenesis. Recent studies showed that circulating levels of extracellular matrix (ECM) fragments might reflect degree of portal hypertension and fibrosis stage in liver disease. In this study, we analyzed the correlation between liver fibrosis assessed by Fibroscan and levels of the formation and degradation markers of type III and IV collagen in HIV positive patients receiving cART.
116 HIV positive patients (82.7% male, median age 47 years) were enrolled into the study. Liver stiffness and liver fat content were determined using a Fibroscan with integrated CAP function. We quantified ECM formation and degradation fragments of collagen III and IV: PRO-C3, PRO-C4, C3M and C4M. These fragments were measured in peripheral serum by using specific ELISAs.
Fifteen (12.9%) out of the 116 HIV positive patients had relevant fibrosis with a liver stiffness ≥ 7.1 kPa, and 79 patients had relevant steatosis with a CAP value > 248 dB/m. Circulating PRO-C3 levels significantly correlated with increasing degree of liver fibrosis assessed by Fibroscan (p = 0.0005), as well as with APRI score (p = 0.015). Interestingly, circulating PRO-C3 levels were significantly correlated with bilirubin (p = 0.022), reduced platelet count (p = 0.0008) and low albumin levels (p = 0.001), suggesting the association of type III collagen deposition with impaired liver function. None of the other measured ECM components significantly correlated with fibrosis or steatosis.
The formation marker of type III collagen, PRO-C3 not only reflects liver fibrosis, but might also mirror liver dysfunction in HIV positive patients receiving cART. Therefore, the circulating levels of PRO-C3 might be suitable to monitor progression of liver fibrosis and deterioration of liver function in HIV positive patients receiving cART.</description><subject>Adult</subject><subject>Albumin</subject><subject>Alcohol</subject><subject>Anti-Retroviral Agents - administration & dosage</subject><subject>Antiretroviral agents</subject><subject>Antiretroviral Therapy, Highly Active</subject><subject>Bilirubin</subject><subject>Biological markers</subject><subject>Biology</subject><subject>Biology and Life Sciences</subject><subject>Biomarkers</subject><subject>Biomarkers - blood</subject><subject>Collagen</subject><subject>Collagen (type III)</subject><subject>Collagen Type III - blood</subject><subject>Collagen Type IV - blood</subject><subject>Complement C3 - metabolism</subject><subject>Complement C4 - metabolism</subject><subject>Complications and side effects</subject><subject>Correlation analysis</subject><subject>Degradation</subject><subject>Demographic aspects</subject><subject>Development and progression</subject><subject>Disease Progression</subject><subject>Drug therapy</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Extracellular matrix</subject><subject>Extracellular Matrix - genetics</subject><subject>Fatty Liver - blood</subject><subject>Fatty Liver - pathology</subject><subject>Fatty Liver - virology</subject><subject>Female</subject><subject>Fibrosis</subject><subject>Fragments</subject><subject>Health aspects</subject><subject>Hepatitis</subject><subject>Hepatology</subject><subject>Highly active antiretroviral therapy</subject><subject>HIV</subject><subject>HIV - genetics</subject><subject>HIV - pathogenicity</subject><subject>HIV infections</subject><subject>HIV Infections - blood</subject><subject>HIV Infections - drug therapy</subject><subject>HIV Infections - pathology</subject><subject>HIV Infections - virology</subject><subject>HIV patients</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Hypertension</subject><subject>Infections</subject><subject>Internal medicine</subject><subject>Liver</subject><subject>Liver - metabolism</subject><subject>Liver - pathology</subject><subject>Liver Cirrhosis - blood</subject><subject>Liver Cirrhosis - 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genetics</topic><topic>HIV - pathogenicity</topic><topic>HIV infections</topic><topic>HIV Infections - blood</topic><topic>HIV Infections - drug therapy</topic><topic>HIV Infections - pathology</topic><topic>HIV Infections - virology</topic><topic>HIV patients</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>Hypertension</topic><topic>Infections</topic><topic>Internal medicine</topic><topic>Liver</topic><topic>Liver - metabolism</topic><topic>Liver - pathology</topic><topic>Liver Cirrhosis - blood</topic><topic>Liver Cirrhosis - pathology</topic><topic>Liver Cirrhosis - virology</topic><topic>Liver diseases</topic><topic>Male</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Middle Aged</topic><topic>Mortality</topic><topic>Patients</topic><topic>Portal hypertension</topic><topic>Risk factors</topic><topic>Steatosis</topic><topic>Stiffness</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dold, Leona</creatorcontrib><creatorcontrib>Nielsen, Mette J</creatorcontrib><creatorcontrib>Praktiknjo, Michael</creatorcontrib><creatorcontrib>Schwarze-Zander, Carolynne</creatorcontrib><creatorcontrib>Boesecke, Christoph</creatorcontrib><creatorcontrib>Schierwagen, Robert</creatorcontrib><creatorcontrib>Mohr, Raphael</creatorcontrib><creatorcontrib>Wasmuth, Jan-Christian</creatorcontrib><creatorcontrib>Jansen, Christian</creatorcontrib><creatorcontrib>Bischoff, Jenny</creatorcontrib><creatorcontrib>Rockstroh, Jürgen Kurt</creatorcontrib><creatorcontrib>Karsdal, Morten A</creatorcontrib><creatorcontrib>Spengler, Ulrich</creatorcontrib><creatorcontrib>Trebicka, Jonel</creatorcontrib><creatorcontrib>Leeming, Diana 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>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dold, Leona</au><au>Nielsen, Mette J</au><au>Praktiknjo, Michael</au><au>Schwarze-Zander, Carolynne</au><au>Boesecke, Christoph</au><au>Schierwagen, Robert</au><au>Mohr, Raphael</au><au>Wasmuth, Jan-Christian</au><au>Jansen, Christian</au><au>Bischoff, Jenny</au><au>Rockstroh, Jürgen Kurt</au><au>Karsdal, Morten A</au><au>Spengler, Ulrich</au><au>Trebicka, Jonel</au><au>Leeming, Diana J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Circulating levels of PRO-C3 reflect liver fibrosis and liver function in HIV positive patients receiving modern cART</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2019-07-11</date><risdate>2019</risdate><volume>14</volume><issue>7</issue><spage>e0219526</spage><epage>e0219526</epage><pages>e0219526-e0219526</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Although combined antiretroviral treatment (cART) has improved overall survival of HIV infected patients, liver fibrosis and liver related-mortality still constitute major challenges in HIV positive patients. Collagen accumulates in the liver during fibrogenesis. Recent studies showed that circulating levels of extracellular matrix (ECM) fragments might reflect degree of portal hypertension and fibrosis stage in liver disease. In this study, we analyzed the correlation between liver fibrosis assessed by Fibroscan and levels of the formation and degradation markers of type III and IV collagen in HIV positive patients receiving cART.
116 HIV positive patients (82.7% male, median age 47 years) were enrolled into the study. Liver stiffness and liver fat content were determined using a Fibroscan with integrated CAP function. We quantified ECM formation and degradation fragments of collagen III and IV: PRO-C3, PRO-C4, C3M and C4M. These fragments were measured in peripheral serum by using specific ELISAs.
Fifteen (12.9%) out of the 116 HIV positive patients had relevant fibrosis with a liver stiffness ≥ 7.1 kPa, and 79 patients had relevant steatosis with a CAP value > 248 dB/m. Circulating PRO-C3 levels significantly correlated with increasing degree of liver fibrosis assessed by Fibroscan (p = 0.0005), as well as with APRI score (p = 0.015). Interestingly, circulating PRO-C3 levels were significantly correlated with bilirubin (p = 0.022), reduced platelet count (p = 0.0008) and low albumin levels (p = 0.001), suggesting the association of type III collagen deposition with impaired liver function. None of the other measured ECM components significantly correlated with fibrosis or steatosis.
The formation marker of type III collagen, PRO-C3 not only reflects liver fibrosis, but might also mirror liver dysfunction in HIV positive patients receiving cART. Therefore, the circulating levels of PRO-C3 might be suitable to monitor progression of liver fibrosis and deterioration of liver function in HIV positive patients receiving cART.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>31295293</pmid><doi>10.1371/journal.pone.0219526</doi><tpages>e0219526</tpages><orcidid>https://orcid.org/0000-0002-7677-3347</orcidid><orcidid>https://orcid.org/0000-0002-7700-2915</orcidid><orcidid>https://orcid.org/0000-0002-7028-3881</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2019-07, Vol.14 (7), p.e0219526-e0219526 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2256175739 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Adult Albumin Alcohol Anti-Retroviral Agents - administration & dosage Antiretroviral agents Antiretroviral Therapy, Highly Active Bilirubin Biological markers Biology Biology and Life Sciences Biomarkers Biomarkers - blood Collagen Collagen (type III) Collagen Type III - blood Collagen Type IV - blood Complement C3 - metabolism Complement C4 - metabolism Complications and side effects Correlation analysis Degradation Demographic aspects Development and progression Disease Progression Drug therapy Enzyme-Linked Immunosorbent Assay Extracellular matrix Extracellular Matrix - genetics Fatty Liver - blood Fatty Liver - pathology Fatty Liver - virology Female Fibrosis Fragments Health aspects Hepatitis Hepatology Highly active antiretroviral therapy HIV HIV - genetics HIV - pathogenicity HIV infections HIV Infections - blood HIV Infections - drug therapy HIV Infections - pathology HIV Infections - virology HIV patients Human immunodeficiency virus Humans Hypertension Infections Internal medicine Liver Liver - metabolism Liver - pathology Liver Cirrhosis - blood Liver Cirrhosis - pathology Liver Cirrhosis - virology Liver diseases Male Medical research Medicine Medicine and Health Sciences Middle Aged Mortality Patients Portal hypertension Risk factors Steatosis Stiffness |
| title | Circulating levels of PRO-C3 reflect liver fibrosis and liver function in HIV positive patients receiving modern cART |
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