Circulating levels of endotrophin and cross-linked type III collagen reflect liver fibrosis in people with HIV

Abstract Background and aims Liver-associated complications still frequently lead to mortality in people with HIV (PWH), even though combined antiretroviral treatment (cART) has significantly improved overall survival. The quantification of circulating collagen fragments released during collagen for...

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Main Authors: Leona Dold, Mette J. Nielsen, Michael Praktiknjo, Carolynne Schwarze-Zander, Christoph Boesecke, Jan-Christian Wasmuth, Jenny Bischoff, Jürgen Kurt Rockstroh, Morten A. Karsdal, Ulrich Spengler, Jonel Trebicka, Christian P. Strassburg, Diana J. Leeming, Bettina Langhans
Format: Article
Language:English
Published: BMC 2023-01-01
Series:BMC Infectious Diseases
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Online Access:https://doi.org/10.1186/s12879-023-08000-w
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author Leona Dold
Mette J. Nielsen
Michael Praktiknjo
Carolynne Schwarze-Zander
Christoph Boesecke
Jan-Christian Wasmuth
Jenny Bischoff
Jürgen Kurt Rockstroh
Morten A. Karsdal
Ulrich Spengler
Jonel Trebicka
Christian P. Strassburg
Diana J. Leeming
Bettina Langhans
author_facet Leona Dold
Mette J. Nielsen
Michael Praktiknjo
Carolynne Schwarze-Zander
Christoph Boesecke
Jan-Christian Wasmuth
Jenny Bischoff
Jürgen Kurt Rockstroh
Morten A. Karsdal
Ulrich Spengler
Jonel Trebicka
Christian P. Strassburg
Diana J. Leeming
Bettina Langhans
author_sort Leona Dold
collection DOAJ
description Abstract Background and aims Liver-associated complications still frequently lead to mortality in people with HIV (PWH), even though combined antiretroviral treatment (cART) has significantly improved overall survival. The quantification of circulating collagen fragments released during collagen formation and degradation correlate with the turnover of extracellular matrix (ECM) in liver disease. Here, we analysed the levels of ECM turnover markers PC3X, PRO-C5, and PRO-C6 in PWH and correlated these with hepatic fibrosis and steatosis. Methods This monocentre, retrospective study included 141 PWH. Liver stiffness and liver fat content were determined using transient elastography (Fibroscan) with integrated CAP function. Serum levels of formation of cross-linked type III collagen (PC3X), formation of type V collagen (PRO-C5) and formation type VI collagen (PRO-C6), also known as the hormone endotrophin, were measured with ELISA. Results Twenty-five (17.7%) of 141 PWH had clinical significant fibrosis with liver stiffness ≥ 7.1 kPa, and 62 PWH (44.0%) had steatosis with a CAP value > 238 dB/m. Study participants with fibrosis were older (p = 0.004) and had higher levels of AST (p = 0.037) and lower number of thrombocytes compared to individuals without fibrosis (p = 0.0001). PC3X and PRO-C6 were markedly elevated in PWH with fibrosis. Multivariable cox regression analysis confirmed PC3X as independently associated with hepatic fibrosis. PRO-C5 was significantly elevated in participants with presence of hepatic steatosis. Conclusion Serological levels of cross-linked type III collagen formation and endotrophin were significantly associated with liver fibrosis in PWH receiving cART and thus may be suitable as a non-invasive evaluation of liver fibrosis in HIV disease.
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spelling doaj.art-a44fd9ba1d1f4da09ed1aa2b273400102023-01-29T12:05:23ZengBMCBMC Infectious Diseases1471-23342023-01-012311910.1186/s12879-023-08000-wCirculating levels of endotrophin and cross-linked type III collagen reflect liver fibrosis in people with HIVLeona Dold0Mette J. Nielsen1Michael Praktiknjo2Carolynne Schwarze-Zander3Christoph Boesecke4Jan-Christian Wasmuth5Jenny Bischoff6Jürgen Kurt Rockstroh7Morten A. Karsdal8Ulrich Spengler9Jonel Trebicka10Christian P. Strassburg11Diana J. Leeming12Bettina Langhans13Department of Internal Medicine I, University Hospital of BonnNordic Bioscience, Fibrosis Biology and BiomarkersDepartment of Internal Medicine B, University Hospital of MünsterDepartment of Internal Medicine I, University Hospital of BonnDepartment of Internal Medicine I, University Hospital of BonnDepartment of Internal Medicine I, University Hospital of BonnDepartment of Internal Medicine I, University Hospital of BonnDepartment of Internal Medicine I, University Hospital of BonnNordic Bioscience, Fibrosis Biology and BiomarkersDepartment of Internal Medicine I, University Hospital of BonnDepartment of Internal Medicine B, University Hospital of MünsterDepartment of Internal Medicine I, University Hospital of BonnNordic Bioscience, Fibrosis Biology and BiomarkersDepartment of Internal Medicine I, University Hospital of BonnAbstract Background and aims Liver-associated complications still frequently lead to mortality in people with HIV (PWH), even though combined antiretroviral treatment (cART) has significantly improved overall survival. The quantification of circulating collagen fragments released during collagen formation and degradation correlate with the turnover of extracellular matrix (ECM) in liver disease. Here, we analysed the levels of ECM turnover markers PC3X, PRO-C5, and PRO-C6 in PWH and correlated these with hepatic fibrosis and steatosis. Methods This monocentre, retrospective study included 141 PWH. Liver stiffness and liver fat content were determined using transient elastography (Fibroscan) with integrated CAP function. Serum levels of formation of cross-linked type III collagen (PC3X), formation of type V collagen (PRO-C5) and formation type VI collagen (PRO-C6), also known as the hormone endotrophin, were measured with ELISA. Results Twenty-five (17.7%) of 141 PWH had clinical significant fibrosis with liver stiffness ≥ 7.1 kPa, and 62 PWH (44.0%) had steatosis with a CAP value > 238 dB/m. Study participants with fibrosis were older (p = 0.004) and had higher levels of AST (p = 0.037) and lower number of thrombocytes compared to individuals without fibrosis (p = 0.0001). PC3X and PRO-C6 were markedly elevated in PWH with fibrosis. Multivariable cox regression analysis confirmed PC3X as independently associated with hepatic fibrosis. PRO-C5 was significantly elevated in participants with presence of hepatic steatosis. Conclusion Serological levels of cross-linked type III collagen formation and endotrophin were significantly associated with liver fibrosis in PWH receiving cART and thus may be suitable as a non-invasive evaluation of liver fibrosis in HIV disease.https://doi.org/10.1186/s12879-023-08000-wPC3XPRO-C5PRO-C6HIVLiver fibrosisHepatic steatosis
spellingShingle Leona Dold
Mette J. Nielsen
Michael Praktiknjo
Carolynne Schwarze-Zander
Christoph Boesecke
Jan-Christian Wasmuth
Jenny Bischoff
Jürgen Kurt Rockstroh
Morten A. Karsdal
Ulrich Spengler
Jonel Trebicka
Christian P. Strassburg
Diana J. Leeming
Bettina Langhans
Circulating levels of endotrophin and cross-linked type III collagen reflect liver fibrosis in people with HIV
BMC Infectious Diseases
PC3X
PRO-C5
PRO-C6
HIV
Liver fibrosis
Hepatic steatosis
title Circulating levels of endotrophin and cross-linked type III collagen reflect liver fibrosis in people with HIV
title_full Circulating levels of endotrophin and cross-linked type III collagen reflect liver fibrosis in people with HIV
title_fullStr Circulating levels of endotrophin and cross-linked type III collagen reflect liver fibrosis in people with HIV
title_full_unstemmed Circulating levels of endotrophin and cross-linked type III collagen reflect liver fibrosis in people with HIV
title_short Circulating levels of endotrophin and cross-linked type III collagen reflect liver fibrosis in people with HIV
title_sort circulating levels of endotrophin and cross linked type iii collagen reflect liver fibrosis in people with hiv
topic PC3X
PRO-C5
PRO-C6
HIV
Liver fibrosis
Hepatic steatosis
url https://doi.org/10.1186/s12879-023-08000-w
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