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...
Main Authors: | , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2023-01-01
|
Series: | BMC Infectious Diseases |
Subjects: | |
Online Access: | https://doi.org/10.1186/s12879-023-08000-w |
_version_ | 1811175955020906496 |
---|---|
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. |
first_indexed | 2024-04-10T19:45:29Z |
format | Article |
id | doaj.art-a44fd9ba1d1f4da09ed1aa2b27340010 |
institution | Directory Open Access Journal |
issn | 1471-2334 |
language | English |
last_indexed | 2024-04-10T19:45:29Z |
publishDate | 2023-01-01 |
publisher | BMC |
record_format | Article |
series | BMC Infectious Diseases |
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 |
work_keys_str_mv | AT leonadold circulatinglevelsofendotrophinandcrosslinkedtypeiiicollagenreflectliverfibrosisinpeoplewithhiv AT mettejnielsen circulatinglevelsofendotrophinandcrosslinkedtypeiiicollagenreflectliverfibrosisinpeoplewithhiv AT michaelpraktiknjo circulatinglevelsofendotrophinandcrosslinkedtypeiiicollagenreflectliverfibrosisinpeoplewithhiv AT carolynneschwarzezander circulatinglevelsofendotrophinandcrosslinkedtypeiiicollagenreflectliverfibrosisinpeoplewithhiv AT christophboesecke circulatinglevelsofendotrophinandcrosslinkedtypeiiicollagenreflectliverfibrosisinpeoplewithhiv AT janchristianwasmuth circulatinglevelsofendotrophinandcrosslinkedtypeiiicollagenreflectliverfibrosisinpeoplewithhiv AT jennybischoff circulatinglevelsofendotrophinandcrosslinkedtypeiiicollagenreflectliverfibrosisinpeoplewithhiv AT jurgenkurtrockstroh circulatinglevelsofendotrophinandcrosslinkedtypeiiicollagenreflectliverfibrosisinpeoplewithhiv AT mortenakarsdal circulatinglevelsofendotrophinandcrosslinkedtypeiiicollagenreflectliverfibrosisinpeoplewithhiv AT ulrichspengler circulatinglevelsofendotrophinandcrosslinkedtypeiiicollagenreflectliverfibrosisinpeoplewithhiv AT joneltrebicka circulatinglevelsofendotrophinandcrosslinkedtypeiiicollagenreflectliverfibrosisinpeoplewithhiv AT christianpstrassburg circulatinglevelsofendotrophinandcrosslinkedtypeiiicollagenreflectliverfibrosisinpeoplewithhiv AT dianajleeming circulatinglevelsofendotrophinandcrosslinkedtypeiiicollagenreflectliverfibrosisinpeoplewithhiv AT bettinalanghans circulatinglevelsofendotrophinandcrosslinkedtypeiiicollagenreflectliverfibrosisinpeoplewithhiv |