Circulating levels of PRO-C3 reflect liver fibrosis and liver function in HIV positive patients receiving modern cART

Leona Dold, Mette J Nielsen, Michael Praktiknjo, Carolynne Schwarze-Zander, Christoph Boesecke, Robert Schierwagen, Raphael Mohr, Jan-Christian Wasmuth, Christian Jansen, Jenny Bischoff, Jürgen Kurt Rockstroh, Morten A Karsdal, Ulrich Spengler, Jonel Trebicka, Diana J Leeming

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Resumé

BACKGROUND AND AIMS: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSION: 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.

OriginalsprogEngelsk
Artikelnummere0219526
TidsskriftPLOS ONE
Vol/bind14
Udgave nummer7
Antal sider12
ISSN1932-6203
DOI
StatusUdgivet - 2019

Fingeraftryk

liver cirrhosis
liver function
Liver Cirrhosis
Liver
HIV
collagen
liver
Collagen Type III
fibrosis
extracellular matrix
Liver Diseases
portal hypertension
Collagen Type IV
degradation
blood platelet count
bilirubin
Portal Hypertension
liver diseases
Platelet Count
Collagen

Citer dette

Dold, L., Nielsen, M. J., Praktiknjo, M., Schwarze-Zander, C., Boesecke, C., Schierwagen, R., ... Leeming, D. J. (2019). Circulating levels of PRO-C3 reflect liver fibrosis and liver function in HIV positive patients receiving modern cART. PLOS ONE, 14(7), [e0219526]. https://doi.org/10.1371/journal.pone.0219526
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. / Circulating levels of PRO-C3 reflect liver fibrosis and liver function in HIV positive patients receiving modern cART. I: PLOS ONE. 2019 ; Bind 14, Nr. 7.
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title = "Circulating levels of PRO-C3 reflect liver fibrosis and liver function in HIV positive patients receiving modern cART",
abstract = "BACKGROUND AND AIMS: 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.METHODS: 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.RESULTS: 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.CONCLUSION: 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.",
author = "Leona Dold and Nielsen, {Mette J} and Michael Praktiknjo and Carolynne Schwarze-Zander and Christoph Boesecke and Robert Schierwagen and Raphael Mohr and Jan-Christian Wasmuth and Christian Jansen and Jenny Bischoff and Rockstroh, {J{\"u}rgen Kurt} and Karsdal, {Morten A} and Ulrich Spengler and Jonel Trebicka and Leeming, {Diana J}",
year = "2019",
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language = "English",
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Dold, L, Nielsen, MJ, Praktiknjo, M, Schwarze-Zander, C, Boesecke, C, Schierwagen, R, Mohr, R, Wasmuth, J-C, Jansen, C, Bischoff, J, Rockstroh, JK, Karsdal, MA, Spengler, U, Trebicka, J & Leeming, DJ 2019, 'Circulating levels of PRO-C3 reflect liver fibrosis and liver function in HIV positive patients receiving modern cART', PLOS ONE, bind 14, nr. 7, e0219526. https://doi.org/10.1371/journal.pone.0219526

Circulating levels of PRO-C3 reflect liver fibrosis and liver function in HIV positive patients receiving modern cART. / 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.

I: PLOS ONE, Bind 14, Nr. 7, e0219526, 2019.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Circulating levels of PRO-C3 reflect liver fibrosis and liver function in HIV positive patients receiving modern cART

AU - Dold, Leona

AU - Nielsen, Mette J

AU - Praktiknjo, Michael

AU - Schwarze-Zander, Carolynne

AU - Boesecke, Christoph

AU - Schierwagen, Robert

AU - Mohr, Raphael

AU - Wasmuth, Jan-Christian

AU - Jansen, Christian

AU - Bischoff, Jenny

AU - Rockstroh, Jürgen Kurt

AU - Karsdal, Morten A

AU - Spengler, Ulrich

AU - Trebicka, Jonel

AU - Leeming, Diana J

PY - 2019

Y1 - 2019

N2 - BACKGROUND AND AIMS: 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.METHODS: 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.RESULTS: 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.CONCLUSION: 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.

AB - BACKGROUND AND AIMS: 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.METHODS: 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.RESULTS: 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.CONCLUSION: 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.

U2 - 10.1371/journal.pone.0219526

DO - 10.1371/journal.pone.0219526

M3 - Journal article

VL - 14

JO - P L o S One

JF - P L o S One

SN - 1932-6203

IS - 7

M1 - e0219526

ER -