PRO-C3-levels in patients with HIV/HCV-Co-infection reflect fibrosis stage and degree of portal hypertension

Christian Jansen; Diana J Leeming; Mattias Mandorfer; Inger Byrjalsen; Robert Schierwagen; Philipp Schwabl; Morten A Karsdal; Evrim Anadol; Christian P Strassburg; Jürgen Rockstroh; Markus Peck-Radosavljevic; Søren Møller; Flemming Bendtsen; Aleksander Krag; Thomas Reiberger; Jonel Trebicka

doi:10.1371/journal.pone.0108544

PRO-C3-levels in patients with HIV/HCV-Co-infection reflect fibrosis stage and degree of portal hypertension

Christian Jansen, Diana J Leeming, Mattias Mandorfer, Inger Byrjalsen, Robert Schierwagen, Philipp Schwabl, Morten A Karsdal, Evrim Anadol, Christian P Strassburg, Jürgen Rockstroh, Markus Peck-Radosavljevic, Søren Møller, Flemming Bendtsen, Aleksander Krag, Thomas Reiberger, Jonel Trebicka

Department of Clinical Medicine

24 Citations (Scopus)

Abstract

BACKGROUND: Liver-related deaths represent the leading cause of mortality among patients with HIV/HCV-co-infection, and are mainly related to complications of fibrosis and portal hypertension. In this study, we aimed to evaluate the structural changes by the assessment of extracellular matrix (ECM) derived degradation fragments in peripheral blood as biomarkers for fibrosis and portal hypertension in patients with HIV/HCV co-infection.

METHODS: Fifty-eight patients (67% male, mean age: 36.5 years) with HIV/HCV-co-infection were included in the study. Hepatic venous pressure gradient (HVPG) was measured in forty-three patients. The fibrosis stage was determined using FIB4 -Score. ECM degraded products in peripheral blood were measured using specific ELISAs (C4M, MMP-2/9 degraded type IV collagen; C5M, MMP-2/9 degraded type V collagen; PRO-C3, MMP degraded n-terminal propeptide of type III collagen).

RESULTS: As expected, HVPG showed strong and significant correlations with FIB4-index (rs = 0.628; p = 7*10-7). Interestingly, PRO-C3 significantly correlated with HVPG (rs = 0.354; p = 0.02), alanine aminotransferase (rs = 0.30; p = 0.038), as well as with FIB4-index (rs = 0.3230; p = 0.035). C4M and C5M levels were higher in patients with portal hypertension (HVPG>5 mmHg).

CONCLUSION: PRO-C3 levels reflect liver injury, stage of liver fibrosis and degree of portal hypertension in HIV/HCV-co-infected patients. Furthermore, C4M and C5M were associated with increased portal pressure. Circulating markers of hepatic ECM remodeling might be helpful in the diagnosis and management of liver disease and portal hypertension in patients with HIV/HCV coinfection.

Original language	English
Article number	e108544
Journal	PloS one
Volume	9
Issue number	9
Pages (from-to)	1-7
Number of pages	7
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0108544
Publication status	Published - 29 Sept 2014

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Jansen, C., Leeming, D. J., Mandorfer, M., Byrjalsen, I., Schierwagen, R., Schwabl, P., Karsdal, M. A., Anadol, E., Strassburg, C. P., Rockstroh, J., Peck-Radosavljevic, M., Møller, S., Bendtsen, F., Krag, A., Reiberger, T., & Trebicka, J. (2014). PRO-C3-levels in patients with HIV/HCV-Co-infection reflect fibrosis stage and degree of portal hypertension. PloS one, 9(9), 1-7. Article e108544. https://doi.org/10.1371/journal.pone.0108544

Jansen, C, Leeming, DJ, Mandorfer, M, Byrjalsen, I, Schierwagen, R, Schwabl, P, Karsdal, MA, Anadol, E, Strassburg, CP, Rockstroh, J, Peck-Radosavljevic, M, Møller, S , Bendtsen, F, Krag, A, Reiberger, T & Trebicka, J 2014, 'PRO-C3-levels in patients with HIV/HCV-Co-infection reflect fibrosis stage and degree of portal hypertension', PloS one, vol. 9, no. 9, e108544, pp. 1-7. https://doi.org/10.1371/journal.pone.0108544

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title = "PRO-C3-levels in patients with HIV/HCV-Co-infection reflect fibrosis stage and degree of portal hypertension",

abstract = "BACKGROUND: Liver-related deaths represent the leading cause of mortality among patients with HIV/HCV-co-infection, and are mainly related to complications of fibrosis and portal hypertension. In this study, we aimed to evaluate the structural changes by the assessment of extracellular matrix (ECM) derived degradation fragments in peripheral blood as biomarkers for fibrosis and portal hypertension in patients with HIV/HCV co-infection.METHODS: Fifty-eight patients (67% male, mean age: 36.5 years) with HIV/HCV-co-infection were included in the study. Hepatic venous pressure gradient (HVPG) was measured in forty-three patients. The fibrosis stage was determined using FIB4 -Score. ECM degraded products in peripheral blood were measured using specific ELISAs (C4M, MMP-2/9 degraded type IV collagen; C5M, MMP-2/9 degraded type V collagen; PRO-C3, MMP degraded n-terminal propeptide of type III collagen).RESULTS: As expected, HVPG showed strong and significant correlations with FIB4-index (rs = 0.628; p = 7*10-7). Interestingly, PRO-C3 significantly correlated with HVPG (rs = 0.354; p = 0.02), alanine aminotransferase (rs = 0.30; p = 0.038), as well as with FIB4-index (rs = 0.3230; p = 0.035). C4M and C5M levels were higher in patients with portal hypertension (HVPG>5 mmHg).CONCLUSION: PRO-C3 levels reflect liver injury, stage of liver fibrosis and degree of portal hypertension in HIV/HCV-co-infected patients. Furthermore, C4M and C5M were associated with increased portal pressure. Circulating markers of hepatic ECM remodeling might be helpful in the diagnosis and management of liver disease and portal hypertension in patients with HIV/HCV coinfection.",

author = "Christian Jansen and Leeming, {Diana J} and Mattias Mandorfer and Inger Byrjalsen and Robert Schierwagen and Philipp Schwabl and Karsdal, {Morten A} and Evrim Anadol and Strassburg, {Christian P} and J{\"u}rgen Rockstroh and Markus Peck-Radosavljevic and S{\o}ren M{\o}ller and Flemming Bendtsen and Aleksander Krag and Thomas Reiberger and Jonel Trebicka",

year = "2014",

month = sep,

day = "29",

doi = "10.1371/journal.pone.0108544",

language = "English",

volume = "9",

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TY - JOUR

T1 - PRO-C3-levels in patients with HIV/HCV-Co-infection reflect fibrosis stage and degree of portal hypertension

AU - Jansen, Christian

AU - Leeming, Diana J

AU - Mandorfer, Mattias

AU - Byrjalsen, Inger

AU - Schierwagen, Robert

AU - Schwabl, Philipp

AU - Karsdal, Morten A

AU - Anadol, Evrim

AU - Strassburg, Christian P

AU - Rockstroh, Jürgen

AU - Peck-Radosavljevic, Markus

AU - Møller, Søren

AU - Bendtsen, Flemming

AU - Krag, Aleksander

AU - Reiberger, Thomas

AU - Trebicka, Jonel

PY - 2014/9/29

Y1 - 2014/9/29

N2 - BACKGROUND: Liver-related deaths represent the leading cause of mortality among patients with HIV/HCV-co-infection, and are mainly related to complications of fibrosis and portal hypertension. In this study, we aimed to evaluate the structural changes by the assessment of extracellular matrix (ECM) derived degradation fragments in peripheral blood as biomarkers for fibrosis and portal hypertension in patients with HIV/HCV co-infection.METHODS: Fifty-eight patients (67% male, mean age: 36.5 years) with HIV/HCV-co-infection were included in the study. Hepatic venous pressure gradient (HVPG) was measured in forty-three patients. The fibrosis stage was determined using FIB4 -Score. ECM degraded products in peripheral blood were measured using specific ELISAs (C4M, MMP-2/9 degraded type IV collagen; C5M, MMP-2/9 degraded type V collagen; PRO-C3, MMP degraded n-terminal propeptide of type III collagen).RESULTS: As expected, HVPG showed strong and significant correlations with FIB4-index (rs = 0.628; p = 7*10-7). Interestingly, PRO-C3 significantly correlated with HVPG (rs = 0.354; p = 0.02), alanine aminotransferase (rs = 0.30; p = 0.038), as well as with FIB4-index (rs = 0.3230; p = 0.035). C4M and C5M levels were higher in patients with portal hypertension (HVPG>5 mmHg).CONCLUSION: PRO-C3 levels reflect liver injury, stage of liver fibrosis and degree of portal hypertension in HIV/HCV-co-infected patients. Furthermore, C4M and C5M were associated with increased portal pressure. Circulating markers of hepatic ECM remodeling might be helpful in the diagnosis and management of liver disease and portal hypertension in patients with HIV/HCV coinfection.

AB - BACKGROUND: Liver-related deaths represent the leading cause of mortality among patients with HIV/HCV-co-infection, and are mainly related to complications of fibrosis and portal hypertension. In this study, we aimed to evaluate the structural changes by the assessment of extracellular matrix (ECM) derived degradation fragments in peripheral blood as biomarkers for fibrosis and portal hypertension in patients with HIV/HCV co-infection.METHODS: Fifty-eight patients (67% male, mean age: 36.5 years) with HIV/HCV-co-infection were included in the study. Hepatic venous pressure gradient (HVPG) was measured in forty-three patients. The fibrosis stage was determined using FIB4 -Score. ECM degraded products in peripheral blood were measured using specific ELISAs (C4M, MMP-2/9 degraded type IV collagen; C5M, MMP-2/9 degraded type V collagen; PRO-C3, MMP degraded n-terminal propeptide of type III collagen).RESULTS: As expected, HVPG showed strong and significant correlations with FIB4-index (rs = 0.628; p = 7*10-7). Interestingly, PRO-C3 significantly correlated with HVPG (rs = 0.354; p = 0.02), alanine aminotransferase (rs = 0.30; p = 0.038), as well as with FIB4-index (rs = 0.3230; p = 0.035). C4M and C5M levels were higher in patients with portal hypertension (HVPG>5 mmHg).CONCLUSION: PRO-C3 levels reflect liver injury, stage of liver fibrosis and degree of portal hypertension in HIV/HCV-co-infected patients. Furthermore, C4M and C5M were associated with increased portal pressure. Circulating markers of hepatic ECM remodeling might be helpful in the diagnosis and management of liver disease and portal hypertension in patients with HIV/HCV coinfection.

U2 - 10.1371/journal.pone.0108544

DO - 10.1371/journal.pone.0108544

M3 - Journal article

C2 - 25265505

SN - 1932-6203

VL - 9

SP - 1

EP - 7

JO - PloS one

JF - PloS one

IS - 9

M1 - e108544

ER -

PRO-C3-levels in patients with HIV/HCV-Co-infection reflect fibrosis stage and degree of portal hypertension

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