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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine I, University of Bonn, Bonn, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Jansen
authors.affiliation: Nordic Bioscience, Fibrosis Biology and Biomarkers, Herlev, Denmark.
authors.forename: Diana J
authors.initials: DJ
authors.lastname: Leeming
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Mattias
authors.initials: M
authors.lastname: Mandorfer
authors.affiliation: Nordic Bioscience, Fibrosis Biology and Biomarkers, Herlev, Denmark.
authors.forename: Inger
authors.initials: I
authors.lastname: Byrjalsen
authors.affiliation: Department of Internal Medicine I, University of Bonn, Bonn, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Schierwagen
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Philipp
authors.initials: P
authors.lastname: Schwabl
authors.affiliation: Nordic Bioscience, Fibrosis Biology and Biomarkers, Herlev, Denmark.
authors.forename: Morten A
authors.initials: MA
authors.lastname: Karsdal
authors.affiliation: Department of Internal Medicine I, University of Bonn, Bonn, Germany.
authors.forename: Evrim
authors.initials: E
authors.lastname: Anadol
authors.affiliation: Department of Internal Medicine I, University of Bonn, Bonn, Germany.
authors.forename: Christian P
authors.initials: CP
authors.lastname: Strassburg
authors.affiliation: Department of Internal Medicine I, University of Bonn, Bonn, Germany; German Centre for Infection Research (DZIF), partner site Bonn-Cologne, Bonn, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Rockstroh
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Peck-Radosavljevic
authors.affiliation: Center of Functional and Diagnostic Imaging and Research, Department of Clinical Physiology, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Møller
authors.affiliation: Gastro Unit, Medical Division, Hvidovre Hospital, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Flemming
authors.initials: F
authors.lastname: Bendtsen
authors.affiliation: Department of Medical Gastroenterology, Odense University Hospital, Odense, Denmark.
authors.forename: Aleksander
authors.initials: A
authors.lastname: Krag
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Reiberger
authors.affiliation: Department of Internal Medicine I, University of Bonn, Bonn, Germany.
authors.forename: Jonel
authors.initials: J
authors.lastname: Trebicka
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D060085:Coinfection / Q000097:blood / Q000276:immunology; D003176:Complement C3 / Q000276:immunology*; D003181:Complement C4 / Q000276:immunology; D003182:Complement C5 / Q000276:immunology; D005109:Extracellular Matrix / Q000473:pathology; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000276:immunology; D006801:Humans; D006975:Hypertension, Portal; D008099:Liver / Q000293:injuries; D008103:Liver Cirrhosis / Q000097:blood* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D017082:Portal Pressure; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D003176:Complement C3; D003181:Complement C4; D003182:Complement C5; D000410:Alanine Transaminase