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

PLoS One. 2014 Sep 29;9(9):e108544. doi: 10.1371/journal.pone.0108544. eCollection 2014.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alanine Transaminase / blood
  • Coinfection / blood
  • Coinfection / immunology
  • Complement C3 / immunology*
  • Complement C4 / immunology
  • Complement C5 / immunology
  • Extracellular Matrix / pathology
  • Female
  • HIV Infections / blood*
  • HIV Infections / immunology
  • Hepatitis C, Chronic / blood*
  • Hepatitis C, Chronic / immunology
  • Humans
  • Hypertension, Portal*
  • Liver / injuries
  • Liver Cirrhosis / blood*
  • Liver Cirrhosis / immunology
  • Male
  • Middle Aged
  • Portal Pressure
  • Retrospective Studies
  • Young Adult


  • Complement C3
  • Complement C4
  • Complement C5
  • Alanine Transaminase

Grants and funding

This work was supported by: 1. Deutsche Forschungsgemeinschaft (SFB TRR57 P18 to Jonel Trebicka); 2. J. & W. Hector-Foundation (to Jonel Trebicka); 3. unrestricted research grants from Roche Austria (to Markus Peck-Radosavljevic); 4. MSD Austria (to Markus Peck-Radosavljevic); 5. DZIF TTU HIV Project 05.803; 6. German Center for Infection Research (DZIF); 7. Danish Science Foundation; and 8. Danish Ministry of Science and Technology. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.