Pro-C5, a marker of true type V collagen formation and fibrillation, correlates with portal hypertension in patients with alcoholic cirrhosis

Scand J Gastroenterol. 2015 May;50(5):584-92. doi: 10.3109/00365521.2014.996590. Epub 2015 Feb 1.


Background and aims: The hepatic venous pressure gradient (HVPG) is an important but invasive diagnostic and prognostic marker in cirrhotic patients. The aim of the study was to evaluate a novel biochemical plasma marker of true type V collagen formation (Pro-C5) for describing HVPG.

Methods: Ninety-four patients mainly with alcoholic cirrhosis and fourteen liver-healthy controls were included in a retrospective study. Relevant clinical and routine laboratory data and hemodynamics were determined. Plasma Pro-C5 was correlated to HVPG and liver function parameters. Furthermore, Pro-C5 was combined in a linear regression model.

Results: Plasma Pro-C5 correlated to HVPG, indocyanine green clearance, sustained vascular resistance and mean arterial pressure (r = -0.68-0.33, p < 0.0001). A multiple regression analysis including Pro-C5, alanine aminotransferase, bilirubin and model for end-stage liver disease (MELD) improved the correlation to HVPG (r = 0.74, p < 0.0001). Plasma Pro-C5 was positively or negatively correlated to a number of routine liver function markers and MELD score (r = 0.27-0.68; p < 0.05-0.0001). Furthermore, plasma Pro-C5 could clearly separate patients with a HVPG <10 mmHg or HVPG ≥10 mmHg (p < 0.001, area under the curve (AUC) = 0.73), HVPG 10-<16 mmHg or HVPG ≥16 mmHg (p < 0.001, AUC = 0.68) and controls from diseased patients (p < 0.0001, AUC = 0.88). Finally, there was a clear relation to increasing Child score A-C and plasma Pro-C5 (ANOVA p < 0.001).

Conclusion: Plasma Pro-C5 reflects liver hemodynamics, liver function, disease stage and clinically significant portal hypertension (PH). A multimarker model in combination with clinical scores predicted HVPG and separated clinical relevant HVPG thresholds. Plasma Pro-C5 may be suitable for the noninvasive evaluation of PH in patients with cirrhosis.

Keywords: biochemical marker; cirrhosis; clinic; liver; noninvasive.; portal hypertension.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alanine Transaminase / blood
  • Area Under Curve
  • Bilirubin / blood
  • Biomarkers / blood
  • Collagen Type V / chemistry*
  • Complement C5 / chemistry*
  • End Stage Liver Disease / complications*
  • Female
  • Humans
  • Hypertension, Portal / diagnosis*
  • Linear Models
  • Liver Cirrhosis, Alcoholic / complications
  • Liver Cirrhosis, Alcoholic / diagnosis*
  • Male
  • Middle Aged
  • ROC Curve
  • Retrospective Studies


  • Biomarkers
  • Collagen Type V
  • Complement C5
  • Alanine Transaminase
  • Bilirubin