Plasma Pro‐C3 (N‐terminal type III collagen propeptide) predicts fibrosis progression in patients with chronic hepatitis C

Abstract Background & Aims Fibrogenesis results in release of certain extracellular matrix protein fragments into the circulation. We evaluated the diagnostic and prognostic performance of two novel serological markers, the precisely cleaved N‐terminal propeptide of type III collagen (Pro‐C3) and a peptide of helical collagen type III degradation (C3M), in chronic hepatitis C ( CHC ) patients. Method Pro‐C3 and C3M were measured by ELISA in plasma from CHC patients ( n = 194) from a prior phase II antifibrotic trial ( NCT 00244751). Plasma samples and paired liver biopsies were obtained at baseline and after 1‐year. Patients were stratified according to Ishak stages 2‐4. Internal cross‐validation was performed by bootstrap analysis. Results Pro‐C3 levels were significantly higher in CHC patients in Ishak stage 4 compared to stage 2 ( P < 0.001) or 3 ( P < 0.01). Pro‐C3 could significantly distinguish moderate (stage 4) from mild fibrosis (stage 2/3) ( AUC = 0.72, P < 0.001). Importantly, an overall significance in Pro‐C3 ( P = 0.007) levels was observed between the groups of −1, 0, +1 and +2 change in Ishak stage at 12 months. Pro‐C3 was significantly increased in group +1 ( P = 0.030) and +2 ( P = 0.021) compared to group 0. No significant differences were observed for C3M. In multivariate analysis, only baseline Pro‐C3, but not FibroTest, had an independent association with fibrosis progression. Conclusions Pro‐C3 is a useful test to predict fibrogenesis and monitor disease progression. Moreover, it could differentiate mild from moderate disease. Pro‐C3 may become a promising blood parameter be included in future studies for monitoring disease progression and eventually for evaluation of potential antifibrotic therapies.