Plasma Pro-C3 (N-terminal type III collagen propeptide) predicts fibrosis progression in patients with chronic hepatitis C
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Plasma Pro-C3 (N-terminal type III collagen propeptide) predicts fibrosis progression in patients with chronic hepatitis C. / Nielsen, Mette J.; Veidal, Sanne S.; Karsdal, Morten A.; Ørsnes-Leeming, Diana J.; Vainer, Ben; Gardner, Stephen D.; Hamatake, Robert; Goodman, Zachary D.; Schuppan, Detlef; Patel, Keyur.
In: Liver International, Vol. 35, No. 2, 02.2015, p. 429-437.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Plasma Pro-C3 (N-terminal type III collagen propeptide) predicts fibrosis progression in patients with chronic hepatitis C
AU - Nielsen, Mette J.
AU - Veidal, Sanne S.
AU - Karsdal, Morten A.
AU - Ørsnes-Leeming, Diana J.
AU - Vainer, Ben
AU - Gardner, Stephen D.
AU - Hamatake, Robert
AU - Goodman, Zachary D.
AU - Schuppan, Detlef
AU - Patel, Keyur
N1 - © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
PY - 2015/2
Y1 - 2015/2
N2 - 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 (NCT00244751). 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.
AB - 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 (NCT00244751). 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.
KW - Biomarkers
KW - Cohort Studies
KW - Collagen Type III
KW - Disease Progression
KW - Enzyme-Linked Immunosorbent Assay
KW - Hepatitis C, Chronic
KW - Humans
KW - Liver Cirrhosis
KW - Multivariate Analysis
KW - Predictive Value of Tests
U2 - 10.1111/liv.12700
DO - 10.1111/liv.12700
M3 - Journal article
C2 - 25308921
VL - 35
SP - 429
EP - 437
JO - Liver International
JF - Liver International
SN - 1478-3223
IS - 2
ER -
ID: 160023157