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Serologic extracellular matrix remodeling markers are related to fibrosis stage and prognosis in a phase 2b trial of simtuzumab in patients with primary sclerosing cholangitis.

Publication ,  Journal Article
Thorburn, D; Leeming, DJ; Barchuk, WT; Wang, Y; Lu, X; Malkov, VA; Ito, KL; Bowlus, CL; Levy, C; Goodman, Z; Karsdal, MA; Muir, AJ; Xu, J
Published in: Hepatol Commun
July 1, 2024

BACKGROUND: Novel noninvasive predictors of disease severity and prognosis in primary sclerosing cholangitis (PSC) are needed. This study evaluated the ability of extracellular matrix remodeling markers to diagnose fibrosis stage and predict PSC-related fibrosis progression and clinical events. METHODS: Liver histology and serum markers of collagen formation (propeptide of type III collagen [Pro-C3], propeptide of type IV collagen, propeptide of type V collagen), collagen degradation (type III collagen matrix metalloproteinase degradation product and type IV collagen matrix metalloproteinase degradation product), and fibrosis (enhanced liver fibrosis [ELF] score and its components [metalloproteinase-1, type III procollagen, hyaluronic acid]) were assessed in samples from baseline to week 96 in patients with PSC enrolled in a study evaluating simtuzumab (NCT01672853). Diagnostic performance for advanced fibrosis (Ishak stages 3-6) and cirrhosis (Ishak stages 5-6) was evaluated by logistic regression and AUROC. Prognostic performance for PSC-related clinical events and fibrosis progression was assessed by AUROC and Wilcoxon rank-sum test. RESULTS: Among 234 patients, 51% had advanced fibrosis and 11% had cirrhosis at baseline. Baseline Pro-C3 and ELF score and its components provided moderate diagnostic ability for discrimination of advanced fibrosis (AUROC 0.73-0.78) and cirrhosis (AUROC 0.73-0.81). Baseline Pro-C3, ELF score, and type III procollagen provided a moderate prognosis for PSC-related clinical events (AUROC 0.70-0.71). Among patients without cirrhosis at baseline, median changes in Pro-C3 and ELF score to week 96 were higher in those with than without progression to cirrhosis (both p < 0.001). CONCLUSIONS: Pro-C3 correlated with fibrosis stage, and Pro-C3 and ELF score provided discrimination of advanced fibrosis and cirrhosis and predicted PSC-related events and fibrosis progression. The results support the clinical utility of Pro-C3 and ELF score for staging and as prognostic markers in PSC.

Duke Scholars

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Published In

Hepatol Commun

DOI

EISSN

2471-254X

Publication Date

July 1, 2024

Volume

8

Issue

7

Location

United States

Related Subject Headings

  • Severity of Illness Index
  • Prognosis
  • Middle Aged
  • Male
  • Liver Cirrhosis
  • Liver
  • Hyaluronic Acid
  • Humans
  • Female
  • Extracellular Matrix
 

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Thorburn, D., Leeming, D. J., Barchuk, W. T., Wang, Y., Lu, X., Malkov, V. A., … Xu, J. (2024). Serologic extracellular matrix remodeling markers are related to fibrosis stage and prognosis in a phase 2b trial of simtuzumab in patients with primary sclerosing cholangitis. Hepatol Commun, 8(7). https://doi.org/10.1097/HC9.0000000000000467
Thorburn, Douglas, Diana J. Leeming, William T. Barchuk, Ya Wang, Xiaomin Lu, Vladislav A. Malkov, Kaori L. Ito, et al. “Serologic extracellular matrix remodeling markers are related to fibrosis stage and prognosis in a phase 2b trial of simtuzumab in patients with primary sclerosing cholangitis.Hepatol Commun 8, no. 7 (July 1, 2024). https://doi.org/10.1097/HC9.0000000000000467.
Thorburn D, Leeming DJ, Barchuk WT, Wang Y, Lu X, Malkov VA, Ito KL, Bowlus CL, Levy C, Goodman Z, Karsdal MA, Muir AJ, Xu J. Serologic extracellular matrix remodeling markers are related to fibrosis stage and prognosis in a phase 2b trial of simtuzumab in patients with primary sclerosing cholangitis. Hepatol Commun. 2024 Jul 1;8(7).

Published In

Hepatol Commun

DOI

EISSN

2471-254X

Publication Date

July 1, 2024

Volume

8

Issue

7

Location

United States

Related Subject Headings

  • Severity of Illness Index
  • Prognosis
  • Middle Aged
  • Male
  • Liver Cirrhosis
  • Liver
  • Hyaluronic Acid
  • Humans
  • Female
  • Extracellular Matrix