Serological markers of extracellular matrix remodeling predict transplant‐free survival in primary sclerosing cholangitis

Abstract

Extracellular matrix remodeling is elevated in primary sclerosing cholangitis patients compared to ulcerative colitis patients. Furthermore, the interstitial matrix marker PRO-C3 was identified as a potent prognostic marker and an independent predictor of transplant-free survival in primary sclerosing cholangitis.

Collagen biology and non‐invasive biomarkers of liver fibrosis

“…PRO‐C3 has been demonstrated to be highly related to fibrosis stage and disease activity across various CLD aetiologies . Within cross‐sectional NAFLD studies, PRO‐C3 was shown to perform well when separating patients with advanced fibrosis from those without (AUROC 0.81, 0.74) .…”

“…In both studies, significant changes in PRO‐C3 level from baseline were observed as a result of therapy . There are limited studies regarding the predictive value of PRO‐C3; however, studies have shown that PRO‐C3 has the ability to predict decompensation and mortality in patients with liver disease, and to predict transplant‐free survival in patients with PSC . However, further investigation regarding the predictive and prognostic value of PRO‐C3 is required, as well as its relationship to clinical outcomes.…”

“…PRO-C3 has been demonstrated to be highly related to fibrosis stage and disease activity across various CLD aetiologies. 75,76,112,113 Within cross-sectional NAFLD studies, PRO-C3 was shown to perform well when separating patients with advanced fibrosis from those without (AUROC 0.81, 0.74). 76,112 to be optimal for the identification of patients with advanced liver fibrosis (sens 84%, spec 75%, PPV 46% and NPV 95%).…”

“…however, studies have shown that PRO-C3 has the ability to predict decompensation and mortality in patients with liver disease, 116 and to predict transplant-free survival in patients with PSC. 113 However, further investigation regarding the predictive and prognostic value of PRO-C3 is required, as well as its relationship to clinical outcomes.…”

Emerging therapies in primary sclerosing cholangitis: pathophysiological basis and clinical opportunities

“…A specific marker of collagen III formation Associated with clinical outcome (LTX or death) in a single center study [193] Showed change at 12 weeks of treatment in a phase II study on NGM282, indicating dynamic potential [107] PRO-C3 directly reflects collagen III formation, which is an important part of fibrogenesis and hence the pathogenesis of PSC, and a therapeutic target…”