ADAPT: An Algorithm Incorporating PRO‐C3 Accurately Identifies Patients With NAFLD and Advanced Fibrosis

Abstract

PRO-C3 is an independent predictor of fibrosis stage in NAFLD. A PRO-C3 based score (ADAPT) accurately identifies patients with NAFLD and advanced fibrosis and is superior to APRI, FIB-4 and NFS. This article is protected by copyright. All rights reserved.

Improvement of non‐invasive markers of NAFLD from an individualised, web‐based exercise program

“…PRO‐C3 is an emerging, dynamic biomarker of fibrillar collagen formation by fibroblasts in the process of depositing the core fibrosis structure, in which the main composition is the impermeable collagen fibrosis structure of the newly formed intestinal matrix . On the other hand, type IV collagen turnover quantified by C4M2, is part of the loose permeable basement membrane underlying the hepatocytes which have been suggested to part of a natural repair response and part of beneficial remodelling of the basement membrane, are increasingly used to predict hepatic fibrosis . While there was no change during the initial 8‐week intervention period, these markers improved over the 20‐week follow‐up indicating that a decrease in non‐invasive markers of hepatic inflammation and beneficial metabolic changes may translate into delayed improvement of non‐invasive measures of fibrosis, potentially through de‐activation of fibroblasts in NASH.…”

“…Activated types of fibroblasts produce type III collagen in a dense interstitial matrix, which may be quantified by the N‐terminal pro‐peptide of type III collagen (PIIINP) PRO‐C3. PRO‐C3 is released into serum during ECM formation and has emerged as a non‐invasive biomarker of fibrogenesis, correlating with the severity of liver fibrosis in NAFLD by itself and in compound surrogate scores, as well as being prognostic for fibrosis progression . A different ECM is produced by hepatocytes, the basement membrane, which undergoes remodelling and has been implicated in repair response .…”

Collagen biology and non‐invasive biomarkers of liver fibrosis

“…Hence, serum biomarkers that directly target components of the ECM scar have a distinct advantage over indirect biomarkers and scores, such as ALT, AST and FIB‐4, in that they more accurately reflect the dynamics of the fibrotic processes. The relationship of biomarkers targeting a range of collagens and pro‐peptides of collagens to the severity of liver fibrosis has been investigated in a variety of diseases and has shown promise as potential non‐invasive diagnostics . At present, the most validated and accurate biomarkers for the measurement of type III collagen formation are the N‐terminal propeptide PIIINP and PRO‐C3 biomarkers (Figure ).…”

Reading the stars for hepatic fibrosis or how to predict the severity of liver disease in patients with NASH

“…Additionally, the variability of transaminases—reflecting hepatic inflammation—appears to be limiting to the concept that a surrogate score containing these could predict fibrosis development over a short time, during which structural tissue remodelling has not yet occurred. To overcome the shortcoming of transaminases in predicting hepatic fibrosis, a recent study introduced a marker of type III collagen, PRO‐C3, in a four variables containing non‐invasive surrogate score for the prediction of advanced fibrosis (age, presence of diabetes, platelets, PRO‐C3) eliminating AST/ALT ratio and albumin . This score achieved comparable accuracy to the NFS in a cross‐sectional cohort.…”