Collagen biology and non‐invasive biomarkers of liver fibrosis

Abstract

There is an unmet need for high‐quality liquid biomarkers that can safely and reproducibly predict the stage of fibrosis and the outcomes of chronic liver disease (CLD). The requirement for such markers has intensified because of the high global prevalence of diseases such as non‐alcoholic fatty liver disease (NAFLD). In particular, there is a need for diagnostic and prognostic tools, as well as predictive biomarkers that reflect the efficacy of interventions, as described by the BEST criteria (Biomarkers, EndpointS, and other Tools Resource). This review covers the various liver collagens, their functional role in tissue homeostasis and delineates the common nomenclature for biomarkers based on BEST criteria. It addresses the common confounders affecting serological biomarkers, and describes defined collagen epitope biomarkers that originate from the dynamic processes of extracellular matrix (ECM) remodelling during liver injury.

Erythropoietin-Modified Mesenchymal Stem Cells Enhance Anti-fibrosis Efficacy in Mouse Liver Fibrosis Model

“…5A). The typical characteristics of hepatic fibrosis are the activation of HSC and excessive deposition of ECM 3 . As a unique marker of HSC activation, a-SMA is positively correlated with proliferation of HSCs and degree of liver fibrosis [28].…”

“…Studies show that the common pathological basis of many chronic liver diseases is liver fibrosis [2]. Liver fibrosis is an intermediate process of transformation from a variety of chronic liver diseases to liver cirrhosis, which is mainly characterized by the activation of hepatic stellate cells (HSCs) and excessive deposition of extracellular matrix (ECM) [3,4]. However, ideal drugs for the treatment of liver fibrosis are lacking.…”

Clinical assessment and management of liver fibrosis in non-alcoholic fatty liver disease

“…Other direct markers of liver fibrosis are collagens and their fragments since they represent the principal component of the fibrotic scars. The most validated biomarkers for the measurement of type III collagen formation are the amino-terminal propeptide of procollagen type III (PIIINP) and N-terminal pro-collagen III peptide (PRO-C3) biomarkers[ 46 ]. PRO-C3 which is a collagen fragment is significantly higher in NASH patients with advanced fibrosis than those without advanced fibrosis.…”

Elucidating Potential Profibrotic Mechanisms of Emerging Biomarkers for Early Prognosis of Hepatic Fibrosis

“…Apart from being invasive, the liver biopsy also have several limitations including, patient discomfort, considerable cost of treatment, prolonged hospitalizations and minimal risk of complications such as peritoneal bleeding. Furthermore, there may be sampling variation, poor sample quality, inter- and intra-observer variability and the possibility of error in small biopsy samples which may not reflect the fibrotic changes occurring in the entire liver [ 22 , 23 , 24 , 26 ]. Therefore, alternate strategies are required to supplant liver biopsy since it is not practical and affordable to biopsy each patient.…”