Affiliations: Department of Pharmacology, Nordic Bioscience,
Herlev, Denmark | Novartis Pharma AG Translational Medicine, Basel,
Switzerland | Department of Pathology, Rigshospitalet,
University of Copenhagen, Denmark
Abstract: Background: Fibrosis is a central histological feature of chronic
liver diseases and is characterized by the accumulation and reorganization of
the extracellular matrix. The gold standard for assessment of fibrosis is
histological evaluation of a percutaneous liver biopsy. Albeit a considerable
effort have been invested in finding alternative non-invasive approaches, these
have not been sufficiently succesfull to replace biopsy assessment. Aim: To identify the extracellular matrix proteins of interest, that as protein
degradation fragments produced during extracellular matrix metabolism
neo-epitopes, may be targeted for novel biochemical marker development in
fibrosis. We used the recently proposed BIPED system (Burden of disease,
Investigative, Prognostic, Efficacy and Diagnostic) to
characterise present serological markers. Methods: Pubmed was search for
keywords; Liver fibrosis, neo-epitopes, biomarkers, clinical trail, extra
cellular matrix, protease, degradation, fragment. Results and Conclusion: Implementation of BIPED categorization in the development and validation of
fibrosis biomarkers to simplify and standardize the use of existing and future
biomarkers seems advantageous. In addition, a systematic use of the neo-epitope
approach, i.e. the quantification of peptide epitopes generated from enzymatic
cleavage of proteins during extracellular remodeling, may prove productive in
the quest to find new markers of liver fibrosis.
