Potential novel biomarkers for monitoring the fibrogenic process in liver

The clinical course of chronic liver diseases is significantly dependent on the progression rate of fibrosis, that is, the unstructured replacement of injured parenchyma by extracellular matrix. Fibrogenesis (i.e., the development of fibrosis) can be regarded as an unlimited wound-healing process, which is based on matrix synthesis in activated hepatic stellate cells, fibroblasts and, potentially, by hepatocytes and biliary epithelial cells converted to (myo-)fibroblasts. Blood biomarkers of fibrogenesis and fibrosis can be divided into class I and class II. Class I biomarkers are single tests, which are based on the pathophysiology of fibrosis, whereas class II biomarkers are mostly multiparametric algorithms, which have been statistically evaluated with regard to the detection and follow-up of fibrosis. None of the presently available approach fulfils the criteria of an ideal test, but increased understanding of the pathogenesis of fibrosis offers additional ways for pathophysiologically well-based biomarkers. These include transforming growth factor (TGF)-β-driven marker proteins, bone-marrow-derived cells (fibrocytes) and cytokines, which govern pro- and anti-fibrotic activities. Proteomic and glycomic approaches of serum are under investigation to set up specific protein profiles in patients with liver fibrosis. These and other novel parameters will supplement liver biopsy/histology, high-resolution imaging analysis and elastography for the detection and monitoring of patients with liver fibrosis.