Biomarkers of liver fibrosis: Clinical translation of molecular pathogenesis or based on liver-dependent malfunction tests

Background: Fibrosis is the excessive deposition and histological redistribution of extracellular matrix (ECM) in the tissue as consequence of chronic liver damage. It leads to progressive liver insufficiency, portal hypertension and ultimately to cirrhosis and primary liver cell carcinoma. There is a strong demand for reliable, organ- and disease-specific, non-invasive biomarkers of fibrosis and fibrogenesis to replace or to complement the invasive method of needle biopsy, which is afflicted with a high degree of sampling error. Methods: A systematic literature search was performed using electronic databases and reference lists of relevant publications to ascertain studies with non-invasive biomarkers of liver fibrosis. Results: Two classes of serum biomarkers can be differentiated: Class I markers are those, which reflect ECM turnover (fibrogenesis and fibrolysis) and/or fibrogenic cell changes, mainly of hepatic stellate cells, which are. the dominant profibrogenic cell type in liver. They are mostly cost intensive, single laboratory tests and derive from the translation of fibrogenic mechanisms into clinical application. Examples are procollagen peptides, hyaluronan, and laminin. Class II biomarkers are based on algorithmic evaluation of commonly observed functional alterations of the liver that do not necessarily reflect ECM metabolism and/or fibrogenic cell changes. About 20 numerical scores or indices are reported for parameters, which are mostly routine laboratory tests and frequently multiparametric (panels). Among them fibrotest, hepascore, ELF-score have reached limited clinical application. Conclusions: Up to now the impact of both classes of biomarkers for diagnosis and monitoring of fibrosis, fibrogenesis, and fibrolysis is limited. They cannot replace needle biopsy but some of them might be complementary in follow-up studies. Innovative methods like proteomics and glycomics to establish fibrosis-specific serum protein and glycosylation patterns, respectively, might have a high potential for diagnosis and monitoring of fibrogenesis. (c) 2007 Elsevier B.V. All rights reserved.