Gressner Olav A, Weiskirchen Ralf, Gressner Axel M
Institute of Clinical Chemistry and Pathobiochemistry, RWTH-University Hospital, Central Laboratory, Pauwelsstr. 30, 52074 Aachen, Germany.
Clin Chim Acta. 2007 Jun;381(2):107-13. doi: 10.1016/j.cca.2007.02.038. Epub 2007 Feb 27.
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.
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.
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.
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.
纤维化是由于慢性肝损伤导致细胞外基质（ECM）在组织中过度沉积和组织学重新分布。它会导致进行性肝功能不全、门静脉高压，并最终发展为肝硬化和原发性肝细胞癌。迫切需要可靠的、器官和疾病特异性的、非侵入性的纤维化和纤维生成生物标志物，以替代或补充存在高度抽样误差的侵入性肝穿刺活检方法。
通过电子数据库和相关出版物的参考文献列表进行系统的文献检索，以确定有关肝纤维化非侵入性生物标志物的研究。
可区分两类血清生物标志物：I类标志物是那些反映ECM周转（纤维生成和纤维溶解）和/或纤维生成细胞变化的标志物，主要是肝星状细胞的变化，肝星状细胞是肝脏中主要的促纤维化细胞类型。它们大多成本高昂，是单一实验室检测项目，源自将纤维生成机制转化为临床应用。例如前胶原肽、透明质酸和层粘连蛋白。II类生物标志物基于对肝脏常见功能改变的算法评估，这些改变不一定反映ECM代谢和/或纤维生成细胞变化。报告了约20种数值评分或指数用于相关参数，这些参数大多是常规实验室检测项目，且通常是多参数的（组合检测）。其中，FibroTest、Hepascore、ELF评分已在有限范围内应用于临床。
到目前为止，这两类生物标志物在纤维化、纤维生成和纤维溶解的诊断和监测方面的作用有限。它们不能替代肝穿刺活检，但其中一些可能在随访研究中具有辅助作用。分别用于建立纤维化特异性血清蛋白和糖基化模式的蛋白质组学和糖组学等创新方法，在纤维生成的诊断和监测方面可能具有很大潜力。
