3.
Laboratory parameters included in multi-parameter scores (panels) and their potential pathogenetic link to fibrogenesis/fibrosis
| Parameter | Potential pathobiochemical basis | |||
|---|---|---|---|---|
| Platelets (thrombocytes) | • | Impaired synthesis due to reduced thrombopoietin production in diseased liver | ||
| • | Enhanced consumption in chronically inflamed liver by disseminated intravascular coagulation or immune mechanisms | |||
| • | Increased destruction in enlarged spleen, shortening of platelet life time | |||
| Prothrombin time (partially activated thromboplastin time) | • | Measures activity/concentration of hepatogenic coagulation factors 1, 2, 5, 8–12, indicators of liver cell protein synthesis | ||
| • | Prolongation due to decreased production in liver cell insufficiency | |||
| Aspartate aminotransferase (AST) | • | Parameter of liver cell necrosis (and apoptosis ?) | ||
| • | Leakage from cytosol and mitochondria into blood stream | |||
| Alanine aminotransferase (ALT) | • | Parameter of liver cell necrosis (and apoptosis ?) | ||
| • | Leakage from cytosol into sinusoidal blood stream | |||
| γ-glutamyltransferase (γGT) | • | Sensitive parameter of hepatobiliary diseases (cholestasis) | ||
| • | Induction by abuse of alcohol (ethanol) and certain drugs | |||
| Pseudo-cholinesterase (PCHE) | • | Liver (hepatocyte)-specific enzyme | ||
| • | Parameter of anabolic liver cell insufficiency | |||
| Bilirubin | • | Degradation product of haemoglobin removed by hepatocytes | ||
| • | Parameter of hepato-biliary diseases | |||
| α2-macroglobulin | • | High molecular mass glycoprotein synthesized in hepatocytes, which serves as | ||
| • | proteinase inhibitor and scavenger protein, acute-phase-protein | |||
| • | Binds TGF-β, CTGF(?) and other cytokines, involved in their clearance from circulation by hepatocytes | |||
| Hyaluronan (hyaluronic acid) | • | Unsulfated, protein-free, highly polymerized glycosoaminoglycan, component of fibrotic matrix, synthesized by activated hepatic stellate cells | ||
| • | Important endogeneous ligand for Toll-like receptor TLR-4 of Kupffer cells and hepatic stellate cells | |||
| Cholesterol | • | Impaired synthesis in hepatocytes by HMG-CoA-reductase in advanced liver insufficiency, no obvious link to fibrogenesis | ||
| Apolipoprotein A-I | • | Component of HDL, up-regulation in and secretion by activated hepatic stellate cells, expression in hepatocytes, no obvious link to fibrogenesis | ||
| Aminoterminal pro-peptide of type III pro-collagen (PIIINP) | • | Increased production of the N-terminal split product of type III pro-collagen during fibrogenesis | ||
| Tissue inhibitor of metallo-proteinases (TIMP-1) | • | Up-regulation in fibrotic liver and in activated hepatic sellate cells, promotes progression of fibrosis through inhibition of matrix degradation | ||
| N-acetyl-β, D-glucosaminidase (β-NAG) | • | Increased activity in liver and serum in acute and chronic-active liver injury, correlation with the grade of fibrogenic activity | ||
| Haptoglobin | • | In hepatocytes synthesized acute-phase-protein, indicates inflammation but unspecific, scavenger protein for hemoglobin, antioxidans, no obvious link to fibrogenesis | ||
| HOMA, insulin resistance index | • | Hyperinsulinemia (insulin resistance) is associated with rapid fibrosis progression in HCV, insulin stimulates hepatic stellate cells to collagen synthesis, glucose up-regulates CTGF/CCN2 and TGF-β | ||
| Fibronectin | • | Matrix-associated plasma protein, increased expression in fibrotic conditions, up-regulation in activated hepatic stellate cells | ||
| Matrix metallo-proteinase-1 (MMP-1) | • | Proteolytic enzyme involved in degradation, turnover and re-modelling of extracellular matrix | ||