INCREASED INTERCELLULAR-ADHESION MOLECULE-1 SERUM CONCENTRATION IN CHOLESTASIS

Background/Aims: Increase of serum levels of the soluble intercelluar adhesion molecules in patients with the cholestatic liver diseases pri mary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are known and have been thought to indicate activation of the immune s ystem and the grade of the inflammatory process. In hepatitis and chol estatic diseases, expression of adhesion molecules was found on the su rface of bile duct epithelia and hepatocytes. Materials and Methods: S erum levels of sICAM-1 in patients with intrahepatic cholestasis in PB C (n=42) and extrahepatic cholestasis (n=18) due to choledocholithiasi s were investigated. sICAM-1 levels and ''classical'' cholestasis para meters as alkaline phosphatase (ALP), gamma-glutamyl-transpeptidase (g amma-GTP) and bilirubin levels were compared. Furthermore, sICAM-1 con centrations and ''classical'' cholestasis parameters were analysed bef ore and after therapy with ursodeoxycholic acid (UDCA). In addition, s ICAM-1 was detected in serum and bile fluid of four patients with chol estasis due to choledocholithiasis. Soluble ICAM-1 levels in sera and, if accessible, in bile fluids were determined using a commercially av ailable ELISA system. Statistics were done by Wilcoxon's signed rank e xact test and Spearman's rank correlation test. Sensitivity and specif icity of cholestasis parameters and sICAM-1 concentrations was analyse d by receiver operating characteristic (ROC) curves. Results: Increase d sICAM-1 serum concentrations in a similar range were found in patien ts with PBC (range 251-2620 mu g/l; median 966 mu g/l) as well as in p atients with extrahepatic cholestasis (257-2961 mu g/l; median 760 mu g/l) compared to healthy controls (n=12; 220-500 mu g/l; median 318 mu g/l) sICAM-1 levels correlated significantly to histological stage I to IV (p<0.001), ALP (range 107-1877 U/l; median 545 U/l; r=0.496, p=0 .0008), bilirubin (range 0.3-26 mg/dl; median 0.8 mg/dl; r=0.52; p<0.0 004) and gamma-GTP levels (range 43-705 U/l; median 221 U/l; r=0.36; p =0.02) in PBC patients. In PBC patients a histological stage III or ni (n=21) could be predicted with high sensitivity (95%) and specificity (85%) if sICAM-1 levels were above 840 mu g/l. After treatment of PBC patients with UDCA, sICAM-1 levels decreased significantly with decli ne of other ''classical'' cholestasis parameters. Increased sICAM-1 le vels (range 257-2961, median 745 mu g/l) in extrahepatic cholestasis c orrelated also significantly with serum concentrations of bilirubin (r =0.8; p<0.01; range 0.3-19.7, median 1.6 mg/dl), gamma-GTP (r=0.55; p= 0.03; range 33-1401, median 179 U/l) and ALP (r=0.61; p=0.1; range 110 -1378, median 562 U/l). sICAM-1 was detectable in bile fluid (264-919 mu g/l) of four patients with extrahepatic cholestasis and nose-biliar y catheterisation. Conclusions: sICAM-1 concentrations were found to d iscriminate between histological stage I/II and stage III/IV of PBC wi th higher sensitivity and specificity than ''classical'' cholestasis p arameters. Increased serum concentrations for sICAM-1 in intra- and in eirtrahepatic cholestasis and detection of sICAM-1 in the bile may in dicate that sICAM-1 is eliminated through the bile. In other words, no t only increased synthesis but also decreased elimination may be respo nsible for increased sICAM-1 serum levels in patients with cholestatic liver diseases.